Unitedhealthcare West HMO Signaturevalue Prior Authorization Guidelines for Non-Specialty Pharmacy Drugs

Home , Clascoterone, Diabetes and pregnancy, Pipamazine, Rapacuronium bromide, Rimexolone

UnitedHealthcare West HMO SignatureValue Prior Authorization Guidelines for Non-Specialty Pharmacy Drugs

Table of Contents

5HT-1 Receptor Agonists (Triptans) ...... 7 Abilify MyCite (aripiprazole tablet with sensor) - PA/Med Nec ...... 11 Absorica, Absorica LD (isotretinoin) - PA/Med Nec ...... 16 Addyi (flibanserin) - PA/Med Nec ...... 20 Afrezza (insulin human) - PA/Med Nec ...... 24 Albuterol HFA, ProAir HFA, Proventil HFA - NonFormulary or Step Therapy ...... 28 Albuterol Tablets - PA/Med Nec ...... 30 Amitiza (lubiprostone) - PA/Med Nec ...... 34 Amzeeq (minocycline 4% topical foam) - PA Med/Nec ...... 40 Angiotensin Receptor Blockers ...... 43 Anthelmintics - PA/Med Nec ...... 46 Anti-Influenza Agents ...... 54 Anticonvulsants - Banzel (rufinamide), Diacomit (stiripentol), Nayzilam (midazolam), Sabril (vigabatrin), Sympazan (clobazam), Valtoco (diazepam) ...... 70 Anticonvulsants - Single Source Brand - PA/Med Nec ...... 77 Anticonvulsants - Step Therapy ...... 83 Antidepressants - Step Therapy ...... 87 Antiemetics Quantity Limit Overrides...... 90 Antipsoriatic Agents ...... 97 Apidra (insulin glulisine) ...... 105 Asacol HD (mesalamine tablet, delayed-release) and Delzicol (mesalamine capsule, delayed-release) - NonFormulary or Step Therapy ...... 110 Atelvia (risedronate delayed-release) ...... 113 Azole Antifungals ...... 116 Basal Insulin ...... 125 Belbuca (buprenorphine hydrochloride film) and Butrans (buprenorphine patch, extended-release) - PA/Med Nec ...... 127 Benznidazole ...... 135 Blood Glucose Test Strips ...... 138 Bonjesta (doxylamine/pyridoxine extended-release), Diclegis (doxylamine/pyridoxine delayed release) - PA/Med Nec ...... 144

Page 1 BPH Agents ...... 147 Breast Cancer Prevention Zero Dollar Cost Share - generic tamoxifen (applies to 20mg dose only) and generic raloxifene, generic aromatase inhibitors (anastrozole, letrozole, or exemestane) ...... 149 Bronchitol (mannitol) ...... 153 Caduet (amlodipine/atorvastatin) ...... 156 Caplyta (lumateperone) - PA/Med Nec ...... 159 Cetraxal (ciprofloxacin otic suspension) ...... 162 CGRP Antagonists - PA/Med Nec ...... 164 CNS Stimulants ...... 173 Colchicine Tablet (Colcrys authorized generic) ...... 177 Compounds and Bulk Powders ...... 180 Contraceptives ...... 190 Corlanor (ivabradine) ...... 192 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (OR, WA, TX) ...... 196 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (UHC of CA) ...... 199 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (UHC of OK) ...... 202 Daliresp (roflumilast) ...... 208 DAW Override ...... 211 Devices ...... 215 Diabetes Medications - SGLT2 Inhibitors - Step Therapy...... 220 Diabetic Agents ...... 227 Dihydroergotamine nasal spray (Migranal), Ergomar (ergotamine) ...... 230 Dihydroergotamine nasal spray (Migranal), Ergomar (ergotamine) - PA/Med Nec ...... 234 Dojolvi (triheptanoin) - PA/Med Nec ...... 238 Doxepin Cream - PA/Med Nec ...... 242 DPP4 Inhibitors - Step Therapy - All ASO, Non-NY Fully Insured, Non-NJ Fully Insured, and Non-CT Fully Insured ...... 245 Dry Eye Disease – PA/Med Nec ...... 249 Dulera (mometasone furoate/formoterol fumarate) - Step Therapy ...... 254 Duopa (carbidopa/levodopa) - PA/Med Nec ...... 257 Elidel (pimecrolimus), Protopic (tacrolimus) - Step Therapy ...... 260 Elmiron (pentosan polysulfate sodium) - Step Therapy ...... 263 Endari (L-glutamine Powder for Solution) - PA/Med Nec ...... 266 Enspryng (satralizumab-mwge) - PA/Med Nec ...... 269

Page 2 Entresto (valsartan-sacubitril) - PA/Med Nec ...... 274 Erectile Dysfunction Agents ...... 279 Eucrisa (crisaborole) - Step Therapy ...... 285 Exforge (amlodipine/valsartan), Exforge HCT (amlodipine/valsartan/HCTZ) ...... 289 Extina (ketoconazole) – Step Therapy ...... 291 Fanapt (iloperidone), Fanapt Pack (iloperidone), Vraylar (cariprazine) - Step Therapy ...... 294 Fentanyl Transmucosal ...... 298 Fiasp (insulin aspart) - Nonformulary ...... 307 Fibric Acid Derivatives ...... 310 Flurazepam ...... 312 Fortamet (metformin extended-release, brand and generic), Glucophage XR (metformin extended- release, brand only) and Glumetza (metformin extended-release, brand and generic) - PA/Med Nec ...... 315 Glaucoma Agents - Step Therapy ...... 321 GLP-1 Receptor Agonists ...... 324 Glucovance ...... 328 Gonococcal Ophthalmia Neonatorum (GON) Prevention Zero Dollar Cost Share ...... 332 Gralise, Gralise Starter Pack - Step Therapy ...... 335 Health Care Reform - Cardiovascular Disease Prevention Zero Cost Share ...... 337 Healthcare Reform (HCR) Exceptions ...... 340 High Dollar/Claim Dollar ...... 347 HIV Pre-exposure Prophylaxis (PrEP) Zero Dollar Cost Share – California – Descovy and generic tenofovir disoproxil fumarate 300 mg ...... 356 HIV Pre-exposure Prophylaxis (PrEP) Zero Dollar Cost Share – generic tenofovir disoproxil fumarate 300 mg ...... 358 Impavido (miltefosine) ...... 361 Ingrezza (valbenazine) - PA/Med Nec ...... 364 Inhaled Corticosteroids ...... 368 Invokana (canagliflozin) - NonFormulary ...... 371 Iron Chelators...... 375 Kapvay (clonidine) extended-release ...... 381 Ketek (Telithromycin) ...... 383 Ketoprofen and Ketoprofen ER - Step Therapy ...... 388 Klisyri (tirbanibulin) - Step Therapy ...... 391

Page 3 Lampit (nifurtimox) ...... 394 Levemir (insulin detemir) ...... 397 Lidoderm (Lidocaine Patch 5%) and ZTLido (lidocaine topical system) ...... 400 Lidoderm (Lidocaine Patch), ZTLido ...... 404 Linzess (linaclotide), Symproic (naldemedine) ...... 407 Lithobid (lithium carbonate) - PA/Med Nec ...... 410 Lokelma (sodium zirconium cyclosilicate), Veltassa (patiromer) - PA/Med Nec ...... 413 Long-Acting Opioids ...... 417 Lonhala Magnair (glycopyrrolate inhalation solution), Yupelri (revefenacin inhalation solution) - PA/Med Nec ...... 429 Lotronex (alosteron) - Notification ...... 434 Lucemyra (lofexidine) - PA/Med Nec ...... 437 Lyrica CR (pregabalin) - Step Therapy ...... 440 MEDcDUR - Opioid Overutilization Cumulative Drug Utilization Review Criteria (including individual long-acting opioid supply limits) ...... 444 Meglitinides and Meglitinide Combination Agents ...... 458 Migraine Quantity Limit ...... 460 Minocycline extended-release tablet (generic Solodyn), Minolira (minocycline extended-release tablet), Solodyn (minocycline extended-release tablet), Ximino (minocycline extended-release capsule) ...... 466 Mirvaso (brimonidine gel), Rhofade (oxymetazoline cream) ...... 470 Motegrity (prucalopride) - PA/Med Nec ...... 473 Movantik (naloxegol) - PA/Med Nec ...... 477 Multaq (dronedarone) ...... 480 Multisource Brand Anticonvulsants ...... 483 Mytesi (crofelemer) ...... 489 Nexletol (bempedoic acid) and Nexlizet (bempedoic acid/ezetimibe) - PA/Med Nec ...... 492 Nocdurna (desmopressin acetate)- PA/Med Nec ...... 498 Non-Solid Oral Dosage Forms ...... 502 Non-steroidal Anti-Inflammatory Agents ...... 506 NonFormulary Exception Process ...... 511 Nourianz (istradefylline) - PA/Med Nec ...... 513 Nucynta (tapentadol), Tramadol-containing Products ...... 516 Nuedexta (dextromethorphan/quinidine) – PA/Med Nec ...... 522

Page 4 Nuplazid (pimavanserin tartrate) ...... 525 Nurtec ODT (rimegepant), Ubrelvy (ubrogepant) - PA/Med Nec ...... 528 Ophthalmic Anti-Allergic Agents ...... 535 Ophthalmic Corticosteroids (Alrex, Lotemax, Vexol) ...... 539 Opioid Dependence ...... 546 Opioid-containing cough medicines (including: Flowtuss, Hycofenix, Obredon, Tuzistra XR, Tussionex, Tussicaps, Tuxarin ER, Zutripo, codeine/phenylephrine/promethazine, codeine/promethazine, hydrocodone/homatropine, hydrocodone bitartrate/guaifenesin) - PA/Med Nec ...... 549 Oriahnn (elagolix and estradiol/norethindrone) - PA/Med Nec ...... 552 Osphena (ospemifene) ...... 556 Overactive Bladder Agents ...... 559 Oxistat (oxiconazole) cream - PA/Med Nec ...... 561 Pancreatic Enzyme Products (PEPs) - Step Therapy ...... 564 Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel- PA/Med Nec ...... 567 Praluent (alirocumab) - PA/Med Nec ...... 570 Premenstrual Dysphoric Disorder Agents (Sarafem, Selfemra) ...... 580 Prevpac (lansoprazole, amoxicillin and clarithromycin) ...... 582 Progesterone Products ...... 585 Proton Pump Inhibitors ...... 590 Provigil (modafinil) and Nuvigil (armodafinil) ...... 599 Quantity Limit General ...... 602 Regranex (becaplermin gel) ...... 606 Relistor (methylnaltrexone bromide) - PA/Med Nec ...... 609 Repatha (evolocumab) - PA/Med Nec ...... 614 Rexulti (brexpiprazole) - PA/Med Nec ...... 625 Rexulti (brexpiprazole) - Step Therapy ...... 631 Reyvow (lasmiditan) - PA/Med Nec ...... 636 Sedative Hypnotic Agents - Step Therapy ...... 641 Selzentry (maraviroc) ...... 645 Sensipar (cinacalcet) - PA/Med Nec ...... 647 Short-Acting Opioid Review Criteria for opioid naïve members ...... 651 Silenor (doxepin) ...... 660 Slynd (drospirenone) - PA/Med Nec ...... 662 Solaraze (diclofenac 3% gel) ...... 666

Page 5 Solosec (secnidazole) - Step Therapy ...... 668 Sprix (ketorolac) - Step Therapy...... 671 Statins - NonFormulary and Step Therapy ...... 674 Sublingual Immunotherapy (SLIT) - PA/Med Nec ...... 677 Sunosi (solriamfetol) ...... 687 Symlin (pramlintide acetate injection)...... 691 Tasmar (tolcapone) - PA/Med Nec ...... 694 Temodar (temozolomide) ...... 698 Topical Androgens ...... 708 Topical Antifungals - PA/Med Nec ...... 718 Topical Retinoid Products ...... 721 Tresiba (insulin degludec) ...... 727 Trulance (plecanatide), Zelnorm (tegaserod) - PA/Med Nec ...... 729 Uloric (febuxostat) - Step Therapy ...... 733 Ultravate - Step Therapy ...... 736 Upneeq (oxymetazoline) - PA/Med Nec ...... 739 Vascepa (icosapent ethyl)* - PA/Med Nec ...... 743 Vecamyl (mecamylamine) ...... 750 Veregen (sinecatechins) - Step Therapy ...... 753 Verquvo (vericiguat) – PA/Med Nec ...... 755 Viberzi (eluxadoline) - PA/Med Nec ...... 760 Vyleesi (bremelanotide) - PA/Med Nec ...... 763 Weight Loss Agents - Prior Authorization - California, Maryland, and New York Regulatory Program 767 Winlevi (clascoterone) - PA/Med Nec ...... 778 Xifaxan (rifaximin) - PA/Med Nec ...... 782 Zileuton extended-release (generic Zyflo CR) , Zyflo (zileuton) - Step Therapy ...... 789 Zilxi (minocycline) ...... 792 Zomig (zolmitriptan) nasal spray - Step Therapy ...... 795

Page 6 5HT-1 Receptor Agonists (Triptans)

Prior Authorization Guideline

GL-33280 5HT-1 Receptor Agonists (Triptans)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 2/13/1998; P&T Revision Date: 5/19/2016

1 . Indications Drug Name: Amerge (naratriptan), Frova (frovatriptan), Imitrex (sumatriptan), Relpax (eletriptan), Zomig (zolmitriptan) tablets, Zomig-ZMT (zolmitriptan orally disintegrating tablets) Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults. Not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness have not been established for cluster headache, which is present in an older, predominantly male population.

Drug Name: Axert (almotriptan) Migraine Headaches for adults Indicated for the acute treatment of migraine with or without aura in adults.

Page 7

Migraine Headaches for adolescents Indicated for adolescents, age 12 to 17 years, for the acute treatment of migraine headache pain in patients with a history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated). Important Limitations: Only use where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Axert, the diagnosis of migraine should be reconsidered before Axert is administered to treat any subsequent attacks. In adolescents age 12 to 17 years, efficacy of Axert on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. Axert is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of Axert have not been established for cluster headache which is present in an older, predominantly male population.

Drug Name: Maxalt (rizatriptan), Maxalt-MLT (rizatriptan orally disintegrating tablets) Migraine headaches Indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old. Limitations of Use: •Maxalt should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Maxalt, the diagnosis of migraine should be reconsidered before Maxalt is administered to treat any subsequent attacks. •Maxalt is not indicated for use in the management of hemiplegic or basilar migraine •Maxalt is not indicated for the prevention of migraine attacks. •Safety and effectiveness of Maxalt have not been established for cluster headache.

Drug Name: Treximet (sumatriptan/naproxen) Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older. Limitations of use: Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with Treximet, reconsider the diagnosis of migraine before Treximet is administered to treat any subsequent attacks. Treximet is not indicated for the prevention of migraine attacks. Safety and effectiveness of Treximet have not been established for cluster headache.

Drug Name: Zecuity (sumatriptan succinate, extended-release patch) Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with Zecuity reconsider the diagnosis of migraine before Zecuity is administered to treat any subsequent attacks. Zecuity is not intended for the prevention of migraine attacks.

Drug Name: Zomig Nasal Spray (zolmitriptan) Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older. Limitations of Use: Only use Zomig if a clear diagnosis of migraine has been established. If a patient has no response to Zomig treatment for the first migraine attack, reconsider the diagnosis of migraine before Zomig is administered to treat any subsequent attacks. Zomig is not indicated for the prevention of migraine attacks. Safety and effectiveness of Zomig have not been established for cluster

Page 8 headache. Not recommended in patients with moderate or severe hepatic impairment

2 . Criteria

Product Name: Generic almotriptan, Brand Amerge, Brand Axert, Frova, Generic naratriptan, or Relpax Guideline Type Non Formulary

Approval Criteria

1 - Diagnosis of migraine headaches with or without aura

AND

2 - History of failure, contraindication or intolerance to three formulary 5-HT1 receptor agonist (triptan) alternatives [e.g., Imitrex (sumatriptan), Maxalt/Maxalt-MLT (rizatriptan), Zomig/Zomig- ZMT (zolmitriptan)]

Product Name: Onzetra, Treximet, Zecuity Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following:

• Rizatriptan/rizatriptan ODT • Sumatriptan tablets/nasal spray • Zolmitriptan/zolmitriptan ODT

3 . Background

Benefit/Coverage/Program Information

Page 9 Quantity Limit These products are subject to an OptumRx standard quantity limit. The quantity limit may vary from the standard limit based upon plan-specific benefit design. Please refer to your benefit materials.

4 . References

1. Amerge Prescribing Information. GlaxoSmithKline, February 2013. 2. Axert Prescribing Information. Ortho-McNeil Pharmaceutical, Inc. September, 2011 3. Frova Prescribing Information. Endo Pharmaceuticals, Inc., February 2013. 4. Relpax Prescribing Information. Pfizer, Inc. June 2012. 5. Treximet Prescribing Information. GlaxoSmithKline, May 2016. 6. Zecuity iontophoretic transdermal system Prescribing Information. Teva Pharmaceuticals. August 2015. 7. Onzetra prescribing information. Aliso Viejo, CA. Avanir Pharmaceuticals, Inc. January 2016.

Page 10 Abilify MyCite (aripiprazole tablet with sensor) - PA/Med Nec

Prior Authorization Guideline

GL-90388 Abilify MyCite (aripiprazole tablet with sensor) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 1/16/2019 P&T Revision Date: 04/15/2020 ; 6/16/2021

1 . Indications Drug Name: Abilify MyCite (aripiprazole tablet with sensor) Schizophrenia, Bipolar I disorder, Major depressive disorder Indicated for the treatment of schizophrenia, bipolar I disorder, and as adjunctive treatment for major depressive disorder.

2 . Criteria

Product Name: Abilify MyCite* Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 11

Approval Criteria

1 - Diagnosis of one of the following:

• schizophrenia • bipolar I disorder • major depressive disorder • autistic disorder • Tourette’s disorder

AND

2 - Submission of medical records documenting the patient is currently prescribed aripiprazole and tolerates the medication.

AND

3 - Submission of medical records documenting the patient’s adherence to aripiprazole is less than 80% within the past 6 months (medication adherence percentage is defined as the number of pills absent in a given time period divided by the number of pills prescribed during that same time, multiplied by 100).

AND

4 - All of the following strategies (if applicable to the patient) to improve patient adherence have been tried without success:

• Utilization of a pill box. • Utilization of a smart phone reminder (ex. alarm, application, or text reminder). • Involving family members or friends to assist. • Coordinating timing of dose to coincide with dosing of another daily medication.

AND

5 - Submission of medical records documenting patient has experienced life-threatening or potentially life-threatening symptoms, or has experienced a severe worsening of symptoms leading to a hospitalization which was attributed to the lack of adherence to aripiprazole.

Page 12 AND

6 - History of failure, contraindication, or intolerance to one long-acting injectable antipsychotic (e.g. Abilify Maintena, Risperdal Consta, Invega Trinza)

AND

7 - Prescriber acknowledges that Abilify MyCite has not been shown to improve patient adherence and attests that Abilify MyCite is medically necessary for the patient to maintain compliance, avoid life-threatening worsening of symptoms, and reduce healthcare resources utilized due to lack of adherence.

AND

8 - Prescriber agrees to track and document adherence of Abilify MyCite through software provided by the manufacturer. Notes *Abilify MyCite is typically excluded from coverage.

Product Name: Abilify MyCite* Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation that patient is clinically stable on Abilify MyCite.

AND

2 - Submission of medical records documenting that the use of Abilify MyCite has increased adherence to 80% or more.

AND

3 - Prescriber attests that the patient requires the continued use of Abilify MyCite to remain

Page 13 adherent. Notes *Abilify MyCite is typically excluded from coverage.

3 . Background

Benefit/Coverage/Program Information

Background:

Abilify MyCite (aripiprazole tablet with sensor)* is a drug-device combination product comprised of aripiprazole tablets embedded with a sensor intended to track drug ingestion. Abilify MyCite is indicated for the treatment of schizophrenia, bipolar I disorder, and as adjunctive treatment for major depressive disorder. Abilify MyCite has not been shown to improve patient adherence and should not be used to track real-time ingestion during an emergency as the detection may be delayed or may not occur.

Additional Clinical Rules:

4 . References

1. Abilify MyCite [package insert]. Rockville, MD: Otsuka Pharmaceuticals, Inc; February 2020. 2. Levenson, JL. (2018). Psychological factors affecting other medical conditions: Management. D. Solomon (Ed.), UpToDate. Retrieved February 21, 2020. 3. Cramer, JA et al. Medication Compliance and Persistence: Terminology and Definitions. Value in Health, January 2008; 11(1):44-47. 4. Brown, MT at al. Mediation Adherence: WHO Cares? May Clin Proc. April 2011; 86(4):304-314.

5 . Revision History

Date Notes

Page 14 7/26/2021 Annual review. Updated references.

Page 15 Absorica, Absorica LD (isotretinoin) - PA/Med Nec

Prior Authorization Guideline

GL-77816 Absorica, Absorica LD (isotretinoin) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/4/2020 P&T Approval Date: 12/19/2018 P&T Revision Date: 12/18/2019 ; 05/15/2020

1 . Indications Drug Name: Absorica, Absorica LD (isotretinoin) Acne Indicated for the treatment of severe recalcitrant nodular acne.

2 . Criteria

Product Name: Absorica*, Absorica LD* (isotretinoin) Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 16 Approval Criteria

1 - Submission of medical records documenting one of the following:

1.1 Diagnosis of severe recalcitrant nodular acne unresponsive to conventional therapy

1.2 Diagnosis of treatment resistant acne

AND

2 - History of failure, contraindication, or intolerance to an adequate trial of two of the following conventional therapy regimens

2.1 Topical retinoid or retinoid-like agent [e.g.,Retin-A/Retin-A Micro (tretinoin),]

2.2 Oral antibiotic [e.g., Ery-Tab (erythromycin), Minocin (minocycline)]

2.3 Topical antibiotic with or without benzoyl peroxide [eg, Cleocin-T (clindamycin), erythromycin, BenzaClin (benzoyl peroxide/clindamycin), Benzamycin (benzoyl peroxide/erythromycin)]

AND

3 - History of failure, contraindication, or intolerance to an adequate trial on two oral isotretinoin formulations (document duration of trial):

• Claravis • Myorisan • Zenatane • Amnesteem

Notes *Absorica and Absorica LD are typically excluded from benefit coverag

Page 17 e

Product Name: Absorica*, Absorica LD* (isotretinoin) Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Absorica or Absorica LD will be approved for continuation of therapy based on submission of medical records documenting ONE of the following criterion:

1.1 After greater than or equal to 2 months off therapy, persistent or recurring severe recalcitrant nodular acne is still present

1.2 Total cumulative dose for total duration of therapy is less than 150 mg/kg (will be approved up to a total up 150 mg/kg) Notes *Absorica and Absorica LD are typically excluded from benefit coverag e

3 . Background

Benefit/Coverage/Program Information

Background:

Isotretinoin is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or more. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Isotretinoin should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. Due to its teratogenicity, isotretinoin is not indicated in females who are or may become pregnant.

A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it is recommended to wait at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off isotretinoin. The optimal interval

Page 18 before retreatment has not been defined for patients who have not completed skeletal growth.

4 . References

1. Absorica [Package Insert] Jacksonville, FL: Ranbaxy Laboratories Inc.;May 2018. 2. Absorica LD[Package Insert] Jacksonville, FL: Ranbaxy Laboratories Inc.; January 2020.

5 . Revision History

Date Notes

12/3/2020 Corrected error in reauthorization language.

Page 19 Addyi (flibanserin) - PA/Med Nec

Prior Authorization Guideline

GL-61377 Addyi (flibanserin) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 3/1/2020 P&T Approval Date: 9/3/2015 P&T Revision Date: 12/18/2019

1 . Indications Drug Name: Addyi (flibanserin) Generalized hypoactive sexual desire disorder (HSDD) Indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner. Addyi is not indicated for the treatment of HSDD in postmenopausal women or in men and is not indicated to enhance sexual performance.

2 . Criteria

Page 20 Product Name: Addyi Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of one of the following:

1.1 Acquired, generalized hypoactive sexual desire disorder (HSDD)

1.2 Female sexual interest/arousal disorder

AND

2 - Symptoms of HSDD or female sexual interest/arousal disorder have persisted for at least 6 months

AND

3 - Low sexual desire is NOT due to any of the following:

• A co-existing medical or psychiatric condition • Problems within the relationship • The effects of a medication or other drug substance

AND

4 - Patient was female at birth

AND

5 - Patient is premenopausal

Page 21

AND

6 - Patient does not have hepatic impairment (e.g., a Child-Pugh score of 6 points or greater)

AND

7 - Patient is not concomitantly on moderate or strong CYP3A4 inhibitors (e.g., ciprofloxacin, clarithromycin, diltiazem, fluconazole, itraconazole, ketoconazole, ritonavir, verapamil)

Product Name: Addyi Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Addyi therapy

AND

2 - Patient continues to be premenopausal

AND

3 - Patient does not have hepatic impairment (e.g., a Child-Pugh score of 6 points or greater)

AND

4 - Patient is not concomitantly on moderate or strong CYP3A4 inhibitors (eg, ciprofloxacin, clarithromycin, diltiazem, fluconazole, itraconazole, ketoconazole, ritonavir, verapamil)

Page 22 3 . Background

Benefit/Coverage/Program Information

Background:

Addyi is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner. Addyi is not indicated for the treatment of HSDD in postmenopausal women or in men and is not indicated to enhance sexual performance.

Additional Clinical Rules: • Supply limits may be in place • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class

4 . References

1. Addyi Prescribing Information. Sprout Pharmaceuticals, Inc. Raleigh, NC. October 2019. 2. Thorp J, Simon J, Dattani D, et al. Treatment of Hypoactive Sexual Desire Disorder in Premenopausal Women: Efficacy of Flibanserin in the DAISY Study. J Sex Med 2012;9:793-804. 3. Katz M, DeRogatis LR, Ackerman R, et al. Efficacy of Flibanserin in Women with Hypoactive Sexual Desire Disorder: Results from the BEGONIA Trial. J Sex Med 2013;10:1807-1815. 4. DeRogatis LR, Komer L, Katz M, et al. Treatment of Hypoactive Sexual Desire Disorder in Premenopausal Women: Efficacy of Flibanserin in the VIOLET Study. J Sex Med 2012;9:1074-1085 5. Sexual dysfunctions. In: Diagnostic and Statistical Manual of Mental Disorders, 5th ed., American Psychiatric Association, Arlington, Virginia 2013. 6. Sexual dysfunction in women: Management. UpToDate. Updated April 14, 2017. Last accessed April 6, 2018. 7. Addyi Risk Evaluation and Mitigation Stategy (REMS) Program information. https://www.addyirems.com/AddyiUI/rems/home.action. Last accessed May 7, 2019.

Page 23 Afrezza (insulin human) - PA/Med Nec

Prior Authorization Guideline

GL-68954 Afrezza (insulin human) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2020 P&T Approval Date: 7/14/2015 P&T Revision Date: 6/17/2020

Note:

P&T Approval Date: 7/14/2015; P&T Revision Date: 4/26/2017, 5/18/2018, 6/19/2019; **Guideline Effective Date: 9/1/2019**

1 . Indications Drug Name: Afrezza (insulin human) Diabetes Mellitus Indicated to improve glycemic control in adult patients with diabetes mellitus.

2 . Criteria

Product Name: Afrezza*[a]

Page 24 Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Diagnosis of type 1 diabetes mellitus and used in combination with a basal insulin or continuous insulin pump

1.2 Diagnosis of type 2 diabetes mellitus

AND

2 - Patient is unable to self-inject medications (e.g. Humalog, Lantus, Levemir) due to one of the following:

• Physical impairment • Visual impairment • Lipohypertrophy • Documented needle-phobia to the degree that the patient has previously refused any injectable therapy or medical procedure (refer to DSM-5 for specific phobia diagnostic criteria [2])

AND

3 - FEV1 within the last 60 days is greater than or equal to 70% of expected normal as determined by the physician

AND

4 - Afrezza will NOT be approved in patients:

• Who smoke cigarettes • Who recently quit smoking (within the past 6 months)

Page 25 • With chronic lung disease (e.g. asthma, chronic obstructive pulmonary disease)

Product Name: Afrezza*[a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Repeat pulmonary function test confirms that patient has NOT experienced a decline of 20% or more in FEV1

AND

2 - Patient continues to be unable to self-inject short-acting insulin due to one of the following:

AND

3 - Patient continues to not smoke cigarettes Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y *Typically excluded from coverage

3 . Background

Page 26

Benefit/Coverage/Program Information

Background:

Coverage criteria outlined below are for patients unable to self-inject short-acting insulin.

4 . References

1. Afrezza [prescribing information]. Danbury, CT: MannKind Corporation; October 2018. 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013.

5 . Revision History

Date Notes

7/8/2020 Annual review. Updated references. Added state mandate language.

Page 27 Albuterol HFA, ProAir HFA, Proventil HFA - NonFormulary or Step Therapy

Prior Authorization Guideline

GL-59581 Albuterol HFA, ProAir HFA, Proventil HFA - NonFormulary or Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 1/1/2020 P&T Approval Date: 10/16/2019

P&T Revision Date:

1 . Criteria

Product Name: Albuterol HFA, ProAir HFA or Proventil HFA Approval Length 12 month(s) Guideline Type NonFormulary or Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to Ventolin HFA. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl

Page 28 y.

2 . Background

Benefit/Coverage/Program Information

Background:

This program requires a member to try and fail Ventolin HFA before providing coverage for albuterol HFA, ProAir® HFA, or Proventil HFA.

Albuterol HFA, ProAir® HFA and Proventil HFA are indicated for adults and children 4 years of age and older for the treatment of prevention of bronchospasm with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm. [1-2]

Additional Clinical Rules:

3 . References

1. Albuterol sulfate HFA [package insert]. Mason, OH: Prasco Laboratories; December 2015. 2. ProAir®HFA [package insert]. Waterford, Ireland: IVAX Pharmaceuticals Ireland; June 2016. 3. Proventil® HFA [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; December 2014.

4 . Revision History

Date Notes

12/31/2019 New program.

Page 29 Albuterol Tablets - PA/Med Nec

Prior Authorization Guideline

GL-73054 Albuterol Tablets - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 7/15/2020

P&T Revision Date:

1 . Indications Drug Name: Albuterol Tablets Obstructive Airway Disease Indicated for the relief of bronchchospasm in adults and children 6 years of age and older with reversible obstructive airway disease.

2 . Criteria

Product Name: Albuterol tablets [a] Diagnosis Obstructive Airway Disease Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 30

Approval Criteria

1 - Diagnosis of obstructive airway disease (e.g., Asthma)

AND

2 - Patient’s obstructive airway disease is being managed with both of the following:

2.1 One of the following controller medications:

• An inhaled corticosteroid (e.g., Arnuity Ellipta, Flovent Diskus, Flovent HFA, Pulmicort Flexhaler) • An inhaled corticosteroid/long-acting beta-agonist (e.g. Advair Diskus, Advair HFA, Breo Ellipa, Symbicort) • Spiriva HandiHaler/Respimat • A long-acting muscarinic antagonist/long-acting beta-agonist (e.g., Anoro Ellipta, Bevespi Aerosphere)

AND

2.2 History of failure, contraindication or intolerance to an inhaled short-acting beta-agonist (e.g. Ventolin HFA)

AND

3 - Prescriber attests that the benefits outweigh the risk Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albuterol tablets [a] Diagnosis Obstructive Airway Disease Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 31

Approval Criteria

1 - Documentation of positive clinical response to therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

Albuterol tablets are indicated for the relief of bronchchospasm in adults and children 6 years of age and older with reversible obstructive airway disease. Guidelines do not recommend the use of albuterol tablets and note they have a higher risk of side-effects. In addition guidelines note that there are no long-term safety studies that have been performed to assess the risk of severe exacerbations with albuterol tablets in patients not also taking an inhaled corticosteroid.

Additional Clinical Programs:

4 . References

1. Albuterol tablets [package insert]. Morgantown, WV: Mylan Pharmaceuticals, Inc.; July 2019. 2. Asthma Management and Prevention. Global Initiative for Asthma (GINA). 2020.

5 . Revision History

Date Notes

Page 32 9/8/2020 Updated effective date per PA team request. Guideline will be Proactiv e Review.

Page 33 Amitiza (lubiprostone) - PA/Med Nec

Prior Authorization Guideline

GL-89371 Amitiza (lubiprostone) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 2/18/2014 P&T Revision Date: 07/17/2019 ; 07/15/2020 ; 6/16/2021

1 . Indications Drug Name: Amitiza (lubiprostone) Chronic Idiopathic Constipation Indicated for the treatment of chronic idiopathic constipation.

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain Indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

Irritable Bowel Syndrome with Constipation Indicated for the treatment of irritable bowel syndrome with constipation in women aged 18 years and older.

2 . Criteria

Page 34 Product Name: Amitiza[a] Diagnosis Opioid-induced constipation in an adult with chronic, non-cancer pain Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following criteria:

1.1 Diagnosis of opioid-induced constipation in an adult with chronic, non-cancer pain

1.2 Diagnosis of opioid-induced constipation in patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation

AND

2 - History of failure, contraindication or intolerance to both of the following:

• OTC medication used for the treatment of constipation (document name and date tried) • Symproic (document date of trial)

Product Name: Amitiza[a] Diagnosis Opioid-induced constipation in an adult with chronic, non-cancer pain Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Page 35

1 - Documentation of positive clinical response to Amitiza therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Amitiza[a] Diagnosis Chronic idiopathic constipation Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of chronic idiopathic constipation

AND

2 - History of failure, contraindication or intolerance to one OTC medication used for the treatment of constipation (document name and date tried).

AND

3 - One of the following criteria:

3.1 History of failure, contraindication, or intolerance to Linzess

3.2 Age less than or equal to 17 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 36 Product Name: Amitiza[a] Diagnosis Chronic idiopathic constipation Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Product Name: Amitiza[a] Diagnosis Irritable bowel syndrome with constipation Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of irritable bowel syndrome with constipation

AND

2 - Patient was female at birth

AND

3 - History of failure, contraindication or intolerance to one OTC medication used for the treatment of constipation (document name and date tried).

AND

Page 37

4 - One of the following criteria:

4.1 History of failure, contraindication, or intolerance to Linzess

4.2 Age less than or equal to 17 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Amitiza[a] Diagnosis Irritable bowel syndrome with constipation Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Benefit/Coverage/Program Information

Background:

Amitiza (lubiprostone) is indicated for the treatment of chronic idiopathic constipation (CIC) in adults, the treatment of opioid-induced constipation (OIC) in adult patients with chronic non- cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation, and the treatment of irritable bowel

Page 38 syndrome with constipation (IBS-C) in women at least 18 years old. Linzess (linaclotide) is indicated in adults for the treatment of IBS-C and CIC. Linzess has a black box warning regarding the risk of serious dehydration in pediatric patients less than 17 years of age, and use of Linzess should be avoided in pediatric patients. Symproic (naldemedine) is indicated for OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Physicians and patients should periodically assess the need for continued treatment with Amitiza, Symproic or Linzess.

This prior authorization program is intended to encourage the use of lower cost alternatives. This program requires a member to try an over-the-counter medication (OTC) for constipation and either Linzess (linaclotide) for CIC or cIBS-C or Symproic for OIC before providing coverage for Amitiza (lubiprostone).

Additional Clinical Rules: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place. • Notification/Prior Authorization may be in place • Step Therapy may be in place

4 . References

1. Amitiza [package insert]. Lexington, MA: Takeda Pharmaceuticals, Inc.; November 2020. 2. Linzess [package insert]. Madison, NJ: Allergan; April 2021. 3. Symproic [package insert]. Raleigh, NC: BioDelivery Sciences International. May 2020.

5 . Revision History

Date Notes

7/2/2021 Annual review. Updated references.

Page 39 Amzeeq (minocycline 4% topical foam) - PA Med/Nec

Prior Authorization Guideline

GL-86639 Amzeeq (minocycline 4% topical foam) - PA Med/Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 4/15/2020 P&T Revision Date: 4/21/2021

1 . Indications Drug Name: Amzeeq (minocycline 4% topical foam) Acne Vulgaris Indicated for the topical treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and pediatric patients 9 years of age and older.

2 . Criteria

Product Name: Amzeeq [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 40

Approval Criteria

1 - Diagnosis of moderate to severe acne

AND

2 - History of failure, contraindication, or intolerance to an adequate trial of a topical antibiotic in combination with benzoyl peroxide [e.g., benzoyl peroxide/clindamycin (generic Duac), benzoyl peroxide/erythromycin (generic Benzamycin)]

AND

3 - Used in combination with another topical agent (e.g., benzoyl peroxide, retinoid) to minimize development of antibiotic resistance Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Amzeeq [a] Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Page 41 Benefit/Coverage/Program Information

Background: Amzeeq (minocycline 4% topical foam) is indicated for the topical treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and pediatric patients 9 years of age and older. Guidelines from the American Academy of Dermatology recommend topical antibiotics as a component of combination topical therapy for mild to moderate acne; systemic antibiotics are first-line in moderate to severe acne. Additional Clinical Rules:

• Supply limits may be in place.

4 . References

1. Amzeeq [package insert]. Bridgewater, NJ: VYNE Pharmaceuticals Inc.; January 2021. 2. Zaenglein, Andrea L. et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. May 2016;74(5):945–973.e33

5 . Revision History

Date Notes

5/7/2021 Annual review. Updated references.

Page 42 Angiotensin Receptor Blockers

Prior Authorization Guideline

GL-33136 Angiotensin Receptor Blockers

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 5/17/2005; P&T Revision Date: 1/25/2017. **Effective 7/1/2017**

1 . Indications Drug Name: Azor (amlodipine/olmesartan) Hypertension Indicated for the treatment of hypertension, alone or with other antihypertensive agents, and as initial therapy in patients likely to need multiple antihypertensive agents to achieve their blood pressure goals.

Drug Name: Edarbi (azilsartan) Hypertension Indicated for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction.

Drug Name: Edarbyclor (azilsartan/ chlorthalidone)

Page 43 Hypertension Indicated for the treatment of hypertension. Edarbyclor is also indicated for initial therapy of hypertension in patients who are likely to need multiple drugs to achieve their blood pressure goals.

Drug Name: Tekturna (aliskiren) Hypertension Indicated for the treatment of hypertension, to lower blood pressure.

Drug Name: Tekturna HCT (aliskiren and hydrochlorothiazide) Hypertension Indicated for the treatment of hypertension, to lower blood pressure. Tekturna HCT may be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.

Drug Name: Tribenzor (olmesartan/ amlodipine/ hydrochlorothiazide) Hypertension Indicated for the treatment of hypertension, to lower blood pressure. These fixed dose combinations are not indicated for the initial therapy of hypertension.

2 . Criteria

Product Name: Brand Azor, Edarbi, Edarbyclor, Tekturna, Tekturna HCT, Brand Tribenzor Guideline Type Step Therapy

Approval Criteria

1 - Trial and failure or intolerance to one of the following:

• benazepril • captopril • enalapril • fosinopril • lisinopril • moexipril • perindopril • quinapril • ramipril • benazepril-HCTZ • captopril-HCTZ • enalapril-HCTZ • fosinopril-HCTZ • lisinopril-HCTZ • moexipril-HCTZ

Page 44 • quinapril-HCTZ • amlodipine-benazepril • trandolapril-verapamil • losartan • losartan-HCTZ • candesartan • irbesartan • irbesartan-HCTZ • telmisartan • telmisartan-HCTZ • olmesartan • olmesartan-HCTZ

3 . References

1. Azor Prescribing Information. Daiichi Sankyo, May 2016. 2. Edarbi Prescribing Information. Takeda Pharmaceuticals. May 2014. 3. Edarbyclor Prescribing Information. Takeda Pharmaceuticals. October 2012. 4. Tekturna Prescribing Information. Noden Pharma USA, Inc. November 2016. 5. Tekturna HCT Prescribing Information. Noden Pharma USA, Inc. November 2016. 6. Tribenzor Prescribing Information. Daiichi Sankyo, May 2016.

Page 45 Anthelmintics - PA/Med Nec

Prior Authorization Guideline

GL-88669 Anthelmintics - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 11/18/2016 P&T Revision Date: 04/15/2020 ; 04/15/2020 ; 5/21/2021

1 . Indications Drug Name: Albenza (albendazole) Parenchymal neurocysticercosis Indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium.

Cystic hydatid disease Indicated for the treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus.

Drug Name: Emverm (mebendazole) Pinworm, whipworm, common roundworm, common hookworm, American hookworm Indicated for the treatment of Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (common roundworm), Ancylostoma duodenale (common hookworm), and Necator americanus (American hookworm) in single or mixed infections.

Page 46 2 . Criteria

Product Name: [Albenza, Emverm] [a] Diagnosis Enterobius vermicularis (pinworm) Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Enterobius vermicularis (pinworm)

AND

2 - History of failure, contraindication or intolerance to over-the-counter pyrantel pamoate Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albenza [a] Diagnosis Taenia solium (Neurocysticercosis) Approval Length 6 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Neurocysticercosis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Echinococcosis (Tapeworm) Approval Length 6 month(s)

Page 47 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Hydatid Disease [Echinococcosis (Tapeworm)] Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Ancylostoma/Necatoriasis (Hookworm) Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Ancylostoma/Necatoriasis (Hookworm) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Ascariasis (Roundworm) Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Ascariasis (Roundworm) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 48 Product Name: [Albenza, Emverm] [a] Diagnosis Toxocariasis (Roundworm) Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Toxocariasis (Roundworm) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Trichinellosis Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Trichinellosis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Trichuriasis (Whipworm) Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Trichuriasis (Whipworm) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage

Page 49 criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Capillariasis Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Capillariasis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Albenza, Emverm] [a] Diagnosis Baylisascaris Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Baylisascaris Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albenza [a] Diagnosis Clonorchiasis (Liver flukes) Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

Page 50

1 - Diagnosis of Clonorchiasis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albenza [a] Diagnosis Gnathostomiasis Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Gnathostomiasis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albenza [a] Diagnosis Strongyloidiasis Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Strongyloidiasis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albenza [a] Diagnosis Loiasis Approval Length 1 month(s)

Page 51 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Loiasis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Albenza [a] Diagnosis Opisthorchis Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Opisthorchis Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background: Albenza is indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium. Albenza is also indicated for the treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus.

Emverm is indicated for the treatment of Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (common roundworm), Ancylostoma duodenale (common hookworm) and Necator americanus (American hookworm) in single or mixed infections.

Page 52

CDC guidelines recommend use in several other parasitic infections. Additional Clinical Rules:

4 . References

1. CDC treatment guidelines. http://www.cdc.gov./parasites (accessed 4/1/2021). 2. Albenza [package insert]. Horsham, PA: Amedra Pharmaceuticals LLC; July2019. 3. Emverm [package insert]. Horsham, PA: Amedra Pharmaceuticals LLC; January 2019.

5 . Revision History

Date Notes

6/21/2021 Annual review. Removed Vermox from program due to product discont inuation. Updated references.

Page 53 Anti-Influenza Agents

Prior Authorization Guideline

GL-6427 Anti-Influenza Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 5/10/2005; CPS Revision Date: 4/9/2013

1 . Indications Drug Name: Relenza (zanamivir) Inhalation Powder [1, 2] Uncomplicated acute illness due to influenza A and B virus Relenza is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Relenza is indicated for prophylaxis of influenza in adults and pediatric patients 5 years of age and older.

Drug Name: Tamiflu (oseltamivir) [1, 2] Uncomplicated acute illness due to influenza A and B virus Tamiflu is indicated for the treatment of uncomplicated acute illness due to influenza infection in patients 2 weeks of age and older who have been symptomatic for no more than 2 days. Tamiflu is indicated for the

Page 54 prophylaxis of influenza in patients 1 year and older.

2 . Criteria

Product Name: Relenza Diagnosis Treatment Approval Length 5 Day Guideline Type Non Formulary

Approval Criteria

1 - For the treatment of influenza virus [1, 10]

AND

2 - Patient age greater than or equal to 7 years [1, 10] Notes NOTE TO PRESCRIBER: Relenza is not recommended for patients wit h underlying respiratory disease (eg, asthma, chronic obstructive pulm onary disease) or heart disease. [1, 10]

Product Name: Relenza Diagnosis Prophylaxis Approval Length 10 days for chemoprophylaxis in the household setting (quantity of 20 blisters per 180 days), or 28 days in the community setting (quantity of 56 blisters per 180 days) [1, B] Guideline Type Non Formulary

Approval Criteria

1 - For the prophylaxis of influenza virus [1, 10]

AND

Page 55

2 - Patient age greater than or equal to 5 years [1, 10] Notes NOTE TO PRESCRIBER: Relenza is not recommended for patients wit h underlying respiratory disease (eg, asthma, chronic obstructive pulm onary disease) or heart disease. [1, 10]

Product Name: Tamiflu Diagnosis Treatment Approval Length 5 Day Guideline Type Non Formulary

Approval Criteria

1 - For the treatment of influenza virus [2, 10]

AND

2 - Patient age greater than or equal to 2 weeks [2, 10]

Product Name: Tamiflu Diagnosis Prophylaxis Approval Length 10 days (30 mg: 20 capsules per 180 days, 45 and 75 mg: 10 capsules per 180 days, 6 mg/mL oral suspension: 180 mL per month) [C]; authorization may be issued for up to 6 weeks of therapy (for a total quantity of 42 capsules) for residents of nursing homes or long-term care facilities or during a community outbreak [D] Guideline Type Non Formulary

Approval Criteria

1 - For the prophylaxis of influenza virus [2, 10]

AND

2 - Patient age greater than or equal to 1 year [2, 10]

Page 56 Product Name: Relenza Diagnosis Treatment Approval Length 5 days (additional quantity of 20 blisters) Guideline Type Quantity Limit

Approval Criteria

1 - For the treatment of influenza virus [1, 10]

AND

2 - Patient age greater than or equal to 7 years [1, 10]

AND

3 - One of the following:

3.1 Dose per day (mg/day) is supported in the dosage and administration section of the manufacturer's prescribing information

3.2 Dose per day (mg/day) is supported by one of following compendia:

• American Hospital Formulary Service Drug Information • Micromedex DRUGDEX System

Notes NOTE TO PRESCRIBER: Relenza is not recommended for patients wit h underlying respiratory disease (eg, asthma, chronic obstructive pulm onary disease) or heart disease. [1, 10]

Product Name: Relenza Diagnosis Prophylaxis Guideline Type Quantity Limit

Page 57 Approval Criteria

1 - In persons who are at high priority for chemoprophylaxis defined by one of the following: [10, 11]

1.1 Both of the following:

1.1.1 One of the following:

1.1.1.1 High-risk persons [A] during the 2 weeks after vaccination before an adequate immune response to the influenza vaccine develops

1.1.1.2 All of the following:

• High-risk children during the 6 weeks after vaccination before an adequate immune response to the influenza vaccine develops • Child was not previously vaccinated • Child requires 2 doses of vaccine

AND

1.1.2 Influenza viruses are circulating in the community

1.2 Both of the following:

1.2.1 Adults and children who are at high risk [A]

AND

1.2.2 One of the following:

1.2.2.1 Influenza vaccination is contraindicated

Page 58 1.2.2.2 Influenza vaccination is unavailable (eg, due to shortage)

1.2.2.3 Influenza vaccination is expected to have low effectiveness (eg, persons who are significantly immunocompromised)

1.2.2.4 Situations in which there is documented low influenza vaccine clinical effectiveness due to circulation of influenza virus strains that are antigenically distant from the vaccine strains (ie, substantial increase in vaccine failure is anticipated) as determined by federal, state, and local public health institutions

1.2.2.5 Both of the following:

• Patient has not yet received influenza vaccine • Influenza activity has already been detected in the community

1.3 Unvaccinated persons who are in close contact with persons at high risk [A] during periods of influenza activity

1.4 Both of the following:

• All residents in institutions (eg, nursing homes, long-term care facilities) • Institution is experiencing influenza outbreaks

AND

2 - Patient age greater than or equal to 5 years [1, 10]

Page 59

AND

3 - One of the following:

3.1 Dose per day (mg/day) is supported in the dosage and administration section of the manufacturer's prescribing information

3.2 Dose per day (mg/day) is supported by one of following compendia:

• American Hospital Formulary Service Drug Information • Micromedex DRUGDEX System

Notes NOTE TO PRESCRIBER: Relenza is not recommended for patients wit h underlying respiratory disease (eg, asthma, chronic obstructive pulm onary disease) or heart disease. [1, 10]

Product Name: Tamiflu Diagnosis Treatment Approval Length 5 days (additional quantities of: 20 capsules for 30 mg; 10 capsules for 45 mg, 75 mg; 180 mL for 6 mg/mL oral suspension) Guideline Type Quantity Limit

Approval Criteria

1 - For the treatment of influenza virus [2, 10]

AND

2 - Patient age greater than or equal to 2 weeks [2, 10]

AND

3 - One of the following:

Page 60

3.1 Dose per day (mg/day) is supported in the dosage and administration section of the manufacturer's prescribing information

3.2 Dose per day (mg/day) is supported by one of following compendia:

• American Hospital Formulary Service Drug Information • Micromedex DRUGDEX System

Product Name: Tamiflu Diagnosis Prophylaxis Guideline Type Quantity Limit

Approval Criteria

1 - In persons who are at high priority for chemoprophylaxis defined by one of the following: [10, 11]

1.1 Both of the following:

1.1.1 One of the following:

1.1.1.1 High-risk persons [A] during the 2 weeks after vaccination before an adequate immune response to the influenza vaccine develops

1.1.1.2 All of the following:

AND

Page 61 1.1.2 Influenza viruses are circulating in the community

1.2 Both of the following:

1.2.1 Adults and children who are at high risk [A]

AND

1.2.2 One of the following:

1.2.2.1 Influenza vaccination is contraindicated

1.2.2.2 Influenza vaccination is unavailable (eg, due to shortage)

1.2.2.3 Influenza vaccination is expected to have low effectiveness (eg, persons who are significantly immunocompromised)

1.2.2.5 Both of the following:

• Patient has not yet received influenza vaccine • Influenza activity has already been detected in the community

Page 62

1.3 Unvaccinated persons who are in close contact with persons at high risk [A] during periods of influenza activity

1.4 Both of the following:

• All residents in institutions (eg, nursing homes, long-term care facilities) • Institution is experiencing influenza outbreaks

AND

2 - Patient age greater than or equal to 1 year [2, 10]

AND

3 - One of the following:

3.1 Dose per day (mg/day) is supported in the dosage and administration section of the manufacturer's prescribing information

3.2 Dose per day (mg/day) is supported by one of following compendia:

• American Hospital Formulary Service Drug Information • Micromedex DRUGDEX System

3 . Background

Clinical Practice Guidelines

Page 63 Centers for Disease Control and Prevention (2012-2013) [10]

Influenza antiviral prescription drugs can be used to treat influenza or to prevent influenza. The two FDA-approved influenza antiviral medications are recommended for use in the United States during the 2012-2013 influenza season: oseltamivir (Tamiflu) and zanamivir (Relenza). Oseltamivir and zanamivir are chemically related antiviral medications known as neuraminidase inhibitors that have activity against both influenza A and B viruses.

Treatment

Clinical trials and observational data show that early antiviral treatment can shorten the duration of fever and illness symptoms, and reduce the risk of complications from influenza (e.g., otitis media in young children, pneumonia, respiratory failure, and death) and shorten the duration of hospitalization. Clinical benefit is greatest when antiviral treatment is administered early, especially within 48 hours of influenza illness onset. Antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who is hospitalized, has severe, complicated, or progressive illness, or is at higher risk for influenza complications.

Persons at higher risk for influenza complications recommended for antiviral treatment include:

· Children aged < 2 years

· Adults aged greater than or equal to 65 years

· Persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability [mental retardation], moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)

· Persons with immunosuppression, including that caused by medications or by HIV infection

· Women who are pregnant or postpartum (within 2 weeks after delivery)

· Persons aged <19 years who are receiving long-term aspirin therapy

Page 64 · American Indians/Alaska Natives

· Persons who are morbidly obese (i.e., body-mass index greater than or equal to 40)

· Residents of nursing homes and other chronic-care facilities

Clinical judgment, on the basis of the patient’s disease severity and progression, age, underlying medical conditions, likelihood of influenza, and time since onset of symptoms, is important when making antiviral treatment decisions for high-risk outpatients. When indicated, antiviral treatment should be started as soon as possible after illness onset, ideally within 48 hours of symptom onset. However, antiviral treatment might still be beneficial in patients with severe, complicated or progressive illness and in hospitalized patients when started after 48 hours of illness onset as indicated by observational studies. Treatment should not wait for laboratory confirmation of influenza.

Chemoprophylaxis

Annual influenza vaccination is the best way to prevent influenza because vaccination can be given well before influenza virus exposures occur, and can provide safe and effective immunity throughout the influenza season. Antiviral medications are 70% to 90% effective in preventing influenza and are useful adjuncts to vaccination.

CDC does not recommend widespread or routine use of antiviral medications for chemoprophylaxis so as to limit the possibilities that antiviral resistant viruses could emerge. Indiscriminate use of chemoprophylaxis might promote resistance to antiviral medications, or reduce antiviral medication availability for treatment of persons at higher risk for influenza complications or those who are severely ill. An emphasis on close monitoring and early initiation of antiviral treatment is an alternative to chemoprophylaxis after a suspected exposure for some persons.

To be effective as chemoprophylaxis, an antiviral medication must be taken each day for the duration of potential exposure to a person with influenza and continued for 7 days after the last known exposure. For persons taking antiviral chemoprophylaxis after inactivated influenza vaccination, the recommended duration is until immunity after vaccination develops (antibody development after vaccination takes about two weeks in adults and can take longer in children depending on age and vaccination history). Antiviral chemoprophylaxis generally is not recommended if more than 48 hours have elapsed since the last exposure to an infectious person. Patients receiving antiviral chemoprophylaxis should be encouraged to seek medical evaluation as soon as they develop a febrile respiratory illness that might indicate influenza.

Chemoprophylactic use of antiviral medications to control outbreaks among

Page 65 high risk persons in institutional settings is recommended. For example, when influenza is identified as a cause of respiratory outbreak among nursing home residents, use of antiviral chemoprophylaxis for all exposed or at-risk residents and for unvaccinated health care personnel is recommended. For vaccinated staff, antiviral chemoprophylaxis can be administered up to 2 weeks following influenza vaccination. For more information on the control of institutional outbreaks, please see the IDSA guidelines.

The following are examples of how antiviral medications can be considered for chemoprophylaxis to prevent influenza:

· Prevention of influenza in persons at high risk of influenza complications during the first two weeks following vaccination after exposure to an infectious person.

· Prevention for people with severe immune deficiencies or others who might not respond to influenza vaccination, such as persons receiving immunosuppressive medications, after exposure to an infectious person.

· Prevention for people at high risk for complications from influenza who cannot receive influenza vaccine due to a contraindication after exposure to an infectious person.

· Prevention of influenza among residents of institutions, such as long- term care facilities, during influenza outbreaks in the institution.

Infectious Diseases Society of America 2009 [11]

Treatment

Neuraminidase inhibitors (oseltamivir and zanamivir) have activity against both influenza A and B viruses. Both zanamivir and the adamantanes are active against oseltamivir-resistant A influenza (H1N1) viruses. Rimantadine is preferred over amantadine because of its more favorable adverse effect profile. Ongoing surveillance for antiviral resistance is occurring in laboratories worldwide. Clinicians who treat patients with influenza should be aware of local public health data, when available, on the type and subtypes of influenza circulating in their area.

Chemoprophylaxis

Influenza vaccination is the primary tool to prevent influenza and antiviral chemoprophylaxis is not a substitute for influenza vaccination. When influenza viruses are circulating in the community, chemoprophylaxis can be considered for:

Page 66 · High-risk persons during the 2 weeks after vaccination before an adequate immune response to inactivated vaccine develops (6 weeks for children who were not previously vaccinated and who require 2 doses of vaccine).

· Adults and children aged greater than or equal to 1 year who are at high risk of developing complications from influenza for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness (e.g., persons who are significantly immunocompromised). Contraindications to vaccination include anaphylactic hypersensitivity to eggs or other vaccine components, moderate-to-severe febrile illness, and as a precaution, a history of Guillain-Barre´ syndrome within 6 weeks after receipt of a prior influenza vaccination.

· Adults and children aged greater than or equal to 1 year who are at high risk of developing complications from influenza virus infection and have not yet received influenza vaccine when influenza activity has already been detected in the community. Whenever possible, influenza vaccine should be administered, and vaccination should continue for recommended persons until influenza is no longer in community circulation.

· Unvaccinated adults, including health care workers, and for children aged greater than or equal to 1 year who are in close contact with persons at high risk of developing influenza complications during periods of influenza activity. Whenever possible, influenza vaccine should be administered; 2 weeks after administration, chemoprophylaxis may be discontinued (6 weeks for children who were not previously vaccinated and who require 2 doses of vaccine).

· All residents (vaccinated and unvaccinated) in institutions, such as nursing homes and long-term care facilities, that are experiencing influenza outbreaks.

· Persons at the highest risk of influenza-associated complications. The risk of influenza associated complications is not identical among all high- risk persons, and antiviral chemoprophylaxis is likely to have the greatest benefit among those at highest risk of influenza complications and death, such as recipients of hematopoietic stem cell transplants.

· Persons at high-risk of developing complications from influenza if influenza vaccine is not available due to shortage. If vaccine is available, it should be administered to these persons.

· High-risk persons in situations in which there is documented low influenza vaccine clinical effectiveness because of the circulation of

Page 67 influenza virus strains that are antigenically distant from the vaccine strains, such that a substantial increase in vaccine failures is anticipated, as determined by federal, state, and local public health authorities.

4 . Endnotes

A. Persons at high risk of complications from influenza who should be considered for antiviral therapy: [10, 11] (1) Unvaccinated infants aged 12-24 months (2) Persons with asthma or other chronic pulmonary diseases, such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults (3) Persons with hemodynamically significant cardiac disease (4) Persons who have immunosuppressive disorders or who are receiving immunosuppressive therapy (5) HIV-infected persons (6) Persons with sickle cell anemia and other hemoglobinopathies (7) Persons with diseases that require long-term aspirin therapy, such as rheumatoid arthritis or Kawasaki disease (8) Persons with chronic renal dysfunction (9) Persons with cancer (10)Persons with chronic metabolic disease, such as diabetes mellitus (11)Persons with neuromuscular disorders, seizure disorders, or cognitive dysfunction that may compromise the handling of respiratory secretions (12)Adults aged > 65 years (13)Residents of any age of nursing homes or other long-term care institutions B. The safety and effectiveness of prophylaxis with Relenza have not been established for longer than 28 days duration. [1] C. Tamiflu has been studied for the prophylaxis of influenza in close contacts. These studies have demonstrated the protective efficacy of Tamiflu and included prophylactic regimens that lasted 7 to 10 days. [2, 4, 8] D. The prophylaxis studies conducted in healthy unvaccinated adults during a community outbreak and in elderly residents of skilled nursing homes (as described in the Tamiflu prescribing information) lasted for 42 days (6 weeks). [2]

5 . References

1. Relenza Prescribing Information. GlaxoSmithKline. December 2011. 2. Tamiflu Prescribing Information. Roche Labortatories Inc. December 2012. 3. Monto AS, Webster A, Keene O. Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis. J Antimicrob hemother. 1999 Nov;44 Suppl B:23-9. 4. Welliver R, Monto AS, Carewicz O, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001 Feb 14;285(6):748-54. 5. Treanor JJ, Hayden FG, Vrooman PS. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 2000 Feb 23;283(8):1016-24. 6. Centers for Disease Control and Prevention. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR, July 29, 2005, Vol. 54(RR-8):1-44.

Page 68 7. Centers for Disease Control and Prevention. Prevention and Control of Influenza Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR 2008;57(RR07):1-60. 8. Hayden FG, Belshe R, Villanueva C, et al. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis. 2004 Feb 1;189:440-9. 9. Center for Disease Control and Prevention. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for 2009 – 2010 season. http://www.cdc.gov/H1N1flu/recommendations.htm. Updated September 22, 2009. Accessed October 8, 2009. 10. Centers for Disease Control and Prevention. 2012-2013 Influenza antiviral medications: A summary for clinicians. http://www.cdc.gov/flu/professionals/antivirals/summary- clinicians.htm. Updated December 22, 2012. Accessed February 28, 2013. 11. Harper SA, Bradley, JS, Englund JA, et al. Seasonal influenza in adults and children - diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clinical Infectious Diseases 2009;48:1003-32.

Page 69 Anticonvulsants - Banzel (rufinamide), Diacomit (stiripentol), Nayzilam (midazolam), Sabril (vigabatrin), Sympazan (clobazam), Valtoco (diazepam)

Prior Authorization Guideline

GL-90141 Anticonvulsants - Banzel (rufinamide), Diacomit (stiripentol), Nayzilam (midazolam), Sabril (vigabatrin), Sympazan (clobazam), Valtoco (diazepam)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 7/18/2018 P&T Revision Date: 05/17/2019 ; 03/18/2020 ; 07/15/2020 ; 12/16/2020 ; 5/21/2021

1 . Indications Drug Name: Banzel (rufinamide) and Sympazan (clobazam)* Seizures associated with Lennox-Gastaut syndrome (LGS) Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS).

Drug Name: Diacomit (stiripentol) Seizures associated with Dravet syndrome Indicated for seizures associated with Dravet syndrome in patients taking clobazam.

Drug Name: Sabril (vigabatrin) Refractory complex partial seizures Indicated as adjunctive therapy for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for infantile spasms for whom the potential benefits outweigh the risk of vision loss.

Page 70 Drug Name: Nayzilam (midazolam) and Valtoco (diazepam) Acute treatment of intermittent, stereotypic episodes of frequent seizure activity Indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern

2 . Criteria

Product Name: Banzel Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 All of the following:

• Diagnosis of seizures associated with Lennox-Gastaut syndrome (LGS) • Used as adjunctive therapy (defined as accessory treatment used in combination to enhance primary treatment) • Not used as primary treatment

1.2 For continuation of prior therapy for a seizure disorder

Product Name: Sympazan* Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

Page 71

1 - One of the following:

1.1 All of the following:

1.1.1 One of the following:

• Diagnosis of seizures associated with Lennox-Gastaut syndrome (LGS) • Diagnosis of refractory partial onset seizures (four or more uncontrolled seizures per month after an adequate trial of at least two antiepileptic drugs) • Diagnosis of Dravet syndrome

AND

1.1.2 Both of the following:

• Used as adjunctive therapy (defined as accessory treatment used in combination to enhance primary treatment) • Not used as primary treatment

1.2 For continuation of prior therapy for a seizure disorder

Product Name: Sabril Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 All of the following:

• Diagnosis of partial-onset seizures • Used as adjunctive therapy (defined as accessory treatment used in combination to enhance primary treatment) • Not used as primary treatment • Patient has had inadequate response to several (at least three) alternative

Page 72 anticonvulsants

1.2 Diagnosis of infantile spasms

1.3 For continuation of prior therapy for a seizure disorder

Product Name: Diacomit Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Diagnosis of Dravet syndrome and currently taking clobazam

1.2 For continuation of prior therapy for a seizure disorder

Product Name: Nayzilam Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of seizure clusters or acute repetitive seizures that are distinct from the patient’s usual seizure pattern

Page 73

Product Name: Valtoco Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of seizure clusters or acute repetitive seizures that are distinct from the patient’s usual seizure pattern

AND

2 - ONE of the following criteria:

2.1 Patient is less than 12 years of age

2.2 History of failure, contraindication, or intolerance to Nayzilam

Product Name: Banzel, Diacomit, Nayzilam, Sabril, or Sympazan*, Valtoco Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to therapy

3 . Background

Benefit/Coverage/Program Information

Page 74 Background:

Banzel (rufinamide), and Sympazan (clobazam)* are indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS). There is some clinical evidence to support the use of clobazam for refractory partial onset seizures.

Diacomit (stiripentol) is indicated for seizures associated with Dravet syndrome in patients taking clobazam.

Sabril (vigabatrin) is indicated as adjunctive therapy for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for infantile spasms for whom the potential benefits outweigh the risk of vision loss.

Adjunctive therapy is defined as treatment administered in addition to another therapy. Coverage will not be provided for Banzel as primary treatment.

Nayzilam (midazolam) and Valtoco (diazepam) are indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern.

Additional Clinical Programs:

• *Typically excluded from coverage. • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Banzel [package insert]. Woodcliff Lake, NJ: Eisai, Inc. November 2019. 2. Glossary of Terms. Epilepsy Foundation Web site. http://www.epilepsy.co/gethelp/toolbox/glossaryAccessed August 30, 2016. 3. Sabril [package insert]. Lundbeck, Deerfield, IL: February 2020. 4. Sympazan [package insert]. Warren, NJ: Aquestive Therapeutics. November 2018. 5. Diacomit [package insert]. Redwood City, CA: Biocodex Inc. August 2018. 6. Koeppen, D. et al. Clobazam in therapy-resistant patients with partial epilepsy: A double- blind placebo-controlled crossover study. Epilepsia 28(5);495-506. October 1987. 7. Micahel, B. Clobazam as an add-on in the management of refractory epilepsy. Cochrane Database of Systemic Reviews 2008. 8. Nayzilam [package insert]. Smyrna, GA: UCB, Inc. May 2019. 9. Valtoco [package insert]. San Diego, CA: Neurelis, Inc. January 2020.

Page 75 5 . Revision History

Date Notes

7/21/2021 5/2021 P&T - Removed Fintepla from criteria.

Page 76 Anticonvulsants - Single Source Brand - PA/Med Nec

Prior Authorization Guideline

GL-76715 Anticonvulsants - Single Source Brand - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 2/18/2014 P&T Revision Date: 11/15/2019 ; 07/15/2020 ; 07/15/2020 ; 07/15/2020 ; 10/21/2020

1 . Criteria

Product Name: [Aptiom, Briviact, Fycompa, Vimpat, or Xcopri] [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 All of the following:

1.1.1 One of the following:

Page 77 • For Aptiom, Briviact, Vimpat or Xcopri: diagnosis of partial-onset seizures • For Fycompa: diagnosis of partial-onset or primary generalized tonic-clonic seizures

AND

1.1.2 History of greater than or equal to 8 week trial [b] of at least two of the following (any release formulation qualifies):

• Carbamazepine (e.g., generic Tegretol) • Divalproex (e.g., generic Depakote) • Gabapentin (e.g., generic Neurontin) • Lamotrigine (e.g., generic Lamictal) • Levetiracetam (e.g., generic Keppra) • Oxcarbazepine (e.g., generic Trileptal) • Phenytoin (e.g., generic Dilantin) • Pregabalin (e.g., generic Lyrica) • Topiramate (e.g., generic Topamax) • Valproic acid (e.g., generic Depakene) • Zonisamide (generic Zonegran)

AND

1.1.3 One of the following:

1.1.3.1 Both of the following:

• Documented history of persisting seizures after titration to the highest tolerated dose with each medication trial • Lack of compliance as a reason for treatment failure has been ruled out

1.1.3.2 Both of the following:

• Documentation of failure due to intolerable side effects • Reasonable efforts were made to minimize the side effect (e.g., change timing of dosing, divide dose out for more frequent but smaller doses, etc.)

Page 78 1.2 For continuation of prior therapy for a seizure disorder Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Connecticut and Kentucky business, only a 30 day trial will be req uired.

Product Name: Epidiolex [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of seizures associated with Dravet syndrome or tuberous sclerosis complex

2 - All of the following :

2.1 Diagnosis of seizures associated with Lennox-Gastaut syndrome

AND

2.2 History of greater than or equal to 8 week trial [b], contraindication or intolerance of at least two of the following (any release formulation qualifies):

• Divalproex (e.g., generic Depakote) • Lamotrigine (e.g., generic Lamictal) • Topiramate (e.g., generic Topamax) • Valproic acid (e.g., generic Depakene)

AND

2.3 One of the following:

2.3.1 Both of the following:

• Documented history of persisting seizures after titration to the highest tolerated dose with each medication trial

Page 79 • Lack of compliance as a reason for treatment failure has been ruled out

2.3.2 Both of the following:

• Documentation of failure due to intolerable side effects. • Reasonable efforts were made to minimize the side effect (e.g., change timing of dosing, divide dose out for more frequent but smaller doses, etc.)

3 - For continuation of prior therapy for a seizure disorder Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Connecticut and Kentucky business, only a 30 day trial will be req uired.

Product Name: Fintepla [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - All of the following:

1.1 Diagnosis of seizures associated with Dravet syndrome

AND

1.2 History of greater than or equal to 8 week trial [b] of at least two of the following (any release formulation qualifies):

• Divalproex (e.g., generic Depakote) • Levetiracetam (e.g., generic Keppra) • Topiramate (e.g., generic Topamax) • Valproic acid (e.g., generic Depakene)

Page 80 • Zonisamide (generic Zonegran)

AND

1.3 One of the following:

1.3.1 Both of the following:

• Documented history of persisting seizures after titration to the highest tolerated dose with each medication trial • Lack of compliance as a reason for treatment failure has been ruled out

1.3.2 Both of the following:

• Documentation of failure due to intolerable side effects. • Reasonable efforts were made to minimize the side effect (e.g. change timing of dosing, divide dose out for more frequent but smaller doses, etc.)

2 - For continuation of prior therapy for a seizure disorder Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Connecticut and Kentucky business, only a 30 day trial will be req uired.

2 . Background

Benefit/Coverage/Program Information

Background: This program requires a member to try at least two antiepileptic medications prior to receiving coverage for Aptiom, Briviact, Fintepla, Fycompa, Vimpat, Xcopri, or for Epidiolex when it is used for seizures associated with Lennox-Gastaut syndrome. Epidiolex for seizures associated with Dravet syndrome or tuberous sclerosis complex do not require a trial of

Page 81 alternative antiepileptic medications. Additional Clinical Programs:

3 . References

1. Anon; Drugs for Epilespy, Treatment Guidelines from The Medical Letter, 2013; 11:9-19. 2. Britton JW. Antiepileptic drug withdrawal: literature review. Mayo Clin Proc. 2002;77(12):1378. 3. Fycompa prescribing information. Eisia Inc., Woodcliff, NJ. April May 2019. 4. Kwan P, et al. Definition of drug resistant epilepsy; consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010; 51(6);1069. 5. Perucca E, et al. The pharmacological treatment of epilepsy in adults. Lancet Neurol 2011; 10:446-56. 6. Vimpat prescribing information. UCB, Inc. Smyrna, GA. June 2019. 7. Aptiom prescribing information. Sunovion Pharmaceuticals Inc. Marlborough, MA. March 2019. 8. Briviact prescribing information. UCB, Inc. Smyrna, GA. May 2019. 9. Epidiolex [package insert]. Carlsbad, CA: Greenwich Biosciences, Inc; August 2020. 10. Xcopri [package insert]. Paramus, NJ: SK Life Science, Inc; March 2020. 11. Fintepla [package insert]. Emeryville, CA: Zogenix, Inc; June 2020.

4 . Revision History

Date Notes

11/10/2020 Addition of Fintepla to program. Updated Epidiolex criteria to include s eizures associated with tuberous sclerosis complex.

Page 82 Anticonvulsants - Step Therapy

Prior Authorization Guideline

GL-76592 Anticonvulsants - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 2/15/2019 P&T Revision Date: 09/18/2019 ; 03/18/2020 ; 03/18/2020 ; 10/21/2020

1 . Criteria

Product Name: Oxtellar XR Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - One of the following criteria:

1.1 Both of the following:

1.1.1 History of greater than or equal to a 2 week trial of generic oxcarbazepine

Page 83

AND

1.1.2 History of an inadequate response to generic oxcarbazepine

1.2 History of intolerance to generic oxcarbazepine

1.3 Patient is receiving Oxtellar XR for the treatment of a seizure disorder

Product Name: Qudexy XR (brand and authorized generic), Trokendi XR Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - One of the following criteria:

1.1 Both of the following:

1.1.1 History of greater than or equal to a 2 week trial of one generic topiramate immediate- release (IR) product

AND

1.1.2 History of an inadequate response to one generic topiramate immediate-release (IR) product

1.2 History of intolerance to one generic topiramate immediate-release (IR) product

Page 84

1.3 Patient is receiving Trokendi XR or Qudexy XR (brand and authorized generic) for the treatment of a seizure disorder

2 . Background

Benefit/Coverage/Program Information

Background:

Step Therapy programs are utilized to encourage use of lower cost alternatives for certain therapeutic classes.

This program requires a member to try one generic topiramate immediate-release product prior to coverage of Qudexy XR (brand and authorized generic) or Trokendi XR, and generic oxcarbazepine prior to coverage of Oxtellar XR. There will be exceptions for members with a documented diagnosis of a seizure disorder.

Additional Clinical Rules:

Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

3 . References

1. Oxtellar XR [package insert]. Rockville, MD: Supernus Pharmceuticals Inc; December 2018. 2. Qudexy XR [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, Inc; February 2020. 3. Trokendi XR [package insert]. Rockville, MD: Supernus Pharmaceutical Inc; February 2019.

4 . Revision History

Page 85 Date Notes

11/4/2020 Annual review. Updated references.

Page 86 Antidepressants - Step Therapy

Prior Authorization Guideline

GL-89790 Antidepressants - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 11/19/2014 P&T Revision Date: 05/17/2019 ; 05/15/2020 ; 6/16/2021

1 . Criteria

Product Name: Trintellix[a], Fetzima [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - One of the following:

1.1 History of failure after at least 4 weeks of therapy, contraindication, or intolerance to at least THREE of any formulation of the following (document drug and date of trials):

Page 87 • bupropion • citalopram • duloxetine • escitalopram • fluoxetine • fluvoxamine • paroxetine • sertraline • venlafaxine IR/ER (capsules)

1.2 The requested medication was initiated during a recent inpatient mental health hospitalization, and the member is stabilized on the requested medication

1.3 Member is new to the plan and currently stabilized on the requested medication (as evidenced by coverage effective date of less than or equal to 120 days) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

2 . Background

Benefit/Coverage/Program Information

Background: Step therapy type programs have been utilized to encourage use of lower cost alternatives for certain therapeutic classes. This program requires a trial of at least three step one medications before providing coverage for Trintellix or Fetzima. If a member has three step one medications in claim’s history in the previous 180 days then Trintellix or Fetzima will automatically process. Members with a history of Trintellix or Fetzima as documented in claims history will be allowed continued coverage of their current therapy. Members new to therapy will be required to meet the below criteria. Other Clinical Programs: Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and re-authorization

Page 88 based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. Supply limits may also be in place.

3 . References

1. Fetzima [Package Insert]. St. Louis, MO: Forest Pharmaceuticals, Inc.; October 2019. 2. Trintellix [Package Insert]. Deerfield, IL: Takeda Pharmaceuticals, America; January 2021. 3. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder, third edition. Oct. 2010. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf

4 . Revision History

Date Notes

7/12/2021 Added documentation of first line drug tried. Updated references.

Page 89 Antiemetics Quantity Limit Overrides

Prior Authorization Guideline

GL-87091 Antiemetics Quantity Limit Overrides

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 2/25/2016 P&T Revision Date: 05/14/2020 ; 08/13/2020

1 . Indications Drug Name: Akynzeo (netupitant/palonosetron) Chemotherapy-induced nausea and vomiting Indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Akynzeo is an oral fixed combination of palonosetron and netupitant: palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

Drug Name: Anzemet (dolasetron) Chemotherapy-induced nausea and vomiting Indicated for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses in adults and children 2 years and older.

Off Label Uses: Radiotherapy-induced nausea and vomiting Used for the prevention and treatment of nausea and vomiting induced by radiation therapy. [11, 12]

Postoperative nausea and vomiting Used orally for the prevention of postoperative nausea

Page 90 and vomiting. [13]

Drug Name: Cesamet (nabilone) Chemotherapy Induced Nausea and Vomiting Indicated for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of any group of patients treated with Cesamet can be expected to experience disturbing psychotomimetic reactions not observed with other antiemetic agents. Because of its potential to alter the mental state, Cesamet is intended for use under circumstances that permit close supervision of the patient by a responsible individual particularly during initial use of Cesamet and during dose adjustments. Cesamet contains nabilone, which is controlled in Schedule II of the Controlled Substances Act. Schedule II substances have a high potential for abuse. Prescriptions for Cesamet should be limited to the amount necessary for a single cycle of chemotherapy (i.e., a few days). Cesamet capsules are not intended to be used on as needed basis or as a first antiemetic product prescribed for a patient. As with all controlled drugs, prescribers should monitor patients receiving nabilone for signs of excessive use, abuse and misuse. Patients who may be at increased risk for substance abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse) or mental illness.

Drug Name: Emend (aprepitant) Chemotherapy-induced nausea and vomiting Indicated, in combination with other antiemetic agents, in patients 6 months of age and older for oral suspension, or 12 years of age and older for the capsules, for the prevention of: (1) acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; (2) nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Limitations of Use: (1) Emend has not been studied for the treatment of established nausea and vomiting; (2) Chronic continuous administration of Emend is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use.

Postoperative Nausea and Vomiting - capsules only Indicated in adults for the prevention of postoperative nausea and vomiting. Limitations of Use: (1) Emend has not been studied for the treatment of established nausea and vomiting; (2) Chronic continuous administration of Emend is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use.

Drug Name: Granisetron Chemotherapy-induced nausea vomiting Indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin.

Radiation-induced nausea and vomiting Indicated for the prevention of nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation.

Off Label Uses: Postoperative nausea and vomiting Used for the prevention of

Page 91 postoperative nausea and vomiting. [14, 15]

Drug Name: Marinol (dronabinol) Chemotherapy-induced nausea and vomiting Indicated in adults for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.

Anorexia in patients with AIDS Indicated in adults for the treatment of anorexia associated with weight loss in patients with AIDS.

Drug Name: Sancuso (granisetron transdermal system) Chemotherapy-induced nausea and vomiting Indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days duration.

Drug Name: Sustol (granisetron injection) Chemotherapy-induced nausea and vomiting Indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

Drug Name: Varubi (rolapitant) Chemotherapy-induced nausea and vomiting Indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

Drug Name: Zofran (ondansetron), Zuplenz (ondansetron oral soluble film) Chemotherapy-induced nausea and vomiting Indicated for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2. Also indicated for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

Radiotherapy-induced nausea and vomiting Indicated for the prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.

Postoperative nausea and vomiting Indicated for the prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, Zofran Tablets, Zofran ODT Orally Disintegrating Tablets, Zofran Oral Solution, and Zuplenz are recommended even where the incidence of postoperative nausea and/or vomiting is low.

Page 92 Off Label Uses: Hyperemesis gravidarum Used in the management of hyperemesis gravidarum. [10, 16]

2 . Criteria

Product Name: Akynzeo, Anzemet, Cesamet, Generic dronabinol, Brand Emend, Generic aprepitant, granisetron, Brand Marinol, Generic ondansetron 24 mg tablet, Generic ondansetron oral solution, Generic ondansetron ODT, Sancuso, Sustol, Varubi, Brand Zofran oral solution, or Zuplenz Diagnosis Chemotherapy-induced nausea and vomiting Approval Length 12 month(s) Guideline Type Quantity Limit

Approval Criteria

1 - Diagnosis of chemotherapy-induced nausea and vomiting

AND

2 - Patient is receiving moderately to highly emetogenic chemotherapy

AND

3 - Provider attests that a higher quantity is needed due to the number of chemotherapy sessions

Product Name: Anzemet, granisetron, Generic ondansetron 24 mg tablet, Generic ondansetron oral solution, Generic ondansetron ODT, Brand Zofran oral solution, or Zuplenz Diagnosis Radiotherapy-induced nausea and vomiting Approval Length 12 month(s) Guideline Type Quantity Limit

Approval Criteria

Page 93

1 - Diagnosis of radiotherapy-induced nausea and vomiting

AND

2 - Patient is receiving radiotherapy consisting of total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen

AND

3 - Provider attests that a higher quantity is needed due to the number of radiation sessions

Product Name: Generic ondansetron 24 mg tablet, Generic ondansetron oral solution, Generic ondansetron ODT, Brand Zofran oral solution, or Zuplenz Diagnosis Hyperemesis gravidarum Approval Length 6 month(s) Guideline Type Quantity Limit

Approval Criteria

1 - Diagnosis of nausea and vomiting due to pregnancy (i.e., hyperemesis gravidarum) [10, 16]

AND

2 - History of failure, contraindication, or intolerance to at least one of the following: [A]

• doxylamine • metoclopramide (Reglan) • prochlorperazine (Compazine) • promethazine (Phenergan) • pyridoxine (Vitamin B6)

AND

3 - Patient has had at least a partial response to therapy at a dose within the quantity limit

Page 94

3 . Background

Benefit/Coverage/Program Information

Quantity Limit

These products are subject to a standard quantity limit. The quantity limit may vary from the standard limit based upon plan-specific benefit design. Please refer to your benefit materials.

4 . Endnotes

A. Treatment of nausea and vomiting of pregnancy with vitamin B6 or vitamin B6 plus doxylamine is safe and effective and should be considered first-line pharmacotherapy (Level A Evidence). Treatment of nausea and vomiting of pregnancy with ginger has shown beneficial effects and can be considered as a nonpharmacologic option (Level B Evidence). Several types of dopamine antagonists can be used for the treatment of nausea and vomiting of pregnancy such as promethazine, prochlorperazine, and metoclopramide. Antihistamines (such as dimenhydrinate and diphenhydramine) have been shown to be effective in controlling nausea and vomiting symptoms of pregnancy and are frequently used. Evidence is limited on the safety or efficacy of the 5-HT3 inhibitors (e.g. ondansetron) for nausea and vomiting of pregnancy. The ACOG recommends discussing the available data with patients as well as weighing the risks and benefits in women less than 10 weeks of gestation. Because of their limited data, they should not be advocated for first-line use until agents with established safety and efficacy have been tried and have failed. Treatment of severe nausea and vomiting of pregnancy or hyperemesis gravidarum with methylprednisolone may be efficacious in refractory cases; however, the risk profile of methylprednisolone suggests it should be a treatment of last resort (Level B Evidence). [16]

5 . References

1. Akynzeo prescribing information. Helsinn Therapeutics (U.S.), Inc. Iselin, NJ. May 2020. 2. Anzemet prescribing information. Validus Pharmaceuticals LLC. Parsippany, NJ. January 2019. 3. Emend prescribing information. Merck Sharp & Dohme Corp. Whitehouse Station, NJ. November 2019. 4. Granisetron prescribing information. Ascend Laboratories. Montvale, NJ. March 2011. 5. Marinol prescribing information. AbbVie Inc. North Chicago, IL. October 2019. 6. Sancuso prescribing information. Kyowa Kirin, Inc. Bedminster, NJ. June 2020. 7. Varubi prescribing information. Tesaro, Inc. Waltham, MA. March 2018.

Page 95 8. Zofran prescribing information. Novartis Pharmaceuticals Corporation. East Hanover, NJ. June 2020. 9. Zuplenz prescribing information. Fortovia Therapeutics, Inc. Raleigh, NC. May 2020. 10. Micromedex Healthcare Series [database on the Internet]. Greenwood Village (CO): Thomson Reuters (Healthcare) Inc.; Updated periodically. Available by subscription at: http://www.thomsonhc.com/. Accessed July 5, 2020. 11. Fauser AA, Russ W, Bischoff M. Oral dolasetron mesilate (MDL 73,147EF) for the control of emesis during fractionated total-body irradiation and high-dose cyclophosphamide in patients undergoing allogeneic bone marrow transplantation. Support Care Cancer. 1997 May;5(3):219-22. 12. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clinic Oncol. 2011;29(31):4189-98. 13. AHFS Drug Information website. Available at: https://online.lexi.com/lco/action/doc/retrieve/docid/250/413041. Accessed July 5, 2020. 14. Fujii Y, Tanaka H, Kawasaki T. Preoperative oral granisetron for the prevention of postoperative nausea and vomiting after breast surgery. Eur J Surg. 2001 Mar;167(3):184-7. 15. Fujii Y, Tanaka H, Kawasaki T. Prophylaxis with oral granisetron for the prevention of nausea and vomiting after laparoscopic cholecystectomy: a prospective randomized study. Arch Surg. 2001 Jan;136(1):101-4. 16. ACOG Practice Bulletin. Nausea and vomiting of pregnancy. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018; 103(1):15-30. 17. Cesamet prescribing information. Bausch Health US, LLC. Bridgewater, NJ. March 2020. 18. Sustol prescribing information. Heron Therapeutics. San Diego, CA. May 2017.

6 . Revision History

Date Notes

5/18/2021 Addition of EHB formulary to guideline, no changes to criteria

Page 96 Antipsoriatic Agents

Prior Authorization Guideline

GL-15893 Antipsoriatic Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 3/19/1998; P&T Revision Date: 2/25/2016

1 . Indications Drug Name: 8-MOP (methoxsalen) Psoriasis Photochemotherapy (methoxsalen with long wave ultraviolet light) is indicated for the symptomatic control of severe, recalcitrant, disabling psoriasis not adequately responsive to other forms of therapy and when the diagnosis has been supported by biopsy. Methoxsalen is intended to be administered only in conjunction with a schedule of controlled doses of long wave ultraviolet radiation.

Vitiligo Indicated for photochemotherapy (methoxsalen with long wave ultraviolet light) for the repigmentation of idiopathic vitiligo.

Cutaneous T-cell Lymphoma Indicated for photopheresis (methoxsalen with long wave ultraviolet radiation of white blood cells) for use with UVAR System in the palliative treatment of

Page 97 the skin manifestations of cutaneous T-cell lymphoma (CTCL) in persons who have not been responsive to other forms of treatment. While this dosage form of methoxsalen has been approved for use in combination with phtopheresis, Oxsoralen Ultra capsules have not been approved for that use.

Drug Name: Calcitrene (calcipotriene) ointment Psoriasis Indicated for the treatment of plaque psoriasis in adults.

Drug Name: Oxsoralen (methoxsalen) lotion Vitiligo Used as topical repigmenting agent in conjunction with controlled doses of ultraviolet A (320-400 nm) or sunlight.

Off Label Uses: Psoriasis Used in the treatment of psoriasis when combined with UVA. [1]

Drug Name: Oxsoralen Ultra (methoxsalen) capsules Psoriasis Photochemotherapy (methoxsalen with long wave ultraviolet light) is indicated for the symptomatic control of severe, recalcitrant, disabling psoriasis not adequately responsive to other forms of therapy and when the diagnosis has been supported by biopsy. Methoxsalen is intended to be administered only in conjunction with a schedule of controlled doses of long wave ultraviolet radiation.

Off Label Uses: Vitiligo Several studies have indicated the efficacy of PUVA therapy with methoxsalen in the treatment of vitiligo. [1,7,8] Oral methoxsalen is usually administered for repigmentation of idiopathic vitiligo prior to UVA light. [1]

Cutaneous T-cell Lymphoma Methoxsalen in combination with photopheresis is indicated in the palliative treatment of skin manifestations of cutaneous T-cell lymphoma in patients unresponsive to other treatments. [1]

Drug Name: Sorilux (calcipotriene) foam Psoriasis Indicated for the topical treatment of plaque psoriasis of the scalp and body in patients 18 years and older.

Drug Name: Taclonex (calcipotriene/betamethasone) ointment Psoriasis Indicated for the topical treatment of plaque psoriasis in patients 12 years of age and older.

Drug Name: Taclonex (calcipotriene/betamethasone) suspension Psoriasis Indicated for the topical treatment of plaque psoriasis of the scalp and body in patients 18 years and older, and for the topical treatment of the scalp in patients age 12 to 17 years.

Drug Name: Enstilar (calcipotriene and betamethasone dipropionate) foam

Page 98 Plaque psoriasis Indicated for the topical treatment of plaque psoriasis in patients 18 years of age and older.

2 . Criteria

Product Name: Generic calcipotriene ointment, Generic calcipotriene/betamethasone, Brand Calcitrene, Sorilux foam, Brand Taclonex ointment, or Taclonex suspension Diagnosis Psoriasis Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - Diagnosis of psoriasis

AND

2 - History of failure, contraindication, or intolerance to two medium to high potency corticosteroid topical treatments (See Table 1 in Background section)

AND

3 - History of failure, contraindication, or intolerance to generic calcipotriene cream or solution

Product Name: Oxsoralen lotion Diagnosis Psoriasis or Vitiligo Approval Length 12 Month Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

Page 99 • Psoriasis (off-label) [1] • Vitiligo

AND

2 - Used in conjunction with PUVA therapy

AND

3 - Prescribed by a dermatologist

AND

4 - History of failure, contraindication, or intolerance to two medium to high potency corticosteroid topical treatments (See Table 1 in Background section)

Product Name: 8-MOP, Generic methoxsalen, or Brand Oxsoralen Ultra Diagnosis Psoriasis or Vitiligo Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - One of the following diagnoses:

• Psoriasis • Vitiligo [1,7,8]

AND

2 - Used in conjunction with PUVA therapy

AND

Page 100

3 - History of failure, contraindication, or intolerance to three medium to high potency corticosteroid topical treatments (See Table 1 in Background section)

Product Name: 8-MOP, Generic methoxsalen (off-label), or Brand Oxsoralen Ultra (off-label) Diagnosis Cutaneous T-cell lymphoma Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - Diagnosis of cutaneous T-cell lymphoma [1]

Product Name: Enstilar Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of psoriasis vulgaris/plaque psoriasis

AND

2 - History of failure or intolerance to both of the following USED CONCURRENTLY:

• A medium to high potency topical steroid (See Table 1 in Background section) • A Vitamin D analog

Product Name: Enstilar Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 101

Approval Criteria

1 - Patient has responded to therapy (e.g., symptoms have improved)

3 . Background

Clinical Practice Guidelines

Table 1. Relative Potency of Selected Topical Corticosteroid Products

Drug Dosage Form Strength Very High Potency Augmented betamethasone Ointment 0.05% dipropionate (Diprolene)* Clobetasol propionate Ointment 0.05% (Temovate)* Diflorasone diacetate (Psorcon) Ointment 0.05% Halobetasol propionate (ultravate) Cream, Ointment 0.05%

High Potency Amcinonide (Cyclocort) Cream, Lotion, 0.1% Ointment Augmented betamethasone Cream 0.05% dipropionate (Diprolene, Diprolene AF)* Betamethasone dipropionate Cream, Ointment 0.05% (Diprosone)* Betamethasone valerate Ointment 0.1% (Valisone)* Desoximetasone (Topicort)* Cream, Ointment 0.25% Gel 0.05% Diflorasone diacetate (Florone, Cream, Ointment 0.05% Maxiflor) (emollient base) Fluocinolone acetonide (Synalar)* Cream 0.2% Fluocinonide (Lidex)* Cream, Ointment, Gel 0.05% Halcinonide (Halog) Cream, Ointment 0.1%

Medium Potency Betamethasone dipropionate Lotion 0.05% (Diprosone)* Betamethasone valerate Cream 0.1%

Page 102 (Valisone)* Betamethasone valerate (Luxiq) Foam 0.12% Clocortolone pivalate (Cloderm) Cream 0.1% Desoximetasone (Topicort)* Cream 0.05% Fluocinolone acetonide (Synalar)* Cream, Ointment 0.025% Flurandrenolide (Cordran) Cream, Ointment 0.025% Cream, Ointment, 0.05% Lotion Fluticasone propionate Cream 0.05% (Cutivate)* Ointment 0.005% Hydrocortisone butyrate (Locoid)* Ointment, Solution 0.1% Hydrocortisone butyrate Cream, Ointment 0.2% (Westcort)* Mometasone furoate (Elocon)* Cream, Ointment, 0.1% Lotion Triamcinolone acetonide Cream, Ointment, 0.025% (Aristocort, Kenalog)* Lotion 0.1% Cream, Ointment, Lotion

Reference: Corticosteroids Topical Monograph, Facts and Comparisons 2007

* Formulary Topical corticosteroids

4 . References

1. Micromedex [Internet database]. Greenwood Village, Colo: Truven Health Analytics. Updated periodically. Accessed January 9, 2015. 2. National Psoriasis Foundation. About psoriasis. Statistics. Available at http://www.psoriasis.org/about/stats/. Accessed on April 2nd 2009 3. McEvoy GK. AHFS Drug Information 2010. Bethesda, MD: American Society of Health- System Pharmacists, Inc; 2010. 4. Drugs for Acne, Rosacea and Psoriasis. Treatment guidelines from the Medical Letter. 2005. 3(35): 49-56. 5. American Academy of Dermatology. Psoriasis. Available at: https://www.aad.org/education/clinical-guidelines. Accessed January 9, 2015. 6. Mentor A, Korman N, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. Amer. Acad. of Derm. 2009;60:643-59. 7. Parrish JA, Fitzpatrick TB, Shea C, et al: Photochemotherapy of vitiligo: use of orally administered psoralens and high-intensity long-wave ultraviolet light system. Arch Dermatol 1976; 112(11):1531-1534.

Page 103 8. Pathak MA, Mosher DB, Fitzpatrick TB. Safety and therapeutic effectiveness of 8- methoxypsoralen, 4,5,8-trimethylpsoralen, and psoralen in vitiligo. Natl Cancer Inst Monogr. 1984;66165-73. 9. 8-MOP Prescribing Information. Valeant Pharma, August 2010. 10. Oxsoralen Prescribing Information. Valeant Pharma, April 2014. 11. Oxsoralen Ultra Prescribing Information. Valeant Pharma, November 2011. 12. Taclonex Ointment Prescribing Information. Leo Pharma, December 2014. 13. Taclonex Topical Suspension Prescribing Information. Leo Pharma, September 2014. 14. Enstilar prescribing information. LEO Pharma, Inc. October 2015.

Page 104 Apidra (insulin glulisine)

Prior Authorization Guideline

GL-5873 Apidra (insulin glulisine)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 8/2/2004; CPS Revision Date: 8/21/2012 According to Texas State Law, all diabetic medications used for the treatment of diabetes shall be covered.

1 . Indications Drug Name: Apidra (insulin glulisine) Diabetes Mellitus [1] Is indicated to improve glycemic control in adults and children with diabetes mellitus.

2 . Criteria

Product Name: Apidra or, if covered, Apidra SoloStar*

Page 105 Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following:

• Humalog (insulin lispro)† • Novolog (insulin aspart)†

Notes *For plans that provide coverage for insulin vials only, see separate “In sulin Delivery Systems” administrative guideline for criteria. †Per the A merican Geriatric Society 2012 Beers Criteria Update, sliding-scale ins ulin (eg, insulin dose based on pre-defined blood glucose ranges) shou ld be avoided in patients greater than or equal to 65 years of age. [a]

3 . Background

Clinical Practice Guidelines

American Diabetes Association (2012) [5, 8, 9]

Overall key points

• Glycemic targets and glucose-lowering therapies must be individualized.

• Diet, exercise and education remain the foundation of any T2DM regimen program.

• Unless there are prevalent contraindications, metformin is the optimal first-line drug.

• After metformin, there are limited data for guidance. Combination therapy with additional 1-2 oral or injectable agents is reasonable, aiming to minimize side effects where possible.

• Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain glucose control.

• All treatment decisions, where possible, should be made in conjunction with the patient, focusing on his/her preferences, needs and values.

Page 106 • Comprehensive CV risk reduction must be a major focus of therapy.

Initial drug therapy

• Specific patient preferences, characteristics, susceptibilities to side effects, potential for weight gain, and hypoglycemia should play a major role in drug selection.

• Metformin is the preferred and most cost-effective agent.

• If metformin cannot be used, another oral agent could be chosen, such as a SFU/glinide, pioglitazone, or a DPP-4 inhibitor. In occasional cases where weight loss is an essential aspect of therapy, initial treatment with a GLP-1 receptor agonist might be useful.

• Less commonly used drugs (ie, AGIs, colesevelam, bromocriptine) might be considered in selected patients, but their modest glycemic effects and side-effect profiles make them less attractive candidates.

Advancing to dual combination therapy

• If monotherapy alone does not achieve or maintain an A1C target over ~3 months, then next step would be to add a second oral agent, a GLP-1 receptor agonist, or basal insulin.

• On average any second agent is typically associated with an approximate further reduction in A1C of ~1%. If no clinically meaningful reduction (ie, non-responder) is demonstrated, then, adherence having been investigated, that agent should be discontinued, and another agent with a different mechanism of action substituted.

• With a distinct paucity of long-term comparative effectiveness trials available, uniform recommendations or the best agent combined with metformin cannot be made. Thus the advantages and disadvantages of specific drugs for each patient should be considered.

Advancing to triple combination therapy

• The essential consideration is to use agents with complementary mechanisms of action.

• Some studies have shown advantages of adding a third noninsulin agent to a two-drug combination that is not yet or no longer achieving the glycemic target. However, at this juncture, the most robust response will usually be with insulin.

Page 107 American Association of Clinical Endocrinologists/American College of Endocrinology (2009) [7,10]

The AACE/ACE recommends achieving an A1C of less than or equal to 6.5%, with an emphasis on minimizing the risk of hypoglycemia and weight gain. The AACE/ACE algorithm is stratified by the patient’s current A1C level and, as with the ADA, positions lifestyle modifications and metformin as first-line therapy.

In patients with an A1C of 7.5% or lower, initial monotherapy with metformin or, alternatively, a DPP-4 inhibitor, GLP-1 receptor agonist, TZD, or AGI, is recommended. If monotherapy fails to achieve the A1C goal of less than or equal to 6.5%, then dual therapy should be started by adding one of the following agents in this preferential order based on hypoglycemia risk: GLP-1 receptor agonist, DDP-4 inhibitor, TZD, glinide, or SU. When metformin is contraindicated or not tolerated, a TZD with either a GLP-1 receptor agonist or DPP-4 inhibitor may be used. Two additional second-line therapy options included in the algorithm for this A1C group only are colesevelam and AGI. These agents are included because of their minimal risk of hypoglycemia and the ability of colesevelam to lower the LDL cholesterol levels. If dual therapy fails, then triple therapy or insulin therapy should be started.

In patients with an A1C between 7.6% and 9.0%, one should begin with dual therapy because monotherapy is unlikely to be successful in this group. Metformin is again the foundation of therapy with either a GLP-1 agonist or a DPP-4 inhibitor as the preferred second component due to their low risk of hypoglycemia, efficacy in reducing postprandial glucose excursions, and beneficial or neutral effect on weight. Alternatively, a TZD, SU, or glinide may be used in this preferential order as second components of the dual therapy when the incretin-based therapies would not be appropriate. If dual therapy does not achieve the A1C goal, then triple therapy or insulin therapy should be started.

In patients with an A1C > 9.0%, therapy is recommended based on the patient’s prior treatment history and whether or not symptoms are present. If the patient is asymptomatic, particularly with a relatively recent onset of diabetes, a good probability exists for preservation of some endogenous beta cell function, implying that dual therapy or triple therapy may be sufficient. In contrast, if the patient is symptomatic with polydipsia, polyuria, and weight loss, or if the patient has already been receiving treatment and regimens similar to the aforementioned ones have failed, then it is appropriate to initiate insulin therapy without delay.

4 . Endnotes

Page 108 A. Sliding-scale insulin is included in the 2012 American Geriatrics Society Beers Criteria list of inappropriate medications in older adults (greater than or equal to 65 years old). [11]

5 . References

1. Apidra Prescribing Information. Sanofi Aventis, February 2009. 2. Hermansen K, Fontaine P, Kukolja KK, Peterkova V, Leth G, Gall MA. Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes. Diabetologia. 2004; 47(4): 622-9. 3. Dailey G, Rosenstock J, Moses RG, Ways K. Insulin Glulisine Provides Improved Glycemic Control in Patients With Type 2 Diabetes. Diabetes Care 2004 (27): 2363- 2368. 4. Dreyer M, Prager R, Robinson A, et al. Efficacy and safety of insulin glulisine in patients with type 1 diabetes. Horm Metab Res. 2005;37(11):702-7. 5. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2010;33(suppl 1):S11-S61. 6. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32(1):193-203. 7. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract 2007;13(suppl 1):3-68. 8. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2012; 35 (suppl 1): S11-S63. 9. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient centered approach. Diabetes Care. 2012, 19 April 2012 [Epub ahead of print] 10. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559. 11. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. AGS updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012.

Page 109 Asacol HD (mesalamine tablet, delayed-release) and Delzicol (mesalamine capsule, delayed-release) - NonFormulary or Step Therapy

Prior Authorization Guideline

GL-61738 Asacol HD (mesalamine tablet, delayed-release) and Delzicol (mesalamine capsule, delayed-release) - NonFormulary or Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2020 P&T Approval Date: 11/15/2019

P&T Revision Date:

1 . Indications Drug Name: Asacol HD (mesalamine tablet, delayed release) Ulcerative colitis Indicated for the treatment of moderately active ulcerative colitis in adults.

Drug Name: Delzicol (mesalamine capsule, delayed release) Ulcerative colitis Indicated for the treatment of mildly to moderately active ulcerative colitis in patients 5 years of age and older and for the maintenance of remission of ulcerative colitis in adults.

2 . Criteria

Page 110 Product Name: Asacol HD or Delzicol Approval Length 12 month(s) Guideline Type NonFormulary or Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to both of the following:

• Apriso • Lialda

3 . Background

Benefit/Coverage/Program Information

Background:

Asacol HD (mesalamine tablet, delayed release) is indicated for the treatment of moderately active ulcerative colitis in adults.

Delzicol (mesalamine capsule, delayed release) is indicated for the treatment of mildly to moderately active ulcerative colitis in patients 5 years of age and older and for the maintenance of remission of ulcerative colitis in adults.

Apriso (mesalamine capsule, extended release) is indicated for the maintenance of remission of ulcerative colitis in patients 18 years of age and older.

Lialda (mesalamine tablet, delayed release) is indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis and for the maintenance of remission of ulcerative colitis.

This program requires a patient trial of Apriso and Lialda before providing coverage for Asacol HD or Delzicol.

Additional Clinical Rules:

Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and re-authorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

Page 111

4 . References

1. Apriso [package insert]. Bridgewater, NJ: Salix Pharmaceuticals; March 2019. 2. Asacol HD [package insert]. Madison, NJ: Allergan USA, Inc.; April 2018. 3. Delzicol [package insert]. Madison, NJ: Allergan USA, Inc.; January 2019. 4. Lialda [package insert]. Shire Way, Lexington, MA: Shire US Inc.; July 2019.

5 . Revision History

Date Notes

1/31/2020 11/2019 - New program.

Page 112 Atelvia (risedronate delayed-release)

Prior Authorization Guideline

GL-30083 Atelvia (risedronate delayed-release)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 11/20/1998; P&T Revision Date: 6/22/2016. **Effective 7/1/2016**

1 . Indications Drug Name: Atelvia (risedronate delayed-release tablets) Postmenopausal osteoporosis Indicated for the treatment of osteoporosis in postmenopausal women. In postmenopausal women, risedronate sodium reduces the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis-related fractures. Important Limitations of Use: The optimal duration of use has not been determined. The safety and effectiveness of Atelvia for the treatment of osteoporosis are based on clinical data of one year duration. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.

Page 113

2 . Criteria

Product Name: Brand Atelvia, Generic risedronate delayed-release Guideline Type Step Therapy

Approval Criteria

1 - History of alendronate or alendronate solution

3 . Background

Benefit/Coverage/Program Information

Quantity Limit

This product is subject to a standard quantity limit. The quantity limit may vary from the standard limit based upon plan-specific benefit design. Please refer to your benefit materials.

4 . References

1. Harris ST et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 1999;282:1344-52. 2. Reginster J et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporosis Int 2000;11(1):83- 91. 3. McClung MR et al. Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort (EPIC) study. J Clin Endocrinol Metab 2004;89:4879-85. 4. Chesnut CH, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19:1241-1249 5. Miller PD et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1- year results from the MOBILE study. J Bone Miner Res 2005;20:1315-1322. 6. Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med. 1990 3;322:1265-71. 7. Black DM et al. Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996;348(9041):1535-1541.

Page 114 8. Cummings SR et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: Results from the fracture intervention trial. JAMA 1998;280(24):2077-2082. 9. McClung MR et al. Effect of risedronate on the risk of hip fractures in elderly women. N Engl J Med 2001;344(5):333-340. 10. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000;343(9)604-610. 11. Cohen S et al. Risedronate therapy prevents corticosteroid-induced bone loss. Arthritis Rheum 1999;42(11):2309-18. 12. Saag KG et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 1998;339(5):292-299. 13. Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med. 1997;337:382-7. 14. Miller PD et al. A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget’s disease of bone. Am J Med 1999;106(5):513-520. 15. Reid IR et al. Biochemical and radiologic improvement in Paget’s disease of bone treated with alendronate: A randomized, placebo-controlled trial. Am J Med 1996;101(4):341-348. 16. Banovac K, Gonzalez F. Evaluation and management of heterotopic ossification in patients with spinal cord injury. Spinal Cord. 1997;35:158-62. 17. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Available at: http://www.aace.com/pub/pdf/guidelines/osteoporosis2001Revised.pdf. Accessed May 1, 2006. 18. National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis. Washington (DC): National Osteoporosis Foundation; 2003. 19. Dugdale DC, Vyas JM, Zieve D. Alkaline phosphatase isoenzyme test. Medline Plus Web Site. http://www.nlm.nih.gov/medlineplus/ency/article/003497.htm. Updated May 7, 2009. Accessed December 28, 2009. 20. DRUGDEX System [Internet database].Greenwood Village, Colo: Thomson Micromedex. Updated periodically. Accessed February 5, 2010. 21. Atelvia Prescribing Information. Warner Chilcott. March 2015.

Page 115 Azole Antifungals

Prior Authorization Guideline

GL-87331 Azole Antifungals

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 10/20/1998 P&T Revision Date: 11/14/2019 ; 02/13/2020 ; 02/18/2021 ; 02/18/2021

1 . Indications Drug Name: Sporanox (itraconazole) capsules Blastomycosis Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary

Histoplasmosis Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis

Aspergillosis Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or refractory to amphotericin B therapy

Onychomycosis of the toenail Indicated for the treatment of the following fungal infection in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (Tinea unguium)

Onychomycosis of the fingernail Indicated for the treatment of the following fungal infection

Page 116 in non-immunocompromised patients: Onychomycosis of the fingernail due to dermatophytes (Tinea unguium)

Drug Name: Sporanox Pulse Pak (itraconazole) Onychomycosis of the fingernail Indicated for the treatment of the following fungal infection in non-immunocompromised patients: Onychomycosis of the fingernail due to dermatophytes (Tinea unguium)

Drug Name: Sporanox (itraconazole) oral solution Oropharyngeal and esophageal candidiasis Indicated for the treatment of oropharyngeal and esophageal candidiasis.

Drug Name: Tolsura (itraconazole) capsules Blastomycosis Indicated for the treatment of the following fungal infection in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary.

Drug Name: Noxafil (posaconazole) tablets Aspergillus infection Indicated for prophylaxis of invasive Aspergillus infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Candida infection Indicated for prophylaxis of invasive Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Drug Name: Noxafil (posaconazole) oral suspension Aspergillus infection Indicated for prophylaxis of invasive Aspergillus infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Candida infection Indicated for prophylaxis of invasive Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as

Page 117 HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Oropharyngeal candidiasis Indicated for treatment of oropharyngeal candidiasis (OPC), including OPC refractory (rOPC) to itraconazole and/or fluconazole.

2 . Criteria

Product Name: Brand Sporanox capsules or generic itraconazole capsules Diagnosis Systemic and topical fungal infections Approval Length 6 months [5, 10-12, B-D] Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of a systemic fungal infection (e.g., aspergillosis, histoplasmosis, blastomycosis)

2 - All of the following:

2.1 One of the following diagnoses:

• Tinea corporis (ring worm) • Tinea cruris (jock itch) • Tinea pedis (athlete's foot) • Tinea capitis (scalp ringworm) • Pityriasus versicolor

AND

2.2 One of the following:

2.2.1 The tinea infection is resistant to topical antifungal treatment

Page 118 OR

2.2.2 Trial and failure, contraindication, or intolerance to oral terbinafine [3]

Product Name: Brand Sporanox capsules, generic itraconazole capsules, or Sporanox Pulse Pak Diagnosis Onychomycosis - Fingernails Approval Length 1 Month [A] Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of fingernail onychomycosis as confirmed by one of the following:

• Positive potassium hydroxide (KOH) preparation • Fungal culture • Nail biopsy

AND

2 - The patient’s condition is causing debility or a disruption in their activities of daily living (e.g., limitations to manual dexterity, wearing shoes, or appropriately manicuring nails) [4]

AND

3 - Trial and failure, contraindication, or intolerance to oral terbinafine

Product Name: Brand Sporanox capsules or generic itraconazole capsules Diagnosis Onychomycosis - Toenails Approval Length 3 Month [A] Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of toenail onychomycosis as confirmed by one of the following:

Page 119 • Positive potassium hydroxide (KOH) preparation • Fungal culture • Nail biopsy

AND

2 - The patient’s condition is causing debility or a disruption in their activities of daily living (e.g., limitations to manual dexterity, walking, standing, wearing shoes, or appropriately manicuring nails) [4]

AND

3 - Trial and failure, contraindication, or intolerance to oral terbinafine

Product Name: Brand Sporanox oral solution or generic itraconazole oral solution Diagnosis Candidiasis (esophageal or oropharyngeal) Approval Length 1 month [E, F] Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Diagnosis of esophageal candidiasis

1.2 Diagnosis of oropharyngeal candidiasis (OPC)

AND

2 - Candidiasis is refractory to treatment with fluconazole [E]

Product Name: Tolsura

Page 120 Approval Length 6 months [5, 10-12, B-D] Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of one of the following fungal infections:

• Blastomycosis • Histoplasmosis • Aspergillosis

AND

2 - Trial and failure or intolerance to generic itraconazole capsules

Product Name: Brand Noxafil oral tablet, generic posaconazole oral tablet, Brand Noxafil oral suspension Diagnosis Systemic fungal infections Approval Length 6 Months [B-D] Guideline Type Prior Authorization

Approval Criteria

1 - Used as prophylaxis of invasive fungal infections caused by one of the following:

• Aspergillus • Candida

AND

2 - One of the following:

2.1 Patient is at high risk of infections due to severe immunosuppression from one of the following conditions:

• Hematopoietic stem cell transplant (HSCT) with graft-versus-host disease (GVHD) • Hematologic malignancies with prolonged neutropenia from chemotherapy

Page 121

2.2 Patient has a prior fungal infection requiring secondary prophylaxis [15, G]

Product Name: Brand Noxafil oral tablet, generic posaconazole oral tablet, Brand Noxafil oral suspension Diagnosis Oropharyngeal Candidiasis Approval Length 1 Month [E] Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of oropharyngeal candidiasis (OPC)

AND

2 - Candidiasis is refractory to treatment with fluconazole [E]

3 . Endnotes

A. Fingernail infections are usually reevaluated 18 weeks or longer after completion of therapy. Toenail infections are usually reevaluated 6-9 months after completion of therapy. [5] Indeed, considering that toenails can take 12 to 18 months to grow out, many clinicians consider that 1 year is too short to assess clinical effectiveness. [6] Reports of long-term follow-up of treated patients have recently been presented, suggesting that positive mycology at 12 and 24 weeks after commencement of therapy are poor prognostic signs and may indicate a need for retreatment or for a change of drug. [8] B. The optimal duration of therapy for aspergillosis has not been defined. Most clinicians treat infections (pulmonary) until resolution or stabilization of clinical and radiographic manifestations. The IDSA recommends a minimal treatment period of 6 – 12 weeks in immunocompetent patients for invasive conditions. [11] C. According to the IDSA guidelines for aspergillosis, duration of therapy for most conditions for aspergillosis has not been optimally defined. Most experts attempt to treat pulmonary infection until resolution or stabilization of all clinical and radiographic manifestations. Other factors include site of infection (e.g., osteomyelitis), level of immunosuppression, and extent of disease. Reversal of immunosuppression, if feasible, is important for a favorable outcome for invasive aspergillosis.” [11]

Page 122 D. According to the IDSA guidelines for the treatment of aspergillosis, both Amphotericin B and itraconazole are listed as second line treatment options for the treatment of invasive disease. [11] E. For fluconazole-refractory OPC, either itraconazole or posaconazole for up to 28 days is recommended. For fluconazole-refractory esophageal candidiasis, itraconazole or voriconazole for 14 to 21 days is recommended. [3, 5] F. Patients may be expected to relapse shortly after discontinuing therapy with Sporanox oral solution. Limited data on the safety of long-term use (> 6 months) of Sporanox Oral Solution are available at this time. [2] G. NCCN recommends secondary prophylaxis with an appropriate antifungal agent in patients with prior chronic disseminated candidiasis or with invasive filamentous fungal infection during subsequent cycles of chemotherapy or HSCT. In patients with invasive aspergillosis before HSCT, antifungal therapy for more than a month and resolution of radiologic abnormalities correlate with a lower likelihood of post-transplant recurrence of infection. Secondary prophylaxis with a mold-active agent is advised for the entire period of immunosuppression. Secondary prophylaxis is generally administered for the duration of immunosuppression. Per recommendation from an infectious disease specialist, posaconazole is used for secondary prophylaxis of prior fungal infections. [15]

4 . References

1. Sporanox Capsules Prescribing Information. Janssen Pharmaceuticals, Inc.; Titusville, NJ. December 2019. 2. Sporanox Oral Solution Prescribing Information. Janssen Pharmaceuticals, Inc.; Titusville, NJ. April 2019. 3. Ely J, Rosenfeld S, Stone M. Diagnosis and Management of Tinea Infections. Aafp.org. https://www.aafp.org/afp/2014/1115/p702.html. Published 2014. Accessed October 28, 2019 4. Gupta A, Mays R. The Impact of Onychomycosis on Quality of Life: A Systematic Review of the Available Literature. Skin Appendage Disord. 2018;4(4):208-216. doi:10.1159/000485632 5. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-50. 6. Stevens DA, Kan VL, Judson MA, et al. Practice Guidelines for Diseases Caused by Aspergillus. Clin Infect Dis. 2000;30:696-709. 7. McEvoy GK. AHFS Drug Information 2005. Bethesda, MD: American Society of Health- System Pharmacists, Inc; 2005. 8. Sigurgeirsson B, Olafsson JH, Steinsson JP, et al. Long-term effectiveness of treatment with terbinafine vs. itraconazole in onychomycosis: a 5-year blinded prospective follow- up study. Arch Dermatol. 2002;138:353-7. 9. Roberts DT, Taylor WD, Boyle J. Guidelines for treatment of onychomycosis. Br J Dermatol. 2003;148:402-410. 10. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801-1812.

Page 123 11. Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807-825. 12. Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of Aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-60. 13. Tolsura Prescribing Information. Mayne Pharma; Greenville, NC. June 2020. 14. Noxafil Prescribing Information. Merck Sharp & Dohme Corp.; Whitehouse Station, NJ. September 2020. 15. Per Clinical Consultation with an Infectious Disease Specialist. January 24, 2014.

5 . Revision History

Date Notes

5/20/2021 Addition of EHB formulary to guideline, no changes to criteria

Page 124 Basal Insulin

Prior Authorization Guideline

GL-85962 Basal Insulin

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 8/8/2016 P&T Revision Date: 06/17/2020 ; 10/21/2020 ; 6/16/2021

1 . Indications Drug Name: Basaglar (insulin glargine) Diabetes Mellitus Indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Limitations of use: Not recommended for the treatment of diabetic ketoacidosis.

Drug Name: Semglee (insulin glargine) Diabetes Mellitus Indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Limitations of use: Not recommended for the treatment of diabetic ketoacidosis.

2 . Criteria

Page 125 Product Name: Basaglar, Semglee Diagnosis Diabetes mellitus Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - Trial of a 30 day supply to two of the following:

• Lantus (insulin glargine) • Levemir (insulin detemir) • Toujeo (insulin glargine) [A] • Tresiba (insulin degludec)

3 . References

1. Basaglar Prescribing Information. Lilly USA, LLC. Indianapolis, IN. November 2019. 2. Garber AJ, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive diabetes management algorithm – 2018 executive summary. https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf. Accessed May 27,2020. 3. Semglee Prescribing Information. Mylan Specialty, Morgantown, WV. June 2020.

4 . Revision History

Date Notes

5/21/2021 Annual Review: updated semglee indication section and updated refer ences - no changes to criteria

Page 126 Belbuca (buprenorphine hydrochloride film) and Butrans (buprenorphine patch, extended-release) - PA/Med Nec

Prior Authorization Guideline

GL-78096 Belbuca (buprenorphine hydrochloride film) and Butrans (buprenorphine patch, extended-release) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 8/19/2016 P&T Revision Date: 11/15/2019 ; 11/13/2020

1 . Indications Drug Name: Belbuca (buprenorphine) buccal film, Butrans^ (buprenorphine) transdermal patch Pain Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.

2 . Criteria

Product Name: Belbuca [a] Diagnosis Cancer or End of Life (defined as a < 2 year life expectancy) related pain [b]

Page 127 Approval Length 24 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Patient is being treated for pain due to active cancer diagnosis or end-of-life related pain (document cancer diagnosis for end of life, expectancy of less than 2 years)

AND

2 - Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Coverage of medications used to treat stage four advanced meta static cancer or associated conditions (e.g., cancer pain) may be appro ved based on state mandates.

Product Name: Butrans^ [a] Diagnosis Cancer or End of Life (defined as a < 2 year life expectancy) related pain [b] Approval Length 24 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Patient is being treated for pain due to active cancer diagnosis or end-of-life related pain (document cancer diagnosis for end of life, expectancy of less than 2 years)

AND

2 - The patient has a history of failure after a 30 day trial, contraindication or intolerance to Belbuca [c]

Page 128 AND

3 - Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Coverage of medications used to treat stage four advanced meta static cancer or associated conditions (e.g., cancer pain) may be appro ved based on state mandates. [c] In Connecticut, trial must be a generi c product. ^ Butrans is typically excluded from coverage. Tried/Failed c riteria may be in place. Please refer to plan specifics to determine excl usion status.

Product Name: Belbuca [a] Diagnosis Non-cancer pain Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - The patient is being treated for pain severe enough to require daily, around-the-clock, longer-term opioid treatment

AND

2 - Prescriber attests to all of the following:

• The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided. • Pain is moderate to severe and expected to persist for an extended period of time • Pain is chronic • Medication is not being used for opioid dependence • Dose does not exceed the maximum recommended dose per product label. (See Table 1)

Page 129 AND

3 - The patient is not receiving other long-acting opioids concurrently Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Butrans^ [a] Diagnosis Non-cancer pain Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - The patient is being treated for pain severe enough to require daily, around-the-clock, longer-term opioid treatment

AND

2 - Prescriber attests to all of the following:

AND

3 - The patient is not receiving other long-acting opioids concurrently

Page 130 AND

4 - The patient has a history of failure after a 30 day trial, contraindication or intolerance to a trial BOTH of the following [c]:

• Belbuca • tramadol (e.g. Ultram ER)

Notes ^Butrans is typically excluded from coverage. Tried/Failed criteria may be in place. Please refer to plan specifics to determine exclusion status . [a] State mandates may apply. Any federal regulatory requirements a nd the member specific benefit plan coverage may also impact coverag e criteria. Other policies and utilization management programs may ap ply. [c] In Connecticut, trial must be a generic product.

Product Name: [Belbuca or Butrans^] [a] Diagnosis Non-cancer pain Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - All of the following

1.1 Prescriber attests to ALL of the following:

• Treatment goals are defined, including estimated duration of treatment. • Treatment plan includes the use of a non-opioid analgesic and/or non-pharmacologic intervention • Patient has been screened for substance abuse/opioid dependence • If used in patients with medical comorbidities or if used concurrently with a benzodiazepine or other drugs that could potentially cause drug-drug interactions, the prescriber has acknowledged that they have completed an assessment of increased risk for respiratory depression. • The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided. • Pain is moderate to severe and expected to persist for an extended period of time • Pain is chronic • Pain is not postoperative (unless the patient is already receiving chronic opioid therapy prior to surgery, or if the postoperative pain is expected to be moderate to severe and

Page 131 persist for an extended period of time)

AND

1.2 Patient demonstrates meaningful improvement in pain and function (Document improvement in function or pain score improvement)

AND

1.3 Identify rationale for not tapering and discontinuing opioid. (Document rationale)

AND

2 - Dose does not exceed maximum dose recommended by product label (see Table 1). (Document total daily dose). Notes ^Butrans is typically excluded from coverage. Tried/Failed criteria may be in place. Please refer to plan specifics to determine exclusion status . [a] State mandates may apply. Any federal regulatory requirements a nd the member specific benefit plan coverage may also impact coverag e criteria. Other policies and utilization management programs may ap ply.

3 . Background

Clinical Practice Guidelines

CDC and the American Academy of Neurology The CDC and the American Academy of Neurology recommend the following best practices in the prescription of long-acting opioids:

• Non-pharmacologic therapy and non-opioid pharmacologic therapy are preferred for chronic pain. • Before starting opioid therapy, treatment goals should be established with patients that include realistic goals for pain and function and should consider how therapy will be discontinued if benefits do not outweigh risks.Track pain and function at every visit (at least every 3 months) using a brief, validated instrument.Continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. • When starting opioid therapy for chronic pain, clinicians should prescribe immediate-

Page 132 release opioids instead of extended-release/long-acting opioids. • Document the daily morphine equivalent dose (MME) in mg/day from all sources of opioids.Access the state prescription drug monitoring program (PDMP) data at treatment initiation and periodically during treatment.Currently all states except for Missouri have a PDMP. • To avoid increased risk of respiratory depression, long-acting opioids should not be prescribed concurrently with benzodiazepines. • Screen for past and current substance abuse and for severe depression, anxiety, and PTSD prior to initiation. • Use random urine drug screening prior to initiation and periodically during treatment with a frequency according to risk. • Use a patient treatment agreement, signed by both the patient and prescriber, that addresses risks of use and responsibilities of the patient. • Methadone should not be the first choice for a long-acting opioid.Only clinicians who are familiar with methadone’s unique risk profile and who are prepared to educate and closely monitor their patients should consider prescribing methadone for pain. • Avoid escalating doses above 50-90 mg/day MME unless sustained meaningful improvement in pain and function is attained, and not without consultation with a pain management specialist. • Clinicians should evaluate benefits and harms of continued therapy at least every 3 months.If benefits do not outweigh harms, opioids should be tapered and discontinued.Evaluation should include assessment of substance use disorder/opioid dependence.Validated scales (such as the DAST-10) are available at www.drugabuse.gov. Benefit/Coverage/Program Information

Additional Clinical Rules:

^Butrans is typically excluded from coverage. Tried/Failed criteria may be in place. Please refer to plan specifics to determine exclusion status.

Background: Belbuca and Butrans^ are buprenorphine products indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. Similar to other long-acting opioids, the use of Butrans^ and Belbuca should be reserved for use in patients for whom alternative treatment options (e.g. non-

Page 133 opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or inadequate to provide sufficient management of pain. Belbuca and Butrans^ are not indicated for as-needed (prn) analgesics.

Table 1. Maximum Recommended Dose Per Product Label Brand Active Ingredient Max Dose* Belbuca Buprenorphine (buccal film) 1800 mcg (900 mcg every 12 hours) Butrans^ Buprenorphine (patch) 20 mcg/hour patch every 7 days

*Doses are not considered equianalgesic and table does not represent a dose conversion chart.

4 . References

1. Belbuca [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.; July 2020. 2. Butrans [package insert]. Stamford, CT: Purdue Pharma L.P.; October 2019. 3. Franklin GM. Opioids for chronic noncancer pain. A position paper of the American Academy of Neurology. Neurology. 2014;83:1277-1284. 4. Rosenquist EWK. Overview of the treatment of chronic non-cancer pain in adults. Tauben, D. UptoDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed October 5, 2020). 5. Argoff CE, Silvershein DI. A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain: Tailoring Therapy to Meet Patient Needs. Mayo Clin Proc. 2009;84(7):602-612. 6. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. JAMA. Published online March 15, 2016.

5 . Revision History

Date Notes

12/11/2020 Added duration of trial requirement. Updated references.

Page 134 Benznidazole

Prior Authorization Guideline

GL-84704 Benznidazole

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 3/21/2018 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Indications Drug Name: Benznidazole Chagas disease (American trypanosomiasis) Indicated in pediatric patients 2 to 12 years of age for the treatment of Chagas disease (American trypanosomiasis), caused by Trypanosoma cruzi. [1]

2 . Criteria

Product Name: Benznidazole Diagnosis Chagas disease (American trypanosomiasis) Approval Length 60 Day(s) Guideline Type Notification

Page 135

Approval Criteria

1 - Diagnosis of Chagas disease (American trypanosomiasis) due to Trypanosoma cruzi

3 . Background

Benefit/Coverage/Program Information

Background

Benznidazole, a nitroimidazole antimicrobial, is indicated in pediatric patients 2 to 12 years of age for the treatment of Chagas disease (American trypanosomiasis), caused by Trypanosoma cruzi.1

Antiparasitic treatment is indicated for all cases of acute or reactivated Chagas disease and for chronic Trypanosoma cruzi (T. cruzi) infection in children up to 18 years old. Congenital infections are considered acute disease. Treatment is strongly recommended for adults up to 50 years old with chronic infection who do not already have advanced Chagas cardiomyopathy. For adults older than 50 years with chronic T. cruzi infection, the decision to treat with antiparasitic drugs should be individualized, weighing the potential benefits and risks for the patient. Physicians should consider factors such as the patient’s age, clinical status, preference, and overall health. 2

Additional clinical Rules • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Benznidazole [package insert]. Florham Park, NJ: Exeltis USA, Inc.: November 2019. 2. CDC Guidelines. Parasites – American Trypanosomiasis (also known as Chagas Disease). https://www.cdc.gov/parasites/chagas/. Accessed January 2021.

5 . Revision History

Page 136 Date Notes

4/30/2021 Annual review. No changes.

Page 137 Blood Glucose Test Strips

Prior Authorization Guideline

GL-87126 Blood Glucose Test Strips

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 4/18/2018 P&T Revision Date: 03/18/2020 ; 07/15/2020 ; 10/21/2020 ; 02/19/2021 ; 3/17/2021

1 . Criteria

Product Name: Abbott Diabetic Test Strips [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 All of the following:

• Patient is currently using an OmniPod Insulin Pump

Page 138 • Patient is requesting only FreeStyle test strips • Patient is not requesting FreeStyle Insulinx, FreeStyle Lite, FreeStyle Precision Neo or Precision Xtra test trips

1.2 All of the following:

• Patient is currently using a FreeStyle Libre Flash Glucose Monitoring System • Patient is requesting only FreeStyle Precision Neo test strips • Patient is not requesting FreeStyle, FreeStyle Insulinx, FreeStyle Lite, or Precision Xtra

1.3 Submission of medical records documenting a physical or mental limitation that makes utilization of one of the following meter/test strip products unsafe, inaccurate, or otherwise not feasible (e.g. manual dexterity)

• OneTouch UltraMini Meter (OneTouch Ultra Test Strips) • OneTouch Ultra 2 Meter (OneTouch Ultra Test Strips) • OneTouch Verio Meter (OneTouch Verio Test Strips) • OneTouch Verio IQ Meter (OneTouch Verio Test Strips) • OneTouch Verio Sync Meter (OneTouch Verio Test Strips) • Contour Next Meter (Contour Next Test Strips) • Contour Next One Meter (Contour Next Test Strips) • Contour Next EZ Meter (Contour Next Test Strips)

Product Name: Ascensia Diabetic Test Strips (excluding Contour Next**) [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Submission of medical records documenting a physical or mental limitation that makes utilization of one of the following diabetic meter/test strip products unsafe, inaccurate or otherwise not feasible (e.g., manual dexterity):

Page 139 • OneTouch UltraMini Meter (OneTouch Ultra Test Strips) • OneTouch Ultra 2 Meter (OneTouch Ultra Test Strips) • OneTouch Verio Meter (OneTouch Verio Test Strips) • OneTouch Verio IQ Meter (OneTouch Verio Test Strips) • OneTouch Verio Sync Meter (OneTouch Verio Test Strips) • Contour Next Meter (Contour Next Test Strips) • Contour Next One Meter (Contour Next Test Strips) • Contour Next EZ Meter (Contour Next Test Strips)

Notes **Contour Next test strips are covered without prior authorization revie w. [a] State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact covera ge criteria. Other policies and utilization management programs may a pply.

Product Name: Roche Diabetic Test Strips (excluding Accu-Chek Guide**) [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 All of the following:

• Patient is currently utilizing an Accu-Chek Combo Insulin Pump • Patient is requesting only Accu-Chek Aviva Plus test strips • Patient is not requesting Accu-Chek Compact, Accu-Chek Compact Plus, or Accu-Chek Smartview test strips

1.2 Submission of medical records documenting a physical or mental limitation that makes utilization of one of the following diabetic meters/test strips product unsafe, inaccurate or otherwise not feasible (e.g. manual dexterity):

Page 140 • Contour Next One Meter (Contour Next Test Strips) • Contour Next EZ Meter (Contour Next Test Strips)

Product Name: Other non-preferred test strip products (excluding Accu-Chek Guide, and Contour Next**) [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Submission of medical records documenting a physical or mental limitation that makes utilization of one of the following diabetic meter/test trip products unsafe, inaccurate, or otherwise not feasible (e.g. manual dexterity)

1.2 Patient is currently on an insulin pump that requires a specific glucometer/test strip Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Preferred or non-preferred test strip products [a] Approval Length 12 month(s)

Page 141 Guideline Type Quantity Limit

Approval Criteria

1 - Physician confirmation that the patient requires a greater quantity because of more frequent blood glucose testing (e.g., patients on intravenous insulin infusions)* Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Self-monitoring of blood-glucose should be carried out three or mor e times daily for patients using multiple insulin injections or insulin pum p therapy. For patients using less frequent insulin injections, non-insuli n therapies, or medical nutrition therapy alone, self-monitoring of blood glucose may be useful as a guide to management. [1]

2 . Background

Benefit/Coverage/Program Information

Background:

The American Diabetes Association (ADA) recommends routine blood glucose monitoring in patients using insulin therapy. The ADA also notes that blood glucose monitoring may be helpful to guide treatment decisions for patients using noninsulin therapies. The ADA does not differentiate between brands of diabetic meters or test strips in their recommendation.

This program allows members utilizing an insulin pump to continue on their current diabetic meter/test strip if it the diabetic meter/strip is part of the system and interfaces directly with the insulin pump. Members not utilizing an insulin pump must have documentation demonstrating why utilization of a OneTouch or Contour Next diabetic meter/test strip is unsafe, inaccurate or not feasible before coverage will be provided for Abbott, Ascensia, or Roche diabetic test strips.

Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • ** Accu-Chek Guide test strips and Contour Next test strips are covered without prior authorization review.

Page 142 3 . References

1. American Diabetes Association; Standards of Medical Care in Diabetes – 2020. Diabetes Care 2020: Jan; 43 (Supplement 1): S1-S212

4 . Revision History

Date Notes

5/18/2021 03/2021 P&T - Removed Accu-Chek Guide from the criteria. Accu-Che k Guide test strips and meters will be covered without prior authorizatio n review.

Page 143 Bonjesta (doxylamine/pyridoxine extended-release), Diclegis (doxylamine/pyridoxine delayed release) - PA/Med Nec

Prior Authorization Guideline

GL-76738 Bonjesta (doxylamine/pyridoxine extended-release), Diclegis (doxylamine/pyridoxine delayed release) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 4/18/2014 P&T Revision Date: 09/18/2019 ; 10/21/2020

1 . Indications Drug Name: Bonjesta (doxylamine/pyridoxine extended-release), Diclegis (doxylamine/pyridoxine delayed release) Nausea and vomiting of pregnancy Approved by the Food and Drug Administration (FDA) for the treatment of nausea and vomiting of pregnancy in women who have not responded to conservative management.

2 . Criteria

Product Name: Bonjesta* or Diclegis* [a] Approval Length 9 month(s)

Page 144 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of nausea and vomiting associated with pregnancy

AND

2 - Documented failure or contraindication to lifestyle modifications (e.g., diet, avoidance of triggers)

AND

3 - Documented trial and failure or contraindication to a five day trial of over-the-counter doxylamine taken together with pyridoxine (i.e., not a combined dosage form, but separate formulations taken concomitantly) Notes *Bonjesta and Diclegis (as of 1/1/2019) are typically excluded from cov erage. [a] State mandates may apply. Any federal regulatory requireme nts and the member specific benefit plan coverage may also impact co verage criteria. Other policies and utilization management programs m ay apply.

3 . Background

Benefit/Coverage/Program Information

Background:

Bonjesta and Diclegis are fixed dose combinations of doxylamine and pyridoxine approved by the Food and Drug Administration (FDA) for the treatment of nausea and vomiting of pregnancy in women who have not responded to conservative management.

Additional Clinical Rules:

Bonjesta and Diclegis (as of 1/1/2019) are typically excluded from coverage.

• Supply limitations may be in place.

Page 145 • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Diclegis [package insert]. Bryn Mawr, PA: Duchesnay USA, Inc.; June 2018. 2. "ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: Nausea and vomiting of pregnancy." Obstetrics and gynecology 2018; 131(1) e15-e30. 3. Herrell HE. Nausea and vomiting of pregnancy. Am Fam Physician 2014 Jun 15;89(12):965-970. 4. Bonjesta [package insert]. Bryn Mawr, PA: Duchesnay USA, Inc.; June 2018.

5 . Revision History

Date Notes

11/10/2020 Annual review. Updated reference, clarified Diclegis dosage form.

Page 146 BPH Agents

Prior Authorization Guideline

GL-80424 BPH Agents

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 5/22/1998 P&T Revision Date: 02/13/2020 ; 2/18/2021

1 . Indications Drug Name: Cardura XL (doxazosin mesylate extended-release) Benign prostatic hyperplasia (BPH) Indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Cardura XL is NOT indicated for the treatment of hypertension.

2 . Criteria

Product Name: Cardura XL Approval Length 12 month(s) Guideline Type Step Therapy

Page 147

Approval Criteria

1 - Trial and failure, contraindication, or intolerance to any TWO of the following generics: [2]

• alfuzosin • doxazosin • tamsulosin • terazosin • silodosin

3 . References

1. Cardura XL prescribing information. Pfizer, Inc. New York, New York. January 2019. 2. The American Urological Association. Management of benign prostatic hyperplasia. Available at: http://www.auanet.org/benign-prostatic-hyperplasia-(2010-reviewed-and- validity-confirmed-2014). Accessed February 1, 2021.

4 . Revision History

Date Notes

2/3/2021 Annual review - background and reference updates

Page 148 Breast Cancer Prevention Zero Dollar Cost Share - generic tamoxifen (applies to 20mg dose only) and generic raloxifene, generic aromatase inhibitors (anastrozole, letrozole, or exemestane)

Prior Authorization Guideline

GL-71966 Breast Cancer Prevention Zero Dollar Cost Share - generic tamoxifen (applies to 20mg dose only) and generic raloxifene, generic aromatase inhibitors (anastrozole, letrozole, or exemestane)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/8/2014 P&T Revision Date: 12/18/2019 ; 7/15/2020

1 . Criteria

Product Name: Tamoxifen (20 mg dose only), generic raloxifene, generic anastrozole, generic letrozole, or generic exemestane Diagnosis Breast Cancer Prevention Zero Dollar Cost Share Approval Length 60 month(s) Guideline Type Notification

Approval Criteria

Page 149

1 - Coverage at zero dollar cost share will be approved based on all of the following criteria:

1.1 Member is greater than or equal to 35 years of age [a]

AND

1.2 Member does not have a prior diagnosis of any of the following:

• breast cancer • ductal carcinoma in situ (DCIS) • lobular carcinoma in situ (LCIS)

AND

1.3 Member does not have a history of thromboembolic events (e.g., deep venous thrombosis, pulmonary embolus, stroke or transient ischemic attack)

AND

1.4 Member has an estimated 5 year risk of breast cancer based on a breast cancer risk assessment tool of greater than or equal to 3%. [2]

AND

1.5 One of the following:

1.5.1 Request is for generic tamoxifen 20mg once daily

1.5.2 Both of the following:

1.5.2.1 Member is post-menopausal

AND

Page 150 1.5.2.2 One of the following:

• Request is for generic raloxifene 60 mg once daily • Request is for generic anastrozole • Request is for generic letrozole • Request is for generic exemestane, and member has had failure, contraindication or adverse reaction to anastrozole or letrozole

Notes Authorization will be issued for zero copay with deductible bypass for u p to a total of 60 months (please determine if member has already rece ived some length of therapy and if so subtract from total approval perio d). [a] Not applicable to plans sitused in District of Columbia

2 . Background

Benefit/Coverage/Program Information

Background: The U.S. Preventive Services Task Force (USPSTF)1 recommends that clinicians engage in shared, informed decision making with women who are at increased risk for breast cancer about medications to reduce their risk. For women who are at increased risk of breast cancer and at low risk of adverse medication effects, clinicians should offer to prescribe risk-reducing medications.

This program is designed to meet Health Care Reform requirements which require coverage of tamoxifen tablets, raloxifene or aromatase inhibitors [anastrozole (generic Arimidex), letrozole (generic Femara), or exemestane (generic Aromasin)] at zero dollar cost share if being used for primary prevention of breast cancer and criteria are met. Additional Clinical Rules:

3 . References

1. U.S. Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/ Accessed 5/2019

Page 151 2. Assessment of Breast Cancer Risk Status. U.S. Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/uspstf13/breastcanmeds/breastcanmedsrs .htm Accessed 5/2019

4 . Revision History

Date Notes

8/27/2020 Added coverage of Aromatase Inhibitors as in scope.

Page 152 Bronchitol (mannitol)

Prior Authorization Guideline

GL-90236 Bronchitol (mannitol)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/17/2021 P&T Approval Date: 6/16/2021

P&T Revision Date:

1 . Indications Drug Name: Bronchitol (mannitol) Cystic Fibrosis Indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years of age and older with cystic fibrosis.

2 . Criteria

Product Name: Bronchitol [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 153

Approval Criteria

1 - Diagnosis of cystic fibrosis

AND

2 - Used in conjunction with standard CF therapies [e.g., chest physiotherapy, bronchodilators, antibiotics, anti-inflammatory therapy (e.g., ibuprofen, oral/inhaled corticosteroids)]

AND

3 - Patient has passed the Bronchitol Tolerance Test

AND

4 - History of failure, contraindication, or intolerance to inhaled hypertonic saline (e.g., Hyper- Sal) (document date of trial and list reason for therapeutic failure, contraindications, or intolerance) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Bronchitol [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Bronchitol therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 154

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Programs:

Background

Bronchitol is a sugar alcohol indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years of age and older with cystic fibrosis. Use Bronchitol only in adults who have passed the Bronchitol Tolerance Test.

This program requires a member to try hypertonic saline before providing coverage for Bronchitol.

4 . References

1. Bronchitol [package insert]. Cary, NC: Chiesi USA, Inc.; October 2020.

5 . Revision History

Date Notes

7/21/2021 6/2021 P&T - New program.

Page 155 Caduet (amlodipine/atorvastatin)

Prior Authorization Guideline

GL-13198 Caduet (amlodipine/atorvastatin)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 2/19/2013; CPS Revision Date: 7/14/2015

1 . Indications Drug Name: Caduet (amlodipine/atorvastatin) General Indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate. Limitations of use: The antidyslipidemic component of Caduet has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).

Drug Name: Amlodipine Hypertension Indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents

Coronary Artery Disease (CAD) - Chronic Stable Angina Indicated for the treatment of

Page 156 chronic stable angina. Amlodipine may be used alone or in combination with other antianginal or antihypertensive agents

CAD - Vasospastic Angina (Prinzmetal’s or Variant Angina) Indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine may be used as monotherapy or in combination with other antianginal drugs.

Angiographically Documented CAD In patients with recently documented CAD by angiography and without heart failure or an ejection fraction < 40%, amlodipine is indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure.

Drug Name: Atorvastatin General Therapy with HMG CoA-reductase inhibitors (lipid-altering agents) should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease from hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with CHD or multiple risk factors for CHD, atorvastatin can be started simultaneously with diet restriction.

Prevention of Cardiovascular Disease In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C, or a family history of early coronary heart disease, atorvastatin is indicated to: • Reduce the risk of myocardial infarction • Reduce the risk of stroke • Reduce the risk for revascularization procedures and angina In patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, atorvastatin is indicated to: • Reduce the risk of myocardial infarction • Reduce the risk of stroke In patients with clinically evident coronary heart disease, atorvastatin is indicated to: • Reduce the risk of non-fatal myocardial infarction • Reduce the risk of fatal and non-fatal stroke • Reduce the risk for revascularization procedures • Reduce the risk of hospitalization for CHF • Reduce the risk of angina

Hyperlipidemia Indicated: • As an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb) • As an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson Type IV); • For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who do not respond adequately to diet • To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable • As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: 1. LDL-C remains greater than or equal to 190 mg/dL or 2. LDL- C remains greater than or equal to 160 mg/dL and: • there is a positive family history of premature cardiovascular disease or • two or more other CVD risk factors are present in the pediatric patient

Page 157

2 . Criteria

Product Name: Brand Caduet or Generic amlodipine/atorvastatin Guideline Type Step Therapy

Approval Criteria

1 - History of amlodipine

AND

2 - History of one of the following:

• One formulary statin (eg, lovastatin, simvastatin, pravastatin, atorvastatin, or Crestor) • Vytorin

3 . References

1. Caduet Prescribing Information. Pfizer. March 2015. 2. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106:3143. 3. Grundy SM, Cleeman JI, Bairey Merz CN, et al. The Adult Treatment Panel (ATP) III Update 2004: Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 2004; 110:227-239.

Page 158 Caplyta (lumateperone) - PA/Med Nec

Prior Authorization Guideline

GL-69288 Caplyta (lumateperone) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2020 P&T Approval Date: 6/17/2020

P&T Revision Date:

1 . Indications Drug Name: Caplyta Schizophrenia Indicated for the treatment of schizophrenia in adults.

2 . Criteria

Product Name: Caplyta [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 159 Approval Criteria

1 - Documentation of BOTH of the following:

1.1 Diagnosis of schizophrenia

AND

1.2 History of failure, contraindication, or intolerance to three of the following (please document drug, date and duration of trial):

• aripiprazole (generic Abilify) • olanzapine (generic Zyprexa) • quetiapine IR or ER (generic Seroquel IR or XR) • risperidone (generic Risperdal) • ziprasidone (generic Geodon)

2 - Treatment with Caplyta was initiated at a recent behavioral inpatient admission (discharge within the past 3 months) and the member is currently stable on therapy. (Please document date of discharge from inpatient admission). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Caplyta [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of a positive clinical response to therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 160

3 . Background

Benefit/Coverage/Program Information

Background: Caplyta is FDA approved for the treatment of schizophrenia in adults. This program requires a member to try three atypical antipsychotics before providing coverage for Caplyta. Additional Clinical Programs:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits and Prior Authorization/Notification may also be in place.

4 . References

1. Caplyta [prescribing information]. New York, NY: Intra-Cellular Therapies, Inc. December 2019. 2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia Second Edition. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizop hrenia.pdf

5 . Revision History

Date Notes

7/15/2020 New program.

Page 161 Cetraxal (ciprofloxacin otic suspension)

Prior Authorization Guideline

GL-45234 Cetraxal (ciprofloxacin otic suspension)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 5/21/1999; P&T Revision Date: 11/18/2015, 12/20/2017, 11/15/2018. **Effective Date: 1/1/2019**

1 . Indications Drug Name: Cetraxal (ciprofloxacin otic solution) Acute otitis externa Indicated for the treatment of acute otitis externa due to susceptible isolates of Pseudomonas aeruginosa or Staphylococcus aureus.

2 . Criteria

Product Name: Brand Cetraxal, Generic ciprofloxacin otic solution

Page 162 Approval Length 12 Months Guideline Type Step Therapy

Approval Criteria

1 - Trial and failure, contraindication, or intolerance to ofloxacin otic solution

3 . References

1. Jones RN, Milazzo J, Seidlin M. Ofloxacin otic solution for treatment of otitis externa in children and adults. Arch Otolaryngol Head Neck Surg 1997;123:1193-200. 2. Cetraxal Prescribing Information. Wraser Pharmaceuticals. Columbia, SC. December 2017. 3. Rosenfeld RM, Schwartz SR, Cannon CR, et al. Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg. 2014;150(1):S1-S24.

Page 163 CGRP Antagonists - PA/Med Nec

Prior Authorization Guideline

GL-71280 CGRP Antagonists - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2020 P&T Approval Date: 6/20/2018 P&T Revision Date: 07/17/2019 ; 7/15/2020

1 . Indications Drug Name: Aimovig, Ajovy*, and Emgality 120mg Migraine Indicated for the preventive treatment of migraine in adults.

Drug Name: Emgality 100mg Episodic Cluster Headache Indicated for the treatment of episodic cluster headache in adults.

2 . Criteria

Product Name: Aimovig or Emgality 120mg [a] Diagnosis Episodic Migraines Approval Length 6 month(s)

Page 164 Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of episodic migraines with both of the following:

• Less than 15 headache days per month • Patient has 4 to 14 migraine days per month

AND

2 - Trial and failure (after a trial of at least two months [b]), contraindication, or intolerance to two of the following prophylactic therapies from the list below (document name and date tried):

• Amitriptyline (Elavil) • One of the following beta-blockers: atenolol, metoprolol, nadolol, propranolol, or timolol • Divalproex sodium (Depakote/Depakote ER) • Topiramate (Topamax) • Venlafaxine (Effexor/Effexor XR)

AND

3 - Medication will not be used in combination with another biologic CGRP antagonist or inhibitor [e.g., Ajovy, Vyepti (eptinezumab-jjmr)] Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required.

Product Name: Ajovy* [a] Diagnosis Episodic Migraines Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

Page 165

1 - Diagnosis of episodic migraines with both of the following:

• Less than 15 headache days per month • Patient has 4 to 14 migraine days per month

AND

2 - Trial and failure (after a trial of at least two months [b]), contraindication, or intolerance to two of the following prophylactic therapies from the list below (document name and date tried):

AND

3 - Trial and failure (after a trial of at least three months [b]), contraindication, or intolerance to both of the following (document date tried):

• Aimovig • Emgality 120mg

AND

4 - Medication will not be used in combination with another biologic CGRP antagonist or inhibitor (e.g., Aimovig, Emgality, Vyepti) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required. * Ajovy is typically excluded from benefit coverage.

Product Name: Aimovig, Ajovy* or Emgality 120mg [a] Diagnosis Episodic Migraines Approval Length 12 month(s) Therapy Stage Reauthorization

Page 166 Guideline Type Prior Authorization

Approval Criteria

1 - Patient has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity

AND

2 - Medication will not be used in combination with another biologic CGRP antagonist or inhibitor (e.g., Vyepti) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Ajovy is typically excluded from benefit coverage

Product Name: Aimovig or Emgality 120mg [a] Diagnosis Chronic Migraines Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of chronic migraines with both of the following:

• Greater than or equal to 15 headache days per month • Greater than or equal to 8 migraine days per month

AND

2 - Trial and failure (after a trial of at least two months [b]), contraindication, or intolerance to two of the following prophylactic therapies from the list below (document name and date tried):

• Amitriptyline (Elavil) • One of the following beta-blockers: atenolol, metoprolol, nadolol, propranolol, or timolol • Divalproex sodium (Depakote/Depakote ER) • OnabotulinumtoxinA (Botox)

Page 167 • Topiramate (Topamax) • Venlafaxine (Effexor/Effexor XR)

AND

3 - Medication will not be used in combination with another biologic CGRP antagonist or inhibitor (e.g., Ajovy, Vyepti) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required.

Product Name: Ajovy* [a] Diagnosis Chronic Migraines Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of chronic migraines with both of the following:

• Greater than or equal to 15 headache days per month • Greater than or equal to 8 migraine days per month

AND

2 - Trial and failure (after a trial of at least two months [b]), contraindication, or intolerance to two of the following prophylactic therapies from the list below (document name and date tried):

• Amitriptyline (Elavil) • One of the following beta-blockers: atenolol, metoprolol, nadolol, propranolol, or timolol • Divalproex sodium (Depakote/Depakote ER) • OnabotulinumtoxinA (Botox) • Topiramate (Topamax) • Venlafaxine (Effexor/Effexor XR)

Page 168 AND

3 - Trial and failure (after a trial of at least three months [b]), contraindication, or intolerance to both of the following (document date tried):

• Aimovig • Emgality 120mg

AND

Product Name: Aimovig, Ajovy* or Emgality 120mg [a] Diagnosis Chronic Migraines Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity

AND

Page 169 Product Name: Emgality 100mg [a] Diagnosis Episodic Cluster Headache Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of episodic cluster headache

AND

2 - Patient has experienced at least 2 cluster periods lasting from 7 days to 365 days, separated by pain-free periods lasting at least three months

AND

3 - Medication will not be used in combination with another biologic CGRP antagonist or inhibitor (e.g., Aiovig, Ajovy, Vyepti). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Emgality 100mg [a] Diagnosis Episodic Cluster Headache Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity

Page 170 AND

2 - Medication will not be used in combination with another biologic CGRP antagonist or inhibitor (e.g., Aimovig, Ajovy, Vyepti) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

4 . References

1. Aimovig [package insert]. Thousand Oaks, CA: Amgen Inc; April 2020. 2. Ajovy [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc; February 2020. 3. Emgality [package insert]. Indianapolis, IN: Eli Lilly and Company. December 2019. 4. International Headache Society (IHS); Headache Classification Committee. The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018; 38:1- 211. 5. The American Headache Society Position Statement on Integrating New Migraine Treatments into Clinical Practice. Headache: The Journal of Head and Face Pain. 2019;59: 1-18. 6. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012 Apr 24;78(17):1337-45. 7. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May 10;86(19):1818-26.

Page 171

5 . Revision History

Date Notes

8/11/2020 Annual review. Updated initial authorization duration. Added document ation requirement. Modified concomitant CGRP use to allow non-biolo gic CGRPs.

Page 172 CNS Stimulants

Prior Authorization Guideline

GL-90174 CNS Stimulants

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 9/27/2017 P&T Revision Date: 07/17/2019 ; 08/16/2019 ; 10/16/2019 ; 03/18/2020 ; 08/14/2020 ; 02/19/2021 ; 5/21/2021

1 . Criteria

Product Name: Brand Adderall, Adhansia XR, Adzenys ER, Adzenys XR-ODT, Aptensio XR, Cotempla XR-ODT, Daytrana, brand Dexedrine, brand Dexedrine Spansule, Dyanavel XR, Evekeo, Evekeo ODT, brand Focalin XR, Jornay PM, brand Metadate CD, Metadate ER, Methylin, Methylin ER, methylphenidate ER 72mg, Mydayis, Procentra, QuilliChew ER, Quillivant XR, Ritalin SR, brand Ritalin LA, and brand Zenzedi Approval Length 12 month(s) Guideline Type Non-Formulary or Step Therapy

Approval Criteria

Page 173 1 - History of two of the following generics or preferred brands:

• amphetamine-dextroamphetamine IR • dexmethylphenidate IR • dextroamphetamine IR or SR • methylphenidate IR (generic Ritalin) or methylphenidate ER (generic Metadate CD, Ritalin LA) • brand Adderall XR • brand Concerta

Product Name: Generic amphetamine-dextroamphetamine mixed salts extended-release (generic Adderall XR) or methylphenidate ER (generic Concerta) Approval Length 12 month(s) Guideline Type Non Formulary

Approval Criteria

1 - One of the following:

1.1 If the request is for generic amphetamine-dextroamphetamine mixed salts extended- release (generic Adderall XR), the patient has a history of failure or intolerance to brand Adderall XR

1.2 If the request is for generic methylphenidate ER (generic Concerta), the patient has a history of failure or intolerance to brand Concerta

2 . Background

Benefit/Coverage/Program Information

Background:

Step therapy programs are utilized to encourage use of lower cost alternatives for certain therapeutic classes. This program requires a member to try brand Adderall XR before providing coverage for generic amphetamine-dextroamphetamine mixed salts extended-release (generic Adderall XR), brand Concerta before providing coverage for generic methylphenidate ER

Page 174 (generic Concerta), and two generic or preferred brand CNS alternatives before providing coverage for other non-preferred medications.

Additional Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic.Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply Limits may also be in place.

3 . References

1. Adderall [package insert]. Parsippany, NJ: Teva Pharmaceuticals; March 2020. 2. Adderall XR [package insert]. Lexington, MA: Shire US Inc; July 2019. 3. Focalin [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2019. 4. Focalin XR [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2019. 5. Daytrana [package insert]. Miami, FL: Noven Therapeutics, LLC;. November 2017. 6. Dexedrine Spansule sustained-release capsules [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals; March 2019. 7. Desoxyn [package insert]. Lebanon, NJ: Recordati Rare Diseases Inc; March 2019. 8. ProCentra [package insert]. Newport, KY: Independence Pharmaceuticals; February 2017. 9. Ritalin/Ritalin SR [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; November 2019. 10. Ritalin LA [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; November 2019. 11. Metadate CD [package insert]. Smyrna, GA. UCB Manufacturing, Inc. October 2016. 12. Metadate ER [package insert]. Smyrna, GA: UCB, Inc; April 2018. 13. Concerta [package insert]. Titusville, NJ. Janssen Pharmaceuticals. January 2017. 14. Methylin chewable tablets [package insert]. Florham Park, NJ: Shionogi Inc; February 2015. 15. Methylin oral solution [package insert]. Florham Park, NJ: Shionogi Inc; August 2017. 16. Aptensio XR [package insert]. Coventry, RI. Rhodes Pharmaceuticals L.P. October 2016. 17. QuilliChew ER extended-release chewable tablets [package insert]. New York, NY: Pfizer; August 2018. 18. Dyanavel XR [package insert]. Monmouth Junction, NJ. Tris Pharma, Inc. February 2019. 19. Adzenys XR-ODT [package insert]. Grand Prairie, TX: Neos Therapeutics; February 2018. 20. Adzenys ER [package insert]. Grand Prairie, TX: Neos Therapeutics; September 2017. 21. Quillivant XR [package insert]. New York, NY: Pfizer Inc; August 2018. 22. Cotempla XR-ODT [package insert]. Grand Prairie, TX: Neos Therapeutics Brands, LLC; June 2017. 23. Mydayis [package insert]. Lexington, MA: Shire US Inc; September 2019. 24. Jornay PM [package insert]. Cherry Hill, NJ: Ironshore Pharmaceuticals, Inc; April 2019.

Page 175 25. Adhansia XR extended-release capsules [package insert]. Wilson, NC: Purdue Pharmaceuticals; July 2019. 26. Evekeo ODT [package insert]. Atlanta, GA: Arbor Pharmaceuticals LLC; March 2019. 27. Zenzedi [package insert]. Atlanta, GA: Arbor Pharmaceuticals LLC; February 2017.

4 . Revision History

Date Notes

7/21/2021 5/2021 P&T - Removed Desoxyn, brand Focalin and brand Ritalin from criteria. Added methylphenidate ER 72mg to criteria. Administrative up date to add Adhansia XR and Evekeo ODT back in to criteria. Clarified preferred methylphenidate IR and ER products. Updated references.

Page 176 Colchicine Tablet (Colcrys authorized generic)

Prior Authorization Guideline

GL-88417 Colchicine Tablet (Colcrys authorized generic)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 5/20/2016 P&T Revision Date: 05/15/2020 ; 05/15/2020 ; 5/21/2021

1 . Indications Drug Name: Colcrys (colchicine tablet) Familial Mediterranean fever (FMF) Indicated for the treatment of familial Mediterranean fever (FMF).

Prophylaxis of Gout Indicated for prophylaxis and the treatment of gout flares.

Drug Name: Gloperba (colchicine oral solution), Mitigare (colchicine capsule) Gout Indicated for the prophylaxis of acute gout flares.

2 . Criteria

Product Name: Colchicine tablet (generic Colcrys)*

Page 177 Approval Length 12 month(s) Guideline Type Notification

Approval Criteria

1 - Patient requires a reduced dose of 0.3 mg (half of a 0.6 mg tablet) due to one of the following criteria:

• Severe renal impairment (e.g. estimated creatinine clearance less than 30 mL/min) • Severe hepatic impairment (e.g. Child-Pugh score of B or C) • Concomitant use of a CYP3A4 inhibitor (e.g. clarithromycin, itraconazole), P- glycoprotein inhibitor (e.g. cyclosporine), or a protease inhibitor (e.g. Reyataz) • The treatment of familial Mediterranean fever • Intolerable side effects that cannot be managed by extending the dosing interval

Notes *Colcrys, colchicine tablets, and colchicine capsules are typically exclu ded from coverage

3 . Background

Benefit/Coverage/Program Information

Background

Gloperba (colchicine oral solution) and Mitigare (colchicine capsule)* are indicated for the prophylaxis of acute gout flares. Colcrys (colchicine tablet)* is indicated for prophylaxis and the treatment of gout flares and the treatment of familial Mediterranean fever (FMF). The recommended dose for the prophylaxis of gout flares is 0.6 mg once to twice daily up to a maximum dose of 1.2 mg per day. Patients with severe renal or hepatic impairment and patients taking concomitant CYP3A4 inhibitors, P-glycoprotein inhibitors, or protease inhibitors may require a reduced dose of 0.3 mg per day. The recommended dose for the treatment of gout flares is 1.2 mg followed by 0.6 mg one hour later. For FMF, the recommended dose is 1.2 to 2.4 mg daily, titrated by 0.3 mg increments to manage side effects.

Additional Clinical Rules • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

Page 178 1. Colcrys [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; May 2020. 2. Gloperba [package insert]. Alpharetta, GA: Avion Pharmaceuticals, LLC; February 2019. 3. Mitigare [package insert]. Memphis, TN: Hikma Americas, Inc.; June 2020.

5 . Revision History

Date Notes

6/15/2021 Annual review. Updated background section and references.

Page 179 Compounds and Bulk Powders

Prior Authorization Guideline

GL-80507 Compounds and Bulk Powders

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 1/18/2012 P&T Revision Date: 10/16/2019 ; 05/15/2020 ; 1/20/2021

1 . Criteria

Product Name: Compounds and bulk powders^ [a] Approval Length 12 month(s) Guideline Type Notification

Approval Criteria

1 - The requested drug component is a covered medication

AND

Page 180

2 - The requested drug component is to be administered for an FDA-approved indication

AND

3 - If a drug included in the compound requires prior authorization and/or step therapy, all drug specific clinical criteria must also be met

AND

4 - If the drug component is no longer available commercially it must not have been withdrawn for safety reasons

AND

5 - One of the following:

5.1 A unique vehicle is required for topically administered compounds

5.2 A unique dosage form is required for a commercially available product due to patient's age, weight or inability to take a solid dosage form.

5.3 A unique formulation is required for a commercially available product due to an allergy or intolerance to an inactive ingredient in the commercially available product

5.4 There is a shortage of the commercially available product per the FDA Drug Shortage database or the ASHP Current Drug Shortages tracking log

AND

Page 181

6 - Coverage for compounds and bulk powders will NOT be approved for any of the following:

6.1 Requested compound contains any of the following ingredients which are available as over-the-counter products:

• Cetyl Myristoleate • Coenzyme Q10 • Methylcobalamin • Hyaluronic Acid • Nicotinamide • Methyltetrahydrofolate • Ibuprofen • Lipoic acid • Beta Glucan • Ubiquinol • Chrysin • Glutathione • Lactobacillus • Vitamin E • Ascorbic Acid • Melatonin • Pyridoxal-5-Phosphate (Vitamin B6) • Loperamide • Dextromethorphan • Dehydroepiandrosterone • Pregnenolone • Biotin • L-Glutamine • Serotonin • Aloe vera • Sodium butyrate • L-Isoleucine • Vitamin D3 • Ginseng • Phosphatidylserine • Resveratrol • Methionine • Naproxen • Carnosine L • Arnica LG

6.2 For topical compound preparations (e.g., creams, ointments, lotions or gels to be applied to the skin for transdermal, transcutaneous or any other topical route), requested compound contains any FDA approved ingredient that is not FDA approved for TOPICAL use, including but NOT LIMITED TO the following:

Page 182 • Ketamine • Gabapentin • Flurbiprofen (topical ophthalmic use not included) • Ketoprofen • Morphine • Nabumetone • Oxycodone • Cyclobenzaprine • Baclofen • Tramadol • Hydrocodone • Meloxicam • Amitriptyline • Pentoxifylline • Orphenadrine • Piroxicam • Levocetirizine • Amantadine • Oxytocin • Sumatriptan • Chorionic gonadotropin (human) • Clomipramine • Dexamethasone • Hydromorphone • Methadone • Papaverine • Mefenamic acid • Promethazine • Succimer DMSA • Tizanidine • Apomorphine • Carbamazepine • Ketorolac • Dimercaptopropane-sulfonate • Dimercaptosuccinic acid • Duloxetine • Fluoxetine • Bromfenac (topical ophthalmic use not included) • Nepafenac (topical ophthalmic use not included)

6.3 Requested compound contains topical fluticasone. Topical fluticasone will NOT be approved unless:

6.3.1 Topical fluticasone is intended to treat a dermatologic condition. Scar treatments are considered cosmetic and will not be covered (refer to criteria "6.5" below).

Page 183

AND

6.3.2 Patient has a contraindication to all commercially available topical fluticasone formulations

6.4 Requested compound contains leuprolide when prescribed for off-label use (refer to leuprolide criteria)

6.5 Requested compound is for cosmetic use or contains any of the following ingredients when used for cosmetic purposes:

• Hydroquinone • Acetyl hexapeptide-8 • Tocopheryl Acid Succinate • PracaSil TM-Plus • Chrysaderm Day Cream • Chrysaderm Night Cream • PCCA Spira-Wash • Lipopen Ultra • Versapro • Fluticasone • Mometasone • Halobetasol • Betamethasone • Clobetasol • Triamcinolone • Minoxidil • Tretinoin • Dexamethasone • Spironolactone • Cycloserine • Tamoxifen • Sermorelin • Mederma Cream • PCCA Cosmetic HRT Base • Sanare Scar Therapy Cream • Scarcin Cream • Apothederm

Page 184 • Stera Cream • Copasil • Collagenase • Arbutin Alpha • Nourisil • Freedom Cepapro • Freedom Silomac Andydrous • Retinaldehyde • Apothederm

6.6 Requested compound contains cholestyramine when prescribed for off-label use. (FDA labeled uses include: hypercholesterolemia, coronary artery atherosclerosis, and pruritus associated with biliary obstruction)

6.7 Requested compound contains nystatin when prescribed for an off-label use

6.8 Requested compound contains any of the following ingredients which are on the FDA's Do Not Compound List:

• 3,3',4',5-tetrachlorosalicylanilide • Adenosine phosphate • Adrenal cortex • Alatrofloxacin mesylate • Aminopyrine • Astemizole • Azaribine • Benoxaprofen • Bithionol • Camphorated oil • Carbetapentane citrate • Casein, iodinated • Cerivastatin sodium • Chlormadinone acetate • Chloroform • Cisapride • Exfenfluramine hydrochloride • Diamthazole dihydrochloride

Page 185 • Dibromsalan • Dihydrostreptomycin sulfate • Dipyrone • Encainide hydrochloride • Etretinate • Fenfluramine hydrochloride • Flosequinan • Glycerol, iodinated • Grepafloxacin • Mepazine • Metabromsalan • Methapyrilene • Methopholine • Methoxyflurane • Mibefradil dihydrochloride • Nomifensine maleate • Novobiocin sodium • Oxyphenisatin acetate • Oxyphenisatin • Pemoline • Pergolide mesylate • Phenacetin • Phenformin hydrochloride • Phenylpropanolamine • Pipamazine • Potassium arsenite • Propoxyphene • Rapacuronium bromide • Rofecoxib • Sibutramine hydrochloride • Sparteine sulfate • Sulfadimethoxine • Sweet spirits of nitre • Tegaserod maleate • Temafloxacin hydrochloride • Terfenadine • Ticrynafen • Tribromsalan • Trichloroethane • Troglitazone • Trovafloxacin mesylate • Urethane • Valdecoxib • Zomepirac sodium

Notes ^Includes bulk powders requested as a single ingredient such as bulk p owder formulations of cholestyramine or nystatin when the powder for mulation requested is not the commercially available FDA approved pr oduct [a] For Kentucky, requests for therapeutic food, formulas, supple

Page 186 ments, low-protein modified food products, vitamins, nutritional supple ments and amino acid-based elemental medical formula for the treatm ent of inborn errors of metabolism, genetic conditions, mitochondrial di sease, food protein allergies, food protein-induced enterocolitis syndro me, eosinophilic disorders, or short-bowel syndrome may be approved through review by UnitedHealthcare Pharmacy. Please note there is a plan year cap of twenty five thousand dollars ($25,000) for therapeutic f oods, formulas and supplements, and a separate cap for each plan yea r of four thousand dollars ($4,000) on low-protein modified foods. Each cap shall be subject to annual inflation adjustments based on the cons umer price index.

Product Name: First-Lansoprazole, First-Omeprazole, and Omeprazole + Syrspend SF compounding kits [a] Approval Length 12 month(s) Guideline Type Notification

Approval Criteria

1 - The requested drug component in the compounding kit is to be administered for an FDA- approved indication

AND

2 - One of the following:

2.1 A unique dosage form is required for a covered commercially available product due to the patient' age, weight or inability to take a solid dosage form

2.2 A unique formulation is required for a covered commercially available product due to an allergy or intolerance to an inactive ingredient in the commercially available product Notes [a] For Kentucky, requests for therapeutic food, formulas, supplements, low-protein modified food products, vitamins, nutritional supplements a nd amino acid-based elemental medical formula for the treatment of in born errors of metabolism, genetic conditions, mitochondrial disease, f ood protein allergies, food protein-induced enterocolitis syndrome, eosi nophilic disorders, or short-bowel syndrome may be approved through review by UnitedHealthcare Pharmacy. Please note there is a plan yea r cap of twenty five thousand dollars ($25,000) for therapeutic foods, fo

Page 187 rmulas and supplements, and a separate cap for each plan year of four thousand dollars ($4,000) on low-protein modified foods. Each cap sh all be subject to annual inflation adjustments based on the consumer pr ice index.

2 . Background

Benefit/Coverage/Program Information

Background: Compounded medications can provide a unique route of delivery for certain patient- specific conditions and administration requirements. Compounded medications should be produced for a single individual and not produced on a large scale. A dollar threshold may be used to identify compounds which require Notification and must meet the criteria below in order to be covered. Drugs included in the compound must be a covered product.

Claims for patients under the age of 6 will process automatically for First-Lansoprazole, First-Omeprazole, and Omeprazole + Syrspend SF compounding kits. Additional Clinical Rules:

• Supply limits, Step Therapy and/or Prior Authorization may be in place.

3 . References

1. Food and Drug Administration (2014, July 02). Additions and Modifications to the List of Drug Products That Have Been Withdrawn or Removed From the Market for Reasons of Safety and Effectiveness. Retrieved from http://federalregister.gov/a/2014-15371 2. FDA Drug Shortages. Current and Resolved Drug Shortages and Discontinuations Reported to the FDA. Available at: https://www.accessdata.fda.gov/scripts/drugshortages/dsp_SearchResults.cfm 3. ASHP Current Drug Shortages. Available at: https://www.ashp.org/Drug- Shortages/Current-Shortages

4 . Revision History

Page 188 Date Notes

2/26/2021 Added Omeprazole Syrspend + SF compounding kit to criteria. Remov ed note that First Omeprazole and First Lansoprazole are typically excl uded from coverage.

Page 189 Contraceptives

Prior Authorization Guideline

GL-76781 Contraceptives

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 1/1/2021 P&T Approval Date: 1/1/2008 P&T Revision Date: 10/16/2019 ; 10/21/2020

1 . Criteria

Product Name: Contraceptive Medications: Medroxyprogesterone acetate (Depo-Provera), etonogestrel/ethinyl estradiol (NuvaRing), Oral Contraceptives, norelgestromin/ethinyl estradiol (OrthoEvra), Annovera (segesterone/ethinyl estradiol), Twirla Approval Length 12 month(s) Guideline Type Notification

Approval Criteria

1 - Patient is using the medication for non-contraception purposes. Examples include:

• Abnormal or excessive bleeding disorders (e.g., Amenorrhea, oligomenorrhea,

Page 190 menorrhagia, dysfunctional uterine bleeding) • Acne • Decrease in bone mineral density • Dysmenorrhea • Endometriosis • Hirsutism • Irregular Menses/cycles • Ovarian cysts • Perimenopausal symptoms • History of Pelvic Inflammatory Disease (PID) • Polycystic Ovarian Syndrome (PCO or PCOS) • Premenstrual Syndrome (PMS) • Premenstrual Dysphoric Disorder (PMDD) • Prevention of endomentrial and/or ovarian cancer • Prevention of menstrual migraines • Turner's syndrome • Uterine fibroids or adenomyosis

2 . Background

Benefit/Coverage/Program Information

Background:

This program is designed for clients who are grandfathered and/or designated a Religious Exempt organization per the Patient Protection and Affordable Care Act and would like to exclude contraceptive products for contraception purposes.

Additional Clinical Programs:

3 . Revision History

Date Notes

11/10/2020 Annual review. Added Twirla.

Page 191 Corlanor (ivabradine)

Prior Authorization Guideline

GL-78424 Corlanor (ivabradine)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 2/26/2016 P&T Revision Date: 11/15/2019 ; 11/15/2019 ; 11/13/2020

1 . Indications Drug Name: Corlanor (ivabradine) Symptomatic chronic heart failure Indicated to reduce the risk of hospitalization for worsening of heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction less than or equal to 35%, who are in sinus rhythm with resting heart rate greater than or equal to 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.

Dilated cardiomyopathy (DCM) Indicated to treat stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in pediatric patients aged 6 months and older, who are in sinus rhythm with an elevated heart rate.

2 . Criteria

Page 192 Product Name: Corlanor Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - One of the following:

1.1 All of the following:

1.1.1 Worsening heart failure in a diagnosis of stable, symptomatic chronic [e.g. New York Heart Association (NYHA) class II, III or IV] heart failure

AND

1.1.2 Patient has a left ventricular ejection fraction (EF) less than or equal to 35%

AND

1.1.3 The patient is in sinus rhythm

AND

1.1.4 Patient has a resting heart rate greater than or equal to 70 beats per minute

AND

1.1.5 One of the following:

1.1.5.1 Patient is on maximum tolerated doses of beta blockers (e.g., carvedilol, metoprolol succinate, bisoprolol)

1.1.5.2 Patient has a contraindication or intolerance to beta-blocker therapy

Page 193

1.2 All of the following:

1.2.1 Diagnosis of stable symptomatic heart failure due to dilated cardiomyopathy (DCM)

AND

1.2.2 Patient is in sinus rhythm

AND

1.2.3 Patient has an elevated heart rate

Product Name: Corlanor Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Corlanor therapy

3 . Background

Benefit/Coverage/Program Information

Background:

Corlanor (ivabradine) is a hyperpolarization-activated cycle nucleotide-gated channel blocker indicated to reduce the risk of hospitalization for worsening of heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction < 35%, who are in sinus rhythm with resting heart rate > 70 beats per minute and either are on maximally

Page 194 tolerated doses of beta-blockers or have a contraindication to beta-blocker use. It is also indicated to treat stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in pediatric patients aged 6 months and older, who are in sinus rhythm with an elevated heart rate.

Additional Clinical Rules:

Supply Limits may be in place.

4 . References

1. Corlanor [Package Insert] Thousand Oaks, CA: Amgen Inc.; April 2019.

5 . Revision History

Date Notes

12/21/2020 Annual review. Updated references.

Page 195 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (OR, WA, TX)

Prior Authorization Guideline

GL-8033 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (OR, WA, TX)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 10/2/2007

1 . Criteria

Product Name: A drug used for an off-label indication or non-FDA approved indication Guideline Type Administrative

Approval Criteria

1 - Requests will be reviewed on a case-by-case basis by a clinical pharmacist

Page 196

AND

2 - The drug is approved by the FDA

AND

3 - The drug is prescribed by a participating licensed health care professional for the treatment of a life-threatening condition or for a chronic and seriously debilitating condition

AND

4 - The drug is medically necessary to treat the condition

AND

5 - Documented history of failure, intolerance, or contraindication to standard, conventional therapies to treat or manage the disease or condition, where available

AND

6 - The drug has been recognized for treatment of that condition by one of the following:

6.1 Two articles from major peer reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer-reviewed medical journal*

6.2 The American Hospital Formulary Service (AHFS) Drug Information

6.3 The United States Pharmacopoeia Dispensing Information (USPDI)†

Page 197

6.4 The American Medical Association Drug Evaluations† Notes Authorization will be issued for length of therapy or indefinitely as appr opriate. *May not apply to all benefit plans. †The American Medical As sociation Drug Evaluations and USPDI are currently not published.

Page 198 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (UHC of CA)

Prior Authorization Guideline

GL-8031 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (UHC of CA)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 11/18/2008; CPS Revision Date: 12/15/2009

1 . Criteria

Product Name: A drug used for an off-label indication or non-FDA approved indication Guideline Type Administrative

Approval Criteria

1 - Requests will be reviewed on a case-by-case basis by a clinical pharmacist

Page 199

AND

2 - The drug is approved by the FDA

AND

3 - The drug is prescribed by a participating licensed health care professional for the treatment of a life-threatening condition or for a chronic and seriously debilitating condition

AND

4 - The drug is medically necessary to treat the condition

AND

5 - Documented history of failure, intolerance, or contraindication to standard, conventional therapies to treat or manage the disease or condition, where available.

AND

6 - The drug has been recognized for treatment of that condition by one of the following:

6.1 The American Hospital Formulary Service (AHFS) Drug Information

6.2 One of the following compendia as part of an anticancer chemotherapeutic regimen:

• The Elsevier Gold Standard’s Clinical Pharmacology • The National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium • DRUGDEX System by Micromedex

Page 200 OR

6.3 Two articles from major peer reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer-reviewed medical journal. Notes Authorization will be issued for length of therapy or indefinitely as appr opriate

2 . References

1. CA Assembly Bill No. 830. An act to amend Sections 1367.21 and 1370.4 of the Health and Safety Code, to amend Sections 10123.195 and 10145.3 of the Insurance Code, and the amend Sections 14105.43 and 14133.2 of the Welfare and Institutions Code, relating to drugs and devices. Available at: http://info.sen.ca.gov/pub/09- 10/bill/asm/ab_0801-0850/ab_830_bill_20091011_chaptered.pdf Accessed November 11, 2009.

Page 201 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (UHC of OK)

Prior Authorization Guideline

GL-8032 Coverage of Drugs for Off-Label or Non-FDA Approved Indications (UHC of OK)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 10/2/2007; CPS Revision Date: 4/5/2011

1 . Criteria

Product Name: A drug used for an off-label or non-FDA approved non-cancer indication Diagnosis Off-label non-cancer indications Guideline Type Administrative

Approval Criteria

Page 202 1 - Requests will be reviewed on a case-by-case basis by a clinical pharmacist

AND

2 - The drug is approved by the FDA

AND

3 - The drug is prescribed by a participating licensed health care professional for the treatment of a life-threatening condition or for a chronic and seriously debilitating condition

AND

4 - The drug is medically necessary to treat the condition

AND

5 - Documented history of failure, intolerance, or contraindication to standard, conventional therapies to treat or manage the disease or condition, where available

AND

6 - The drug has been recognized for treatment of that condition by one of the following:

6.1 The American Hospital Formulary Service (AHFS) Drug Information under the Therapeutic Uses section

6.2 The United States Pharmacopoeia Dispensing Information (USPDI)†

6.3 The American Medical Association Drug Evaluations†

Page 203

6.4 Two articles from major peer reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer-reviewed medical journal Notes Authorization will be issued for length of therapy or indefinitely as appr opriate. Off-label use may be reviewed for medical necessity and denie d as such if the off-label criteria are not met. Please refer to drug specif ic PA guideline for off-label criteria if available. †The American Medical Association Drug Evaluations and USPDI are currently not published.

Product Name: A drug used for an off-label or non-FDA approved cancer indication Diagnosis Off-label cancer indications Guideline Type Administrative

Approval Criteria

1 - The drug has been recognized for treatment of that condition by one of the following:

1.1 The American Hospital Formulary Service (AHFS) Drug Information under the Therapeutic Uses section

1.2 The Elsevier Gold Standard’s Clinical Pharmacology under the Indications section

1.3 The National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium with a Category of Evidence and Consensus of 1, 2A or 2B (See Table 1 in the Background section)

1.4 DRUGDEX System by Micromedex with a Strength of Recommendation rating of Class I, Class IIa, or Class IIb (See Table 2 in the Background section)

Page 204

1.5 Two articles from major peer-reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there are clear and convincing contradictory evidence presented in a major peer-reviewed journal Notes Authorization will be issued for length of therapy or indefinitely as appr opriate. Off-label use of drugs for the treatment of cancer may be revie wed for medical necessity and denied as such if the off-label criteria ar e not met. Please refer to drug specific PA guideline for off-label criteri a if available.

2 . Background

Clinical Practice Guidelines

NCCN Categories of Evidence and Consensus Table 1: NCCN Categories of Evidence and Consensus

Category Quality of Evidence Level of Consensus 1 High Uniform

2A Lower Uniform 2B Lower Non-uniform 3 Any Major disagreement

Category 1: The recommendation is based on high-level evidence (i.e., high- powered randomized clinical trials or meta-analyses), and the NCCN Guideline Panel has reached uniform consensus that the recommendation is indicated. In this context, uniform means near unanimous positive support with some possible neutral positions.

Category 2A: The recommendation is based on lower level evidence, but despite the absence of higher level studies, there is uniform consensus that the recommendation is appropriate. Lower level evidence is interpreted broadly, and runs the gamut from phase II to large cohort studies to case series to individual practitioner experience. Importantly, in many instances, the retrospective studies are

Page 205 derived from clinical experience of treating large numbers of patients at a member institution, so NCCN Guideline Panel Members have first-hand knowledge of the data. Inevitably, some recommendations must address clinical situations for which limited or no data exist. In these instances the congruence of experience-based judgments provides an informed if not confirmed direction for optimizing patient care. These recommendations carry the implicit recognition that they may be superseded as higher level evidence becomes available or as outcomes-based information becomes more prevalent.

Category 2B: The recommendation is based on lower level evidence, and there is nonuniform consensus that the recommendation should be made. In these instances, because the evidence is not conclusive, institutions take different approaches to the management of a particular clinical scenario. This nonuniform consensus does not represent a major disagreement, rather it recognizes that given imperfect information, institutions may adopt different approaches. A Category 2B designation should signal to the user that more than one approach can be inferred from the existing data.

Category 3: Including the recommendation has engendered a major disagreement among the NCCN Guideline Panel Members. The level of evidence is not pertinent in this category, because experts can disagree about the significance of high level trials. Several circumstances can cause major disagreements. For example, if substantial data exist about two interventions but they have never been directly compared in a randomized trial, adherents to one set of data may not accept the interpretation of the other side's results. Another situation resulting in a Category 3 designation is when experts disagree about how trial data can be generalized. An example of this is the recommendation for internal mammary node radiation in postmastectomy radiation therapy. One side believed that because the randomized studies included this modality, it must be included in the recommendation. The other side believed, based on the documented additional morbidity and the role of internal mammary radiation therapy in other studies, that this was not necessary. A Category 3 designation alerts users to a major interpretation issue in the data and directs them to the manuscript for an explanation of the controversy.

DRUGDEX (Micromedex) Strength of Recommendation Ratings Table 2: Strength of Recommendation

Class Recommendation Description Class I Recommended The given test or treatment has been proven useful, and should be performed or

Page 206 administered. Recommended, In The given test or treatment Most Cases is generally considered to Class IIa be useful, and is indicated in most cases. Class IIb Recommended, in The given test or treatment Some Cases may be useful, and is indicated in some, but not most, cases. Class III Not The given test or treatment Recommended is not useful, and should be avoided Class Evidence Indeterminate Inconclusive

3 . References

1. Oklahoma Statute, Title 63, Article 26, Section 1-2604 - Coverage for Prescription Drugs for Cancer Treatment or Study of Oncology.

Page 207 Daliresp (roflumilast)

Prior Authorization Guideline

GL-76925 Daliresp (roflumilast)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 11/1/2011 P&T Revision Date: 10/16/2019 ; 10/21/2020

1 . Indications Drug Name: Daliresp (roflumilast) Chronic obstructive pulmonary disease (COPD) Indicated for reducing the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

2 . Criteria

Product Name: Daliresp Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Page 208

Approval Criteria

1 - Diagnosis of severe to very severe COPD (i.e., FEV1 less than or equal to 50 percent of predicted)

AND

2 - COPD is associated with chronic bronchitis

AND

3 - History COPD exacerbation(s)

Product Name: Daliresp Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Daliresp therapy

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Programs:

Background:

Page 209 Daliresp (roflumilast) is a phosphodiesterase-4 inhibitor indicated for reducing the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

4 . References

1. Daliresp [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; March 2019. 2. Global strategy for the diagnosis, management and prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2019.

5 . Revision History

Date Notes

11/22/2020 Annual Review. Updated references.

Page 210 DAW Override

Prior Authorization Guideline

GL-87371 DAW Override

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 12/19/2015 P&T Revision Date: 10/16/2019 ; 10/21/2020

Note:

P&T Revision Date: 4/26/2017, 12/19/2018. The intent of this policy is to serve as guidance for clients who would like to implement a dispense as written (DAW) override program. The standard DAW (brand name) override criteria are for clients who opt for such a program to help manage prescription costs. The criteria is applied when a provider/patient requests for coverage of a brand medication when a generic is available.

1 . Criteria

Product Name: Brand drugs with two or more generic equivalents available Approval Length 12 month(s) Guideline Type Administrative

Page 211

Approval Criteria

1 - Patient has tried two generic equivalents of the requested drug from different manufacturers

AND

2 - One of the following:

2.1 Patient has had an allergic reaction or intolerance to an inactive ingredient

2.2 Patient has experienced an inadequate response to the generic equivalent of the requested drug

AND

3 - One of the following:

3.1 Requested drug is FDA-approved for the condition being treated

3.2 If requested for an off-label indication, the off-label guideline approval criteria have been met

Product Name: Brand drugs with only one generic equivalent available Approval Length 12 month(s) Guideline Type Administrative

Approval Criteria

1 - Patient has tried one generic equivalent of the requested drug from a different manufacturer

Page 212 AND

2 - One of the following:

2.1 Patient has had an allergic reaction or intolerance to an inactive ingredient

2.2 Patient has experienced an inadequate response to the generic equivalent of the requested drug

AND

3 - One of the following:

3.1 Requested drug is FDA-approved for the condition being treated

3.2 If requested for an off-label indication, the off-label guideline approval criteria have been met

2 . Endnotes

A. The standard DAW (brand name) override criteria are for clients who opt for such a program to help manage prescription costs. The criteria is applied when a provider/patient requests for coverage of a brand medication when a generic is available. There must be a clinical reason why the patient cannot take the generic version of the medication. Acceptable clinical reasons include having an inadequate response, an allergic reaction, or intolerance to two generic manufacturers of the branded product (or one if only one generic equivalent is available). Intolerance of the generic version may occur due to excipients in the generic version of the product. In order to receive approval for the prescribed drug, the prescriber will document the clinical reason as to why the patient cannot use a generic version of the product.

3 . Revision History

Page 213 Date Notes

5/20/2021 Addition of EHB formulary to guideline, no changes to criteria

Page 214 Devices

Prior Authorization Guideline

GL-90175 Devices

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 4/17/2019 P&T Revision Date: 07/17/2019 ; 04/15/2020 ; 08/14/2020 ; 12/16/2020 ; 02/19/2021 ; 5/21/2021

1 . Criteria

Product Name: Atopaderm*, Eletone*, Entty Spray*, EpiCeram*, Halucort*, HPRPlus*, Hylaguard*, Hylatopic Plus*, KamDoy Rx*, Neocera*, Neosalus*, Nutraseb*, Penlen*, Promiseb*, Synerderm*, and Tetrix* Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type NonFormulary or Prior Authorization

Approval Criteria

Page 215 1 - All of the following:

1.1 Diagnosis of one of the following:

• atopic dermatitis • allergic contact dermatitis • radiation dermatitis

AND

1.2 History of trial and failure or contraindication to two OTC emollients (e.g. Aquaphor, Eucerin, Lubriderm, white petroleum; document name and duration of trial)

AND

1.3 History of trial and failure or contraindication to two topical corticosteroids (document topical corticosteroid name and duration of trial) Notes *Devices are typically excluded from coverage.

Product Name: Aquoral*, Caphosol*, NeutraSal* and SalivaMax* Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type NonFormulary or Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Both of the following:

1.1.1 Diagnosis of xerostomia

AND

1.1.2 History of trial and failure or contraindication to both of the following:

1.1.2.1 Saliva stimulants (e.g. sugar-free hard candies or gum)

Page 216

AND

1.1.2.2 Two OTC saliva substitutes (e.g. Biotene, Mouth Kote, Oasis, SalivaSure, Salivea; document name and duration of trial)

1.2 Both of the following:

1.2.1 Diagnosis of oral mucositis

AND

1.2.2 History of trial and failure or contraindication to both of the following:

• topical lidocaine • salt and sodium bicarbonate rinse

Notes *Devices are typically excluded from coverage.

Product Name: Hyclodex* Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type NonFormulary or Prior Authorization

Approval Criteria

1 - History of trial and failure or contraindication to two OTC antiseptics (e.g. Betadine, Dakin’s Solution, Hibiclens; document name and duration of trial) Notes *Devices are typically excluded from coverage.

Product Name: Aquoral*, Atopaderm*, Caphosol*, Eletone*, Entty Spray*, EpiCeram*, Halucort*, HPRPlus*, Hylaguard*, Hyclodex*, Hylatopic Plus*, KamDoy Rx*, Neocera*, Neosalus*, NeutraSal*, Nutraseb*, Penlen*, Promiseb*, SalivaMax*, Synerderm*, or Tetrix* Approval Length 12 month(s)

Page 217 Therapy Stage Reauthorization Guideline Type NonFormulary or Prior Authorization

Approval Criteria

1 - Documentation of a positive response to therapy. Notes *Devices are typically excluded from coverage.

2 . Background

Benefit/Coverage/Program Information

Background:

The U.S. Food and Drug Administration (FDA) classifies devices as products that are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease that do not achieve their purpose through chemical action and are not dependent on metabolism to achieve their purpose. Devices are typically benefit exclusions. This program only applies when devices are covered by the plan.

Additional Clinical Rules:

3 . References

1. U.S. Food and Drug Administration. Classify Your Medical Device. Last updated 3/22/2018. Retrieved from https://www.fda.gov/medical-devices/overview-device- regulation/classify-your-medical-device. Accessed February 2020. 2. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014 Jul;71(1):116-32. 3. Schneider L, Tilles S, Lio P, et al. Atopic dermatitis: A practice parameter update 2012. J Allergy Clin Immunol 2013;131:295-9. 4. McGuire D, Fulton J, Park J, et al. Systematic review of basic oral care for the management of oral mucositis in cancer patients. Support Care Cancer 2013 (31); 3165- 3177.

Page 218

4 . Revision History

Date Notes

7/21/2021 5/2021 P&T - Updated program name to include prior authorization.

Page 219 Diabetes Medications - SGLT2 Inhibitors - Step Therapy

Prior Authorization Guideline

GL-71234 Diabetes Medications - SGLT2 Inhibitors - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 10/26/2016 P&T Revision Date: 02/14/2020 ; 05/15/2020 ; 07/15/2020 ; 7/15/2020

1 . Indications Drug Name: Farxiga, Invokana, Jardiance, and Steglatro Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Drug Name: Invokana Type 2 diabetes mellitus Indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD), and to reduce the risk of end- stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria > 300 mg/day.

Drug Name: Jardiance Type 2 diabetes mellitus Indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Page 220 Drug Name: Invokamet, Invokamet XR, Synjardy, Synjardy XR, Segluromet and Xigduo XR Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing metformin or a SGLT2 inhibitor or in patients already being treated with both a SGLT2 inhibitor and metformin.

Drug Name: Glyxambi, Qtern, and Steglujan Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both a SGLT2 and a DPP4 inhibitor is appropriate.

Drug Name: Farxiga Heart Failure Indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction.

2 . Criteria

Product Name: Farxiga* [a] Diagnosis Heart failure with a reduced ejection fraction Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a trial resulting in therapeutic failure, contraindication or intolerance to three of the following:

• Angiotensin converting enzyme (ACE) inhibitor (e.g., lisinopril) • Angiotensin receptor blocker (e.g., losartan) • Angiotensin receptor blocker/neprilysin inhibitor (i.e., Entresto) • Beta-blocker (e.g., metoprolol) • Diuretic (e.g., furosemide) • Spironolactone

AND

Page 221 2 - History of a trial resulting in therapeutic failure, contraindication or intolerance to Jardiance Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Farxiga, Invokana, Invokamet, Invokamet XR, Qtern, Segluromet, Steglatro, Steglujan and Xigduo XR are typically excluded from covera ge. Tried/failed criteria may be in place. Please refer to plan specifics t o determine coverage status.

Product Name: Jardiance [a] Diagnosis Heart failure with a reduced ejection fraction Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a trial resulting in therapeutic failure, contraindication or intolerance to three of the following:

Product Name: Glyxambi [a] or Jardiance [a] Diagnosis All other indications Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - One of the following:

Page 222

1.1 History of failure, contraindication or intolerance to metformin (generic Glucophage, Glucophage XR)

1.2 Currently on therapy with Glyxambi or Jardiance and is requesting continuation of the same therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Farxiga* [a], Invokana* [a], or Steglatro* [a] Diagnosis All other indications Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a three month trial resulting in therapeutic failure, contraindication or intolerance to both of the following:

1.1 Metformin (generic Glucophage, Glucophage XR)

AND

1.2 Jardiance Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. *Farxiga, Invokana, Invokamet, Invokamet XR, Qtern, Segluromet, S teglatro, Steglujan and Xigduo XR are typically excluded from coverag e. Tried/failed criteria may be in place. Please refer to plan specifics to determine coverage status.

Product Name: Invokamet* [a], Invokamet XR* [a], Xigduo XR* [a], or Segluromet* [a] Diagnosis All other indications

Page 223 Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a three month trial resulting in therapeutic failure, contraindication or intolerance to Synjardy/Synjardy XR Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Farxiga, Invokana, Invokamet, Invokamet XR, Qtern, Segluromet, Steglatro, Steglujan and Xigduo XR are typically excluded from covera ge. Tried/failed criteria may be in place. Please refer to plan specifics t o determine coverage status.

Product Name: Qtern* [a], or Steglujan* [a] Diagnosis All other indications Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a three month trial resulting in therapeutic failure, contraindication or intolerance to both of the following:

1.1 Metformin (generic Glucophage, Glucophage XR)

AND

1.2 Glyxambi Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Farxiga, Invokana, Invokamet, Invokamet XR, Qtern, Segluromet, Steglatro, Steglujan and Xigduo XR are typically excluded from covera ge. Tried/failed criteria may be in place. Please refer to plan specifics t o determine coverage status.

Page 224 3 . Background

Benefit/Coverage/Program Information

Background:

Farxiga (dapagliflozin)*, Invokana (canagliflozin)*, Jardiance (empagliflozin) and Steglatro (ertugliflozin)* are sodium-glucose co-transporter 2 (SGLT2) inhibitors indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Farxiga*, Invokana* and Jardiance have additional indications. Farxiga* is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction. Invokana* is indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD), and to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria > 300 mg/day. Jardiance is indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Invokamet (canagliflozin/metformin)*, Invokamet XR (canagliflozin/metformin extended- release)*, Synjardy (empagliflozin/metformin), Synjardy XR (empagliflozin/metformin extended- release), Segluromet (ertugliflozin/metformin)* and Xigduo XR (dapagliflozin/metformin extended-release)* are SGLT2 inhibitors and biguanide combination medications indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing metformin or a SGLT2 inhibitor or in patients already being treated with both a SGLT2 inhibitor and metformin.

Glyxambi (empagliflozin/linagliptan), Qtern (dapagliflozin/saxagliptin)* and Steglujan (ertugliflozin/sitagliptin) are combination SGLT2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both a SGLT2 and a DPP4 inhibitor is appropriate.

If a member has a prescription for metformin, Glyxambi or Jardiance in the claims history within the previous 12 months, the claim for Glyxambi or Jardiance will automatically process. Members currently on Glyxambi or Jardiance as documented in claims history will be allowed to continue on their current therapy. Members new to therapy will be required to meet the coverage criteria below.

Additional Clinical Rules:

Page 225 • Supply limits may be in place.

* Farxiga, Invokana, Invokamet, Invokamet XR, Qtern, Segluromet, Steglatro, Steglujan and Xigduo XR are typically excluded from coverage. Tried/failed criteria may be in place. Please refer to plan specifics to determine coverage status.

4 . References

1. Jardiance prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. January 2020. 2. Invokana Prescribing Information. Janssen Pharmaceuticals, Inc. Titusville, NJ. January 2020. 3. Farxiga Prescribing Information. AstraZeneca Pharmaceuticals LP. Wilmington, DE. May 2020. 4. Steglatro prescribing information. Merck & Co., Inc. Whitehouse Station, NJ. January 2020. 5. Invokamet/Invokamet XR prescribing information. Janssen Pharmaceuticals, Inc. Titusville, NJ. January 2020. 6. Synjardy/Synjardy XR prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. January 2020. 7. Segluromet prescribing information. Merck & Co., Inc. Whitehouse Station, NJ. January 2020. 8. Xigduo XR prescribing information. AstraZeneca Pharmaceuticals LP. Wilmington, DE. February 2020. 9. Glyxambi prescribing information. Boehringer Ingelheim Pharmaceutials, Inc. Ridgefield, CT. March 2020. 10. Qtern prescribing information. AstraZeneca Pharmaceuticals LP. Wilmington, DE. January 2020. 11. Steglujan prescribing information. Merck & Co., Inc. Whitehouse Station, NJ. January 2020. 12. American Diabetes Association. Standard of Medical Care in Diabetes- 2019. Diabetes Care 2020;43 (Supplement 1) 13. Yancy, CW, Jessup, M, Bozkurt, B, et.al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017; 136(6): e137-61.

5 . Revision History

Date Notes

8/7/2020 Added step requirements for heart failure indication.

Page 226 Diabetic Agents

Prior Authorization Guideline

GL-90560 Diabetic Agents

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 1/13/2003 P&T Revision Date: 03/18/2020 ; 05/14/2020 ; 06/16/2021

1 . Indications Drug Name: Actoplus Met XR (pioglitazone/metformin extended-release) Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate. Limitations of Use: 1) pioglitazone exerts its antihyperglycemic effect only in the presence of endogenous insulin. Actoplus Met XR should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings; 2) use caution in patients with liver disease

Drug Name: Riomet (metformin), Riomet ER (metformin extended release) Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.

Drug Name: Avandia (rosiglitazone) Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of use: 1) Avandia should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; 2)

Page 227 Coadministration of Avandia and insulin is not recommended.

Drug Name: Cycloset (bromocriptine) Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of use: 1) Cycloset should not be used to treat type 1 diabetes or diabetic ketoacidosis; 2) Limited efficacy data in combination with thiazolidinediones; 3) Efficacy has not been confirmed in combination with insulin.

2 . Criteria

Product Name: Actoplus Met XR, Avandia, Cycloset, Riomet, Riomet ER Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - Trial and failure, intolerance or contraindication to one of the following generics:

• metformin • metformin ER • glipizide-metformin • glyburide-metformin • pioglitazone-metformin

3 . References

1. Actoplus Met XR Prescribing Information. Takeda Pharmaceuticals America Inc., December 2017. 2. Avandia Prescribing Information. GlaxoSmithKline. Research Triangle Park, NC. November 2020. 3. Cycloset Prescribing Information. VeroScience, LLC. Tiverton, RI. August 2020. 4. Riomet Prescribing Information. Mikart, Inc. Atlanta, GA. December 2018. 5. Riomet ER Prescribing Information. Sun Pharmaceutical Industries, Inc. Cranbury, NJ. August 2019.

4 . Revision History

Page 228

Date Notes

8/2/2021 Annual review: background updates, no changes to clinical criteria

Page 229 Dihydroergotamine nasal spray (Migranal), Ergomar (ergotamine)

Prior Authorization Guideline

GL-42455 Dihydroergotamine nasal spray (Migranal), Ergomar (ergotamine)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 3/21/2018; P&T Revision Date: 3/21/2018; **Guideline Effective Date: 6/1/2018**

1 . Indications Drug Name: Migranal (dihydroergotamine) nasal spray Migraine headaches Indicated for the acute treatment of migraine headaches with or without aura. Migranal nasal spray is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.

Drug Name: Ergomar (ergotamine) Vascular headache Indicated to abort or prevent vascular headache, e.g., migraine, migraine variants or a so-called "histaminic cephalalgia". Ergomar should not be used for chronic daily administration.

Page 230

2 . Criteria

Product Name: [Dihydroergotamine Nasal Spray (Migranal*)] [a] Approval Length 12 Month Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe migraine headaches with or without aura.

AND

2 - History of failure, contraindication, or intolerance to one oral triptan (e.g., almotriptan [Axert], naratriptan [Amerge], sumatriptan [Imitrex]). Document medication(s) and date(s) of trial.

AND

3 - History of failure, contraindication, or intolerance to one nasal triptan (e.g., sumatriptan nasal spray [generic Imitrex]). Document medication(s) and date(s) of trial. Notes *Brand Migranal is typically excluded from coverage. [a] State mandate s may apply. Any federal regulatory requirements and the member spe cific benefit plan coverage may also impact coverage criteria. Other pol icies and utilization management programs may apply.

Product Name: Ergomar (ergotamine) [a] Approval Length 12 Month Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe migraine headaches with or without aura.

Page 231 AND

2 - History of failure, contraindication, or intolerance to two oral triptans (e.g., almotriptan [Axert], naratriptan [Amerge], sumatriptan [Imitrex]). Document medication(s) and date(s) of trial. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

The U.S. Headache Consortium guidelines offer a general strategy based on expert consensus. Nonsteroidal anti-inflammatory drugs (NSAIDs) or caffeine-containing combination analgesics may be first-line treatment for mild to moderate migraine, or severe migraine that has previously responded to these agents. Triptans are considered first-line abortive treatment of moderate to severe migraine, or mild attacks that have not responded to nonprescription medicines. Ergotamine-containing compounds may also be reasonable in this situation.

This program requires a member to try one oral triptan and one nasal triptan prior to receiving coverage for brand or generic Migranal or two oral triptans prior to receiving coverage of Ergomar.

Additional Clinical Programs:

*Brand Migranal is typically excluded from coverage.

Supply limits may apply.

4 . References

1. Migranal prescribing information. Valeant Pharmaceuticals North America LLC. Bridgewater, NJ. August 2017.

Page 232 2. Ergomar prescribing information. TerSera Therapeutics. Cedar Rapids IA. November 2016. 3. Acute treatment of migraine in adults. Up-to-date. 2017. 4. Gilmore B., Michael M. Treatment of acute migraine headache. Am Fam Physician. 2011 Feb 1;83(3):271-80.

Page 233 Dihydroergotamine nasal spray (Migranal), Ergomar (ergotamine) - PA/Med Nec

Prior Authorization Guideline

GL-81159 Dihydroergotamine nasal spray (Migranal), Ergomar (ergotamine) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 4/26/2017 P&T Revision Date: 01/15/2020 ; 1/20/2021

2 . Criteria

Page 234 Product Name: [Dihydroergotamine Nasal Spray (Migranal*)] [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe migraine headaches with or without aura.

AND

2 - History of failure, contraindication, or intolerance to one of the following oral triptans (Document duration of trial):

• almotriptan (Axert) • eletriptan (Relpax) • frovatriptan (Frova) • naratriptan (Amerge) • rizatriptan (Maxalt/Maxalt MLT) • sumatriptan (Imitrex) • zolmitriptan (Zomig)

AND

3 - History of failure, contraindication, or intolerance to sumatriptan nasal spray (generic Imitrex nasal spray) Notes *Brand Migranal is typically excluded from coverage. [a] State mandate s may apply. Any federal regulatory requirements and the member spe cific benefit plan coverage may also impact coverage criteria. Other pol icies and utilization management programs may apply.

Product Name: Ergomar (ergotamine) [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe migraine headaches with or without aura.

Page 235

AND

2 - History of failure, contraindication, or intolerance to two of the following oral triptans (Document duration of trial):

• almotriptan (Axert) • eletriptan (Relpax) • frovatriptan (Frova) • naratriptan (Amerge) • rizatriptan (Maxalt/Maxalt MLT) • sumatriptan (Imitrex) • zolmitriptan (Zomig)

3 . Background

Benefit/Coverage/Program Information

Background:

Migranal (dihydroergotamine) nasal spray is indicated for the acute treatment of migraine headaches with or without aura. Migranal nasal spray is not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine. Ergomar is indicated to abort or prevent vascular headache, for example, migraine, migraine variants or a so-called "histaminic cephalalgia”. Ergomar should not be used for chronic daily administration.

This program requires a member to try one oral triptan and one nasal triptan prior to receiving coverage for brand or generic Migranal or two oral triptans prior to receiving coverage of

Page 236 Ergomar.

Additional Clinical Programs:

*Brand Migranal is typically excluded from coverage.

4 . References

1. Migranal [package insert]. Bridgewater, NJ: Bausch Health US, LLC.; July 2019. 2. Ergomar [package insert]. Deerfield, IL; TerSera Therapeutics; February 2020. 3. Gilmore B., Michael M. Treatment of acute migraine headache. Am Fam Physician. 2011 Feb 1;83(3):271-80.

5 . Revision History

Date Notes

2/19/2021 Annual review, updated references.

Page 237 Dojolvi (triheptanoin) - PA/Med Nec

Prior Authorization Guideline

GL-79258 Dojolvi (triheptanoin) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 10/21/2020 P&T Revision Date: 12/16/2020

1 . Indications Drug Name: Dojolvi Long-Chain Fatty Acid Oxidation Disorders Indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).

2 . Criteria

Product Name: Dojolvi [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 238

Approval Criteria

1 - Submission of medical records confirming the diagnosis of long-chain fatty acid oxidation disorders (LC-FAOD) with at least two of the following diagnostic criteria:

• Disease specific elevation of acylcarnitines on a newborn blood spot or in plasma • Low enzyme activity in cultured fibroblasts • One or more known pathogenic mutations in CPT2, ACADVL, HADHA, or HADHB

AND

2 - Patient is not receiving Dojolvi in combination with any other medium-chain triglyceride (MCT) products

AND

3 - Prescribed by a board certified medical geneticist experienced in the treatment of long-chain fatty acid oxidation disorders (LC-FAOD)

AND

4 - Target recommended daily dosage does not exceed 35% of the patient’s total prescribed daily caloric intake (DCI)

AND

5 - Patient is receiving disease related dietary management

AND

6 - If not diagnosed by newborn screening, patient has a history of clinical manifestations of long-chain fatty acid oxidation disorders LC-FAOD (e.g., rhabdomyolysis) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 239

Product Name: Dojolvi [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Dojolvi therapy (e.g., increased cardiac efficiency, decreased left ventricular wall mass, decreased incidence of rhabdomyolysis, etc.)

AND

2 - Patient is not receiving Dojolvi in combination with any other medium-chain triglyceride (MCT) product

AND

3 - Prescribed by a board certified medical geneticist experienced in the treatment of long-chain fatty acid oxidation disorders (LC-FAOD)

AND

4 - Target recommended daily dosage does not exceed 35% of the patient’s total prescribed daily caloric intake (DCI)

AND

5 - Patient is receiving disease related dietary management Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 240 3 . Background

Benefit/Coverage/Program Information

Background: Dojolvi (triheptanoin) is a medium-chain triglyceride indicated as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). Additional Clinical Rules:

4 . References

1. Dojolvi [package insert]. Novato, CA: Ultragenyx Pharmaceutical, Inc.; June 2020.

5 . Revision History

Date Notes

1/6/2021 Change to prescriber requirement criteria.

Page 241 Doxepin Cream - PA/Med Nec

Prior Authorization Guideline

GL-87044 Doxepin Cream - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 4/21/2021

P&T Revision Date:

1 . Indications Drug Name: Prudoxin (doxepin), Zonalon (doxepin) Atopic dermatitis, Lichen simplex chronicus. Indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus.

2 . Criteria

Product Name: Prudoxin (doxepin), Zonalon (doxepin) [a] Diagnosis Atopic dermatitis, Lichen simplex chronicus Approval Length 1 month(s) Guideline Type Prior Authorization

Page 242

Approval Criteria

1 - Prudoxin* or Zonalon* will be approved based on one of the following criteria:

1.1 Both of the following:

1.1.1 Diagnosis of moderate pruritus due to atopic dermatitis

AND

1.1.2 History of failure, contraindication, or intolerance to one of the following topical therapies:

• One topical corticosteroid [e.g., mometasone furoate, fluocinolone acetonide (generic Synalar), fluocinonide] • One topical calcineurin inhibitor [e.g., pimecrolimus (generic Elidel), tacrolimus (generic Protopic)]

1.2 Both of the following:

1.2.1 Diagnosis of moderate pruritus due to lichen simplex chronicus

AND

1.2.2 History of failure, contraindication, or intolerance to a topical corticosteroid [e.g., mometasone furoate, fluocinolone acetonide (generic Synalar), fluocinonide] Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Page 243 Background: Prudoxin and Zonalon cream are indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus.

The American Academy of Dermatology guidelines for the care and management of atopic dermatitis recommend topical corticosteroids for patients with atopic dermatitis who have failed to respond to standard nonpharmacologic therapy. The use of topical calcineurin inhibitors (tacrolimus, pimecrolimus) is also recommended in patients who have failed to respond to, or who are not candidates for topical corticosteroid treatment. Doxepin may provide a short-term decrease in pruritus, however has no significant reduction in disease severity or control. Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place, • *Brand Prudoxin and Zonalon are typically excluded from coverage.

4 . References

1. Prudoxin [package insert]. San Antonio, TX: DPT Laboratories, Ltd; June 2017. 2. Zonalon [package insert]. San Antonio, TX: DPT Laboratories, Ltd; June 2017. 3. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014; 71(1):116-32.

5 . Revision History

Date Notes

5/19/2021 New program.

Page 244 DPP4 Inhibitors - Step Therapy - All ASO, Non-NY Fully Insured, Non-NJ Fully Insured, and Non-CT Fully Insured

Prior Authorization Guideline

GL-88420 DPP4 Inhibitors - Step Therapy - All ASO, Non-NY Fully Insured, Non-NJ Fully Insured, and Non-CT Fully Insured

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 10/26/2016 P&T Revision Date: 10/16/2019 ; 04/15/2020 ; 05/15/2020 ; 5/21/2021

1 . Indications Drug Name: Janumet (sitagliptin/metformin), Janumet XR (sitagliptin/metformin extended-release) Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin/metformin extended-release is appropriate.

Drug Name: Januvia (sitagliptin) Type 2 diabetes mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

2 . Criteria

Page 245

Product Name: Januvia* [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a three month trial resulting in a therapeutic failure, contraindication (e.g. risk factors for heart failure), or intolerance to both of the following (list reason for therapeutic failure, contraindication, or intolerance) [b]:

1.1 Tradjenta (linagliptin)

AND

1.2 One of the following:

• Nesina (alogliptin) • Onglyza (saxagliptin)

Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required. *Typically excluded from coverage

Product Name: Janumet* [a], Janumet XR* [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of a three month trial resulting in a therapeutic failure, contraindication (e.g. risk factors for heart failure), or intolerance to all of the following (list reason for therapeutic failure, contraindication, or intolerance) [b]:

1.1 Jentadueto (linagliptin/metformin immediate-release)/Jentadueto XR (linagliptin/metformin extended-release)

Page 246

AND

1.2 One of the following:

• Kazano (alogliptin/metformin immediate-release) • Kombiglyze XR (saxagliptin/metformin extended-release)

Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required. *Typically excluded from coverage

3 . Background

Benefit/Coverage/Program Information

Background:

Januvia (sitagliptin)* is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Janumet (sitagliptin/metformin) and Janumet XR (sitagliptin/metformin extended-release)* are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin/metformin extended-release is appropriate.

*Typically excluded from coverage

Additional Clinical Rules:

4 . References

1. Januvia [package insert]. Whitehouse Station, NJ: Merck & CO. Inc.; December 2020. 2. Janumet [package insert]. Whitehouse Station, NJ: Merck & CO. Inc.; December 2020.

Page 247 3. Janumet XR [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; December 2020. 4. American Diabetes Association. Standard of Medical Care in Diabetes - 2021. Diabetes Care 2021;44 (Supplement 1)

5 . Revision History

Date Notes

6/15/2021 Annual review. Updated references.

Page 248 Dry Eye Disease – PA/Med Nec

Prior Authorization Guideline

GL-87097 Dry Eye Disease – PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 3/1/2006 P&T Revision Date: 04/15/2020 ; 4/21/2021

1 . Indications Drug Name: Cequa (cyclosporine 0.09% ophthalmic solution) Keratoconjunctivitis sicca Indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.

Drug Name: Restasis and Restasis Multidose (cyclosporine 0.05% ophthalmic emulsion) Keratoconjunctivitis sicca Indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.

Drug Name: Xiidra (lifitegrast 5% ophthalmic solution) Dry eye disease (DED) Indicated for the treatment of the signs and symptoms of dry eye disease (DED).

Page 249 2 . Criteria

Product Name: Restasis [a] or Xiidra [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Tear deficiency associated with ocular inflammation due to one of the following:

• Moderate to severe keratoconjuctivitis sicca • Moderate to severe dry eye disease

AND

2 - Not prescribed to manage dry eyes peri-operative elective eye surgery (e.g., LASIK)

AND

3 - History of failure to at least one OTC artificial tear product (e.g., Systane Ultra, Akwa Tears, Refresh Optive, Soothe XP)

AND

4 - Prescribed by or in consultation with one of the following:

• Ophthalmologist • Optometrist • Rheumatologist

Product Name: Restasis [a] or Xiidra [a]

Page 250 Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient has demonstrated clinically significant improvement with therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Cequa* [a] or Restasis MultiDose* [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Tear deficiency associated with ocular inflammation due to one of the following:

• Moderate to severe keratoconjuctivitis sicca • Moderate to severe dry eye disease

AND

2 - Not prescribed to manage dry eyes peri-operative elective eye surgery (e.g., LASIK)

AND

3 - History of failure to at least one OTC artificial tear product (e.g., Systane Ultra, Akwa Tears, Refresh Optive, Soothe XP)

AND

Page 251 4 - History of failure, contraindication or intolerance to Restasis single dose vials

AND

5 - Prescribed by or in consultation with one of the following:

• Ophthalmologist • Optometrist • Rheumatologist

Product Name: Cequa* [a] or Restasis MultiDose* [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Benefit/Coverage/Program Information

Background: Cequa™ (cyclosporine 0.09% ophthalmic solution)*, Restasis® (cyclosporine 0.05% ophthalmic emulsion) and Restasis MultiDose (cyclosporine 0.05% ophthalmic

Page 252 emulsion)* are indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.

Xiidra™ (lifitegrast 5% ophthalmic solution) is indicated for the treatment of the signs and symptoms of dry eye disease. Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place • Prior Authorization – Notification may be in place • Compound and Bulk powder notification may be in place

4 . References

1. Cequa [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; January 2021. 2. Restasis [package insert]. Irvine, CA: Allergan, Inc.; July 2017. 3. Restasis MultiDose [package insert]. Irvine, CA: Allergan, Inc.; October 2016. 4. Xiidra [package insert]. Hanover, NJ: Novartis Pharmaceuticals Corporation: June 2020. 5. American Academy of Ophthalmology. Dry Eye Syndrome Preferred Practice Pattern 2018. Accessed March 1, 2021.

5 . Revision History

Date Notes

5/18/2021 Annual review. Updated references

Page 253 Dulera (mometasone furoate/formoterol fumarate) - Step Therapy

Prior Authorization Guideline

GL-76596 Dulera (mometasone furoate/formoterol fumarate) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 2/16/2016 P&T Revision Date: 10/21/2020

1 . Indications Drug Name: Dulera (mometasone furoate/formoterol fumarate) Asthma Indicated for the treatment of asthma in patients aged 5 and older.

2 . Criteria

Product Name: Dulera [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

Page 254

1 - History of failure, contraindication, or intolerance to both of the following:

1.1 Symbicort

AND

1.2 One of the following:

1.2.1 fluticasone/salmeterol [fluticasone/salmeterol (AirDuo RespiClick*), Advair (HFA or Diskus)*]

1.2.2 Breo Ellipta Notes * Brand AirDuo RespiClick, Dulera, and fluticasone/salmeterol Diskus ( generic Advair Diskus) are typically excluded from coverage. [a] State mandates may apply. Any federal regulatory requirements and the me mber specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background:

Dulera* (mometasone furoate/formoterol fumarate) is indicated for the treatment of asthma in patients aged 5 and older. Dulera should be used in patients not adequately controlled on a long-term asthma-control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta2-adrenergic agonist.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try Symbicort and either fluticasone/salmeterol [fluticasone/salmeterol (AirDuo RespiClick*) or Advair (HFA or Diskus)] or Breo Ellipta before providing coverage for Dulera for the treatment of asthma.

Additional Clinical Programs

Page 255 • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

• Supply limits may also be in place.

4 . References

1. Advair Diskus [package insert]. Research Triangle Park, NC: GlaxoSmithKline; January 2019. 2. Advair HFA[package insert]. Research Triangle Park, NC: GlaxoSmithKline; February 2019. 3. AirDuo RespiClick [package insert]. Parsippany, NJ: Teva Respiratory LLC.; February 2020. 4. Breo Ellipta [package insert]. Research Angle Park, NC: GlaxoSmithKline; January 2019. 5. Dulera [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; August 2020. 6. Symbicort [package insert]. Wilmington, DE: AstraZeneca; July 2019

5 . Revision History

Date Notes

11/23/2020 Annual Review. Updated references.

Page 256 Duopa (carbidopa/levodopa) - PA/Med Nec

Prior Authorization Guideline

GL-75373 Duopa (carbidopa/levodopa) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 7/14/2015 P&T Revision Date: 09/18/2019 ; 9/16/2020

1 . Indications Drug Name: Duopa (carbidopa/levodopa) Advanced Parkinson's disease Indicated for the treatment of motor fluctuations in patients with advanced Parkinson's disease.

2 . Criteria

Product Name: Duopa [a] Approval Length 12 Months Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 257

Approval Criteria

1 - Diagnosis of advanced Parkinson's Disease

AND

2 - Patient experiences a wearing "off" phenomenon that cannot be managed by increasing the dose of oral levodopa

AND

3 - Has undergone or has planned placement of a procedurally-placed tube Notes [a]State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply .

Product Name: Duopa [a] Approval Length 12 Months Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Duopa therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Page 258 Background:

Duopa (carbidopa/levodopa) enteral suspension is indicated for the treatment of motor fluctuations in patients with advanced Parkinson’s disease.

Duopa should be administered continuously via an infusion pump over 16 hours through a procedurally-placed tube. Duopa may be administered through a naso-jejunal (NJ) tube for a short period of time until a gastrostomy tube can be placed.

Additional Clinical Rules:

4 . References

1. Duopa [package insert]. North Chicago, IL: AbbVie, Inc.; May 2020. 2. Sara Varanese, Zoe Birnbaum, Roger Rossi, and Alessandro Di Rocco, “Treatment of Advanced Parkinson's Disease,” Parkinson’s Disease, vol. 2010, Article ID 480260, 9 pages, 2010. doi:10.4061/2010/480260. 3. International Parkinson and Movement Disorder Society Evidence-Based Medicine Review: Update on Treatments for the Motor Symptoms of Parkinson’s Disease. Movement Disorders. 2018.

5 . Revision History

Date Notes

10/29/2020 Annual review. Updated references.

Page 259 Elidel (pimecrolimus), Protopic (tacrolimus) - Step Therapy

Prior Authorization Guideline

GL-77666 Elidel (pimecrolimus), Protopic (tacrolimus) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 9/27/2017 P&T Revision Date: 08/16/2019 ; 09/16/2020 ; 12/16/2020

1 . Indications Drug Name: Elidel (pimecrolimus) Mild to moderate atopic dermatitis Indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non- immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable.

Drug Name: Protopic (tacrolimus) Moderate to severe atopic dermatitis Indicated as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non- immunocompromised adults and children, who have failed to respond adequately to other topical prescription treatments for atopic dermatitis or when those treatments are not advisable.

2 . Criteria

Page 260

Product Name: [Elidel, Protopic] [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - One of the following:

1.1 History of failure, contraindication, or intolerance to one topical corticosteroid^

1.2 Drug is being prescribed for the facial or groin area Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. ^Tried/failed alternative(s) are supported by FDA labeling

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Programs:

Background:

Elidel (pimecrolimus) is indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. Protopic (tacrolimus) is indicated as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non-immunocompromised adults and children, who

Page 261 have failed to respond adequately to other topical prescription treatments for atopic dermatitis or when those treatments are not advisable.

Both Elidel and Protopic have demonstrated efficacy in the treatment of plaque psoriasis, and the American Academy of Dermatology recommend Elidel and Protopic for specific cases of facial and intertriginous psoriasis or situations where a topical corticosteroid may be associated with skin atrophy3.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. If a member has a prescription for a topical corticosteroid in claim’s history in the previous 365 days, the prescription for Elidel or Protopic will process automatically. Elidel or Protopic as documented in claims history will be allowed continued coverage of their current therapy. Members new to therapy will be required to meet the below criteria.

4 . References

1. Elidel [Package Insert]. Bridgewater, NJ: Valeant Pharmaceuticals Inc; December 2017. 2. Protopic [Package Insert]. Northbrook, IL: Astellas Pharma US, Inc; February 2019. 3. Menter A, Korman NJ, et al. “Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies.” J Am Acad Dermatol 2009;60:643-59.

5 . Revision History

Date Notes

11/30/2020 Annual Review. Updated references.

Page 262 Elmiron (pentosan polysulfate sodium) - Step Therapy

Prior Authorization Guideline

GL-79328 Elmiron (pentosan polysulfate sodium) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 12/16/2020

P&T Revision Date:

1 . Indications Drug Name: Elmiron Relief of bladder pain or discomfort associated with interstitial cystitis. Indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.

2 . Criteria

Product Name: Elmiron [a] Approval Length 12 month(s) Guideline Type Step Therapy

Page 263 Approval Criteria

1 - History of failure, contraindication, or intolerance to amitriptyline. Notes a State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact coverage c riteria. Other policies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background: Elmiron is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.

Step therapy programs are utilized to encourage use of lower cost alternatives for certain therapeutic classes. This program requires a trial of amitriptyline before providing coverage for Elmiron. Additional Clinical Rules:

4 . References

1. Elmiron [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; June 2020. 2. Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome: American Urological Associations (AUA) Guideline. 2014. 3. Management of interstitial cystitis/bladder pain syndrome. UpToDate, July 2020. Accessed November 2020.

5 . Revision History

Date Notes

Page 264 1/6/2021 New program

Page 265 Endari (L-glutamine Powder for Solution) - PA/Med Nec

Prior Authorization Guideline

GL-81810 Endari (L-glutamine Powder for Solution) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 11/17/2017 P&T Revision Date: 02/14/2020 ; 2/19/2021

1 . Indications Drug Name: Endari (L-glutamine Powder for Solution) Acute complications of sickle cell disease Indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.

2 . Criteria

Product Name: Endari Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 266

Approval Criteria

1 - Both of the following:

• Diagnosis of sickle cell disease • Used to reduce acute complications of sickle cell disease

AND

2 - One of the following:

• Patient is using Endari with concurrent hydroxyurea therapy • Patient is unable to take hydroxyurea due to a contraindication or intolerance

AND

3 - Patient has had 2 or more painful sickle cell crises within the past 12 months

AND

4 - History of failure to non-prescription L-glutamine supplementation

Product Name: Endari Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Endari therapy

3 . Background

Page 267 Benefit/Coverage/Program Information

Background:

Endari (L-glutamine powder for solution) is indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. The recommended dose is 5 to 15 grams orally twice daily based on body weight.

Additional Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply Limits may be in place

4 . References

1. Endari [package insert]. Emmaus Medical, Inc. Torrance, CA. October 2020.

5 . Revision History

Date Notes

3/19/2021 Annual review. Updated references.

Page 268 Enspryng (satralizumab-mwge) - PA/Med Nec

Prior Authorization Guideline

GL-76784 Enspryng (satralizumab-mwge) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 1/1/2021 P&T Approval Date: 10/21/2020

P&T Revision Date:

1 . Indications Drug Name: Enspryng Neuromyelitis Optica Specturm Disorder (NMOSD) Indicated in adult patients who are anti- aquaporin-4 (AQP4) antibody positive.

2 . Criteria

Product Name: Enspryng [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 269

Approval Criteria

1 - Diagnosis of neuromyelitis optica spectrum disorder (NMOSD)

AND

2 - Patient has a positive serologic test for anti-aquaporin-4 (AQP4) antibodies

AND

3 - History of failure, contraindication, or intolerance to rituximab therapy

AND

4 - One of the following:

4.1 History of one or more relapses that required rescue therapy during the previous 12 months

4.2 History of two or more relapses that required rescue therapy during the previous 24 months

AND

5 - Prescribed by, or in consultation with, a neurologist

AND

6 - Patient is not receiving Enspryng in combination with any of the following:

Page 270 • Anti-IL6 therapy [e.g., Actemra (tocilizumab)] • B-cell depletion therapy [e.g. rituximab, Uplizna (inebilizumb-cdon)]

Product Name: Enspryng [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Enspryng therapy

AND

2 - Prescribed by, or in consultation with, a neurologist

AND

3 - Patient is not receiving Enspryng in combination with any of the following:

• Disease modifying therapies for the treatment of multiple sclerosis [e.g., Gilenya (fingolimod), Tecfidera (dimethyl fumarate), Ocrevus (ocrelizumab), etc.] • Complement inhibitors [e.g., Soliris (eculizumab)] • Anti-IL6 therapy [e.g., Actemra (tocilizumab)] • B-cell depletion therapy [e.g. rituximab, Uplizna (inebilizumb-cdon)]

3 . Background

Page 271

Benefit/Coverage/Program Information

Background

Enspryng (satralizumab-mwge) is an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti- aquaporin-4 (AQP4) antibody positive.

Additional Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place.

4 . References

1. Enspryng [package insert]. South San Francisco, CA: Genentech, Inc.; August 2020. 2. Sellner J1, Boggild M, Clanet M, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Aug;17(8):1019-32. 3. Sato D, Callegaro D, Lana-Peixoto MA, Fujihara K. Treatment of neuromyelitis optica: an evidence based review. Arq Neuropsiquiatr 2012;70(1);59-66. 4. Ciron J, Audoin B, Bourre B, et al. Recommendations for the use of rituximab in neuromyelitis optica spectrum disorders. Rev Neurol (Paris). 2018 Apr;174(4):255-264. 5. Nikoo Z, Badihian S, Shaygannejad V, et al. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial. J Neurol. 2017 Sep;264(9):2003-2009. 6. Gao F, Chai B, Gu C, et al. Effectiveness of rituximab in neuromyelitis optica: a meta- analysis. BMC Neurol. 2019 Mar 6;19(1):36. 7. Kim SH, Huh SY, Lee SJ, et al. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. 8. Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114-2124. 9. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412.

5 . Revision History

Date Notes

11/10/2020 New program.

Page 272

Page 273 Entresto (valsartan-sacubitril) - PA/Med Nec

Prior Authorization Guideline

GL-86696 Entresto (valsartan-sacubitril) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 8/19/2015 P&T Revision Date: 11/15/2019 ; 11/13/2020 ; 4/21/2021

1 . Indications Drug Name: Entresto (valsartan-sacubitril) Chronic Heart Failure Indicated to reduce the risk of cardiovascular death and hospitalization for heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. It is also indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

2 . Criteria

Product Name: Entresto [a] Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 274 Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 As continuation of therapy initiated during an inpatient stay

1.2 Both of the following:

1.2.1 Diagnosis of pediatric heart failure with systemic left ventricular systolic dysfunction which is symptomatic

AND

1.2.2 Prescribed by or in consultation with a cardiologist

1.3 All of the following:

1.3.1 Diagnosis of heart failure (with or without hypertension)

AND

1.3.2 One of the following:

1.3.2.1 Both of the following:

1.3.2.1.1 Ejection fraction is less than or equal to 40 percent

AND

1.3.2.1.2 One of the following:

Page 275 • Patient is on a stabilized dose and receiving concomitant therapy with bisoprolol, carvedilol, or metoprolol • Patient has an intolerance or contraindication to beta-blockers

1.3.2.2 Both of the following:

• Ejection fraction greater than 40 percent • Patient has structural heart disease (i.e. left atrial enlargement (LAE) or left ventricular hypertrophy (LVH)

AND

1.3.3 Heart failure is classified as one of the following:

• New York Heart Association Class II • New York Heart Association Class III • New York Heart Association Class IV

AND

1.3.4 Patient does not have a history of angioedema

AND

1.3.5 Patient will discontinue any use of concomitant ACE Inhibitor or ARB before initiating treatment with Entresto. ACE inhibitors must be discontinued at least 36 hours prior to initiation of Entresto

AND

1.3.6 Patient is not concomitantly on aliskiren therapy

AND

Page 276

1.3.7 Entresto is prescribed by, or in consultation with, a cardiologist Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Entresto [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - The Entresto dose has been titrated to a dose of 97 mg/103 mg twice daily, or to a maximum dose as tolerated by the patient

AND

2 - Documentation of positive clinical response to therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Background:

Page 277 Entresto (valsartan-sacubitril) is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. It is also indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

4 . References

1. Entresto [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2021. 2. McMurray JJ, Desai AS, Gong J. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). European Journal of Heart Failure 2013; 15: 1062-1073. 3. McMurray JJ, Packer M, Desai AS, et al. Angio-tensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004. 4. Yancy CW, Jessup M, Bozkurt B, , et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation 2013; 128:e240-e327. 5. 5. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137- e161.

5 . Revision History

Date Notes

5/11/2021 Updated criteria to allow coverage with ejection fraction greater than 4 0% with structural heart disease based on updated labeling.

Page 278 Erectile Dysfunction Agents

Prior Authorization Guideline

GL-32699 Erectile Dysfunction Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 5/18/2012; P&T Revision Date: 12/21/2016 **Effective: 12/6/2016**

1 . Indications Drug Name: Levitra (vardenafil), Muse (alprostadil), Staxyn (vardenafil), Stendra (avanafil), and Viagra (sildenafil) Erectile dysfunction Indicated for the treatment of erectile dysfunction (ED).

Drug Name: Cialis (tadalafil) Erectile Dysfunction Indicated for the treatment of erectile dysfunction (ED)

Benign Prostatic Hyperplasia Indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Limitation of use: If Cialis is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks because the incremental benefit of Cialis decreases from 4 weeks until 26 weeks, and the incremental benefit of Cialis beyond

Page 279 26 weeks is unknown.

Erectile Dysfunction and Benign Prostatic Hyperplasia Indicated for the treatment of ED and the signs and symptoms of BPH (ED/BPH). Limitation of use: If Cialis is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks because the incremental benefit of Cialis decreases from 4 weeks until 26 weeks, and the incremental benefit of Cialis beyond 26 weeks is unknown.

2 . Criteria

Product Name: Cialis (2.5 mg, 5 mg, 10 mg, 20 mg), Levitra, Muse, Staxyn, Stendra, or Viagra Diagnosis Erectile Dysfunction Guideline Type Prior Authorization or Non-Formulary

Approval Criteria

1 - Provided it is not a benefit exclusion

AND

2 - Diagnosis of organic erectile dysfunction as defined by one of the following:

2.1 Both of the following:

2.1.1 The patient has an underlying condition [e.g., atherosclerosis, cardiac disease (e.g., hypertension, peripheral arterial disease), diabetes, central nervous system disease, multiple sclerosis, renal disease, hypogonadism, history of cystectomy, prostate cancer, spinal injuries] [6-7]

AND

2.1.2 Physician confirmation that the underlying condition is causing the patient's ED [6,7]

2.2 All of the following:

Page 280

2.2.1 The patient's ED is caused by one of the following drugs:

• Cardiovascular drugs [eg, thiazide diuretics, Aldactone (spironolactone), Aldomet (methyldopa), Catapres (clonidine), Wytensin (guanabenz), Tenex (guanfacine), Tenormin (atenolol), Lopressor/Toprol XL (metoprolol), Visken (pindolol), Inderal (propranolol), Cardura (doxazosin), Minipress (prazosin), Hytrin (terazosin), Dibenzyline (phenoxybenzamine), Apresoline (hydralazine), Adalat/Procardia (nifedipine), Cardizem/Tiazac (diltiazem), Calan/Verelan (verapamil), Norpace (disopyramide)] [8] • Anticonvulsants [eg, Tegretol (carbamazepine), Dilantin (phenytoin)] [8] • Antidepressants [eg, TCAs, SSRIs, Desyrel (trazodone), MAO inhibitors] [7] • Antipsychotics [eg, phenothiazines] [7] • Anxiolytics [eg, short-acting barbiturates, benzodiazepines] [7] • Gastrointestinal drugs [eg, Tagamet (cimetidine), Zantac (ranitidine), Reglan (metoclopramide)] [7]

AND

2.2.2 Physician confirmation that the drug is causing the patient's ED [6,7]

AND

2.2.3 ED-causing drug cannot be discontinued or switched [6,7] Notes Cialis, Levitra, Staxyn, Stendra, and Viagra are NOT indicated for the tr eatment of pulmonary arterial hypertension (PAH). Adcirca and Revatio are the only PDE-5 inhibitors currently FDA-approved for the treatment of PAH. Adcirca and Revatio may require prior authorization.

Product Name: Cialis 2.5 mg or Cialis 5 mg Diagnosis Benign Prostatic Hyperplasia (BPH) Guideline Type Prior Authorization or Non-Formulary

Approval Criteria

1 - Diagnosis of benign prostatic hyperplasia (BPH)

AND

2 - History of failure, contraindication or intolerance to two alpha blockers [e.g., Flomax

Page 281 (tamsulosin), Rapaflo (silodosin), Uroxatral (alfuzosin)] Notes Cialis is NOT indicated for the treatment of pulmonary arterial hyperten sion (PAH). Adcirca and Revatio are the only PDE-5 inhibitors currently FDA-approved for the treatment of PAH. Adcirca and Revatio may req uire prior authorization.

3 . Definitions

Definition Description

Organic erectile A consequence of chronic medical conditions that results in impaired dysfunction arterial blood flow or nerve damage, mixed organic/psychogenic causes, or necessary use of medications that cannot be reduced or discontinued. [6-7]

4 . References

1. Cialis Prescribing Information. Eli Lilly and Company, April 2014. 2. Levitra Prescribing Information. Bayer HealthCare Pharmaceuticals Inc., April 2014. 3. Viagra Prescribing Information. Pfizer Inc., March 2015. 4. Muse Prescribing Information. Meda Pharmaceuticals Inc., August 2012. 5. Drug Facts and Comparisons. Available at: http://www.efactsonline.com. Accessed July 10, 2008 6. Merck Manuals Online Medical Library. The Merck Manual for Healthcare Professionals. Available at http://www.merckmanuals.com/professional/genitourinary_disorders/male_sexual_dysfu nction/erectile_dysfunction.html. Accessed September 25, 2013. 7. Thompson JF. Geriatric Urologic disorder. Applied Therapeutics. 8th Edition 2005; 101:5-101:6. 8. Current Medical Diagnosis & Treatment - 44th Ed. (2005) 23. Urology. Marshall L. Stoller, & Peter R. Carroll, MD. Urologic evaluation, male erectile dysfunction. 9. Eardley I, Gentile V, Austoni E, et al. Efficacy and safety of tadalafil in a western European population of men with erectile dysfunction. BJU International 2004;94:871- 877. 10. Porst H, Nathan HD, Guillano F, et al. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Adult Urology 2003;62(1):121-125. 11. Steif C, Porst H, Saenz de Tejada I, et al. Sustained efficacy and tolerability with vardenafil over 2 years of treatment in men with erectile dysfunction. Int J Clin Pract 2004;58(3):230-239. 12. Hellstrom WJG, Gittelman, M, Karlin G, et al. Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology 2003:61(Suppl4A0:8-14.

Page 282 13. Montorsi F, Nathan HP, McCullough A, et al. Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. J Urol 2004;172:1036-1041. 14. Goldstein I, Lue TF, Padma-Nathan, H, et al. Oral sildenafil in the treatment of erectile dysfunction. NEJM 1998;338(20):1397-1404. 15. Nathan HP, Hellstrom WJG, Kaiser FE, et al. Treatment of Men with Erectile Dysfunction with Transurethral Alprostadil. NEJM 1997;336(1):1-7. 16. Saenz de Tejada I, Knight JR, Anglin G, et al. Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care 2002;25(12):2159-2164. 17. Goldstein I, Young JM, Fischer J, et al. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes. Diabetes Care 2003; 26(3):777-783. 18. Rendell MS, Rajfer J, Wicker PA, et al. Sildenafil for treatment of erectile dysfunction in men with diabetes. JAMA 1999;281(5):421-426. 19. Montorsi F, McDermott TED, Morgan R, et al. Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies. Adult Urology 1999;53(5):1011-1018. 20. Brock G, Nehra A, Lipschultz, LI, et al. Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy. Journal of Urology 2003;170:1278-1283. 21. Raina R, Lakin MM, Agarwal A, et al. Efficacy and factors associated with successful outcome of sildenafil citrate use for erectile dysfunction after radical prostatectomy. Adult Urology 2004;63(5):960-966. 22. Giuliano F, Hutling C, Masry WE, et al. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. American Neuro Assoc 1999;46(1):15-21. 23. Carson C, Hatzichristou DG, Carrier S, et al. Erectile response with vardenafil in sildenafil nonresponders: a multicentre, double-blind, 12-week, flexible dose, placebo- controlled erectile dysfunction clinical trial. BJU International 2004; 94:1301-1309. 24. American Urological Association (AUA). The management of erectile dysfunction clinical guideline: an update. Available at: http://www.auanet.org/content/guidelines-and-quality- care/clinical- guidelines.cfm?sub=ed&CFID=1476624&CFTOKEN=33685075&jsessionid=843061e21 52ab9f3e9ac623e262f62962407. Accessed April 13, 2010. 25. AACE Male Sexual Dysfunction Task force. American Association of clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Male Sexual Dysfunction: A Couple’s Problem-2003 Update. Endocrine Practice. Vol 9 No. 1 January/February 2003 Available at: http://www.aace.com/pub/pdf/guidelines/sexdysguid.pdf. Accessed April 13, 2010. 26. Rajfer J, Aliotta PJ, Steidle CP et al. Tadalafil dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US. Int J Impot Res. 2007;19(1):95-103. 27. American College of Physicians (ACP). Hormonal testing and pharmacological treatment of erectile dysfunction: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2009;151(9):1-12. 28. Staxyn Prescribing Information. Bayer HealthCare Pharmaceuticals Inc., April 2014. 29. Stendra Prescribing Information. VIVUS, Inc. January 2015. 30. American Heart Association (AHA). Sexual activity and cardiovascular disease. http://circ.ahajournals.org/content/early/2012/01/19/CIR.0b013e3182447787.full.pdf. Accessed July 18, 2012. 31. American Urological Association. Guideline on the management of benign prostatic hyperplasia (revised 2010). Available at http://www.auanet.org/content/clinical-practice-

Page 283 guidelines/clinical-guidelines/main-reports/bph- management/chap_1_GuidelineManagementof(BPH).pdf. Accessed September 18, 2012. 32. Per clinical consult, March 16, 2012.

Page 284 Eucrisa (crisaborole) - Step Therapy

Prior Authorization Guideline

GL-72494 Eucrisa (crisaborole) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/26/2017 P&T Revision Date: 07/15/2020 ; 7/15/2020

1 . Indications Drug Name: Eucrisa (crisaborole) Mild to moderate atopic dermatitis Indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 3 months of age and older.

2 . Criteria

Product Name: Eucrisa* [a] Diagnosis All Diagnoses Approval Length 12 month(s) Guideline Type Step Therapy

Page 285

Approval Criteria

1 - One of the following:

1.1 History of failure, contraindication, or intolerance to ONE of the following topical therapies:

1.2 Both of the following:

1.2.1 Patient is currently on Eucrisa therapy

AND

1.2.2 Patient has not received a manufacturer supplied sample at no cost in the prescriber's office, or any form of assistance from the Pfizer sponsored Eucrisa 4 you program (e.g., sample card which can be redeemed at a pharmacy for a free supply of medication) as a means to establish as a current user of Eucrisa* Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. *Patients requesting initial authorization who were established on the rapy via the receipt of a manufacturer supplied sample at no cost in the prescriber's office or any form of assistance from the Pfizer sponsored Eucrisa 4 you program shall be required to meet initial authorization crit eria as if patient were new to therapy.

3 . Background

Benefit/Coverage/Program Information

Background: Step therapy programs are utilized to encourage use of lower cost alternatives for

Page 286 certain therapeutic classes. This program requires a member to try one or more preferred topical products before providing coverage for Eucrisa (crisaborole).

Eucrisa (crisaborole) is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 3 months of age and older.

The American Academy of Dermatology guidelines for the care and management of atopic dermatitis recommend topical corticosteroids for patients with atopic dermatitis who have failed to respond to standard nonpharmacologic therapy. They also recommend the use of topical calcineurin inhibitors (tacrolimus, pimecrolimus) in patients who have failed to respond to, or who are not candidates for topical corticosteroid treatment. Eucrisa is not included in the guidelines.

Pimecrolimus (generic Elidel®) is indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non- immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable.

Tacrolimus (generic Protopic®) is indicated as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non- immunocompromised adults and children, who have failed to respond adequately to other topical prescription treatments for atopic dermatitis or when those treatments are not advisable.

Patients currently on Eucrisa therapy as documented in claims history will be allowed to continue on their current therapy. For patients with claims history documenting prior use of either topical corticosteroids or topical calcineurin inhibitors, a prescription for Eucrisa will automatically process. Additional Clinical Rules:

4 . References

1. Eucrisa [package insert]. Anacor Pharmaceuticals. Palo Alto, CA. March 2020.

Page 287 2. Elidel [package insert]. Valeant Pharmaceuticals. Bridgewater, NJ. August 2014. 3. Protopic [package insert]. Astellas Pharma US, Inc. Northbrook, IL May 2012. 4. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014; 71(1):116-32.

5 . Revision History

Date Notes

8/27/2020 Changed step from trial of two to trial of one. Updated reference.

Page 288 Exforge (amlodipine/valsartan), Exforge HCT (amlodipine/valsartan/HCTZ)

Prior Authorization Guideline

GL-13119 Exforge (amlodipine/valsartan), Exforge HCT (amlodipine/valsartan/HCTZ)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 10/2/2007; CPS Revision Date: 7/14/2015

1 . Indications Drug Name: Exforge (amlodipine and valsartan) Hypertension Indicated for the treatment of hypertension, to lower blood pressure: (1) In patients not adequately controlled on monotherapy; (2) As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

Drug Name: Exforge HCT (amlodipine, valsartan, hydrochlorothiazide) Hypertension Indicated for the treatment of hypertension to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes, and myocardial infarctions. Not indicated for initial therapy.

Page 289

2 . Criteria

Product Name: Brand Exforge, Generic amlodipine/valsartan, or Brand Exforge HCT Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following:

• ACE Inhibitor • ACE Inhibitor / HCTZ Combination • ACE Inhibitor / Calcium Channel Blocker (CCB) Combination • Candesartan • Irbesartan or Irbesartan / HCTZ • Losartan or Losartan / HCTZ • Telmisartan

Notes Exforge or Exforge HCT may be approved for patients who have tried a n ARB or ARB combination.

3 . References

1. Exforge Prescribing Information. Novartis Pharmaceuticals Corp., September 2014. 2. Exforge HCT Prescribing Information. Novartis Pharmaceuticals Corp., September 2014.

Page 290 Extina (ketoconazole) – Step Therapy

Prior Authorization Guideline

GL-73122 Extina (ketoconazole) – Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 8/14/2020

P&T Revision Date:

1 . Indications Drug Name: Extina (ketoconazole) foam Seborrheic Dermatitis Indicated for the treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older.

2 . Criteria

Product Name: Extina[a] Diagnosis Seborrheic Dermatitis Approval Length 1 month(s) Guideline Type Step Therapy

Page 291

Approval Criteria

1 - Patient has a history of failure, contraindication, or intolerance to one of the following:

• ciclopirox (generic ciclopirox gel, generic Loprox) • ketoconazole shampoo (generic Nizoral)

3 . Background

Benefit/Coverage/Program Information

Background:

Extina (ketoconazole) foam is indicated for the treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older. The safety and efficacy of Extina for treatment of fungal infections has not been established.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try ciclopirox or ketoconazole shampoo prior to receiving coverage for Extina.

4 . References

1. Extina [package insert]. San Antonio, TX: DPT Laboratories, Ltd; August 2018. 2. Del Rosso, James Q. Adult Seborrheic Dermatitis: A Status Report on Practical Topical Management. J Clin Aesthet Dermatol. 2011;4(5):32–38.

Page 292

5 . Revision History

Date Notes

9/10/2020 New program.

Page 293 Fanapt (iloperidone), Fanapt Pack (iloperidone), Vraylar (cariprazine) - Step Therapy

Prior Authorization Guideline

GL-68187 Fanapt (iloperidone), Fanapt Pack (iloperidone), Vraylar (cariprazine) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2020 P&T Approval Date: 3/20/2019 P&T Revision Date: 5/15/2020

1 . Indications Drug Name: Fanapt (iloperidone) Schizophrenia Indicated for the treatment of schizophrenia.

Drug Name: Vraylar (cariprazine) Schizophrenia Indicated for the treatment of schizophrenia.

Bipolar I Disorder Indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder.

Bipolar Depression Indicated for the treatment of depressive episodes associated with bipolar I disorder.

Page 294 2 . Criteria

Product Name: [Fanapt, Fanapt Pack, or Vraylar] [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Step Therapy

Approval Criteria

1 - One of the following:

1.1 History of failure, contraindication, or intolerance to at least two of the following (please document drug, date and duration of trial):

• aripiprazole • olanzapine • quetiapine immediate-release or extended-release • risperidone • Saphris • ziprasidone

1.2 Treatment with Fanapt, Fanapt Pack, or Vraylar was initiated at a recent behavioral inpatient admission (discharge within the past 3 months) and the member is currently stable on therapy. (Please document date of discharge from inpatient admission). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: [Fanapt, Fanapt Pack, or Vraylar] [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Step Therapy

Approval Criteria

Page 295 1 - Documentation of positive clinical response to therapy. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. Fanapt (iloperidone) is FDA approved for the treatment of schizophrenia. Vraylar (cariprazine) is FDA approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder, for the treatment of depressive episodes associated with bipolar I disorder, and for the treatment of schizophrenia.

For the treatment of schizophrenia, treatment guidelines recommend the use of any atypical antipsychotic (with the exception of clozapine) as first-line. For the acute treatment of bipolar I disorder (mania or mixed episodes), the American Psychiatric Association (APA) recommends treatment with lithium plus an antipsychotic or valproate plus an antipsychotic. For less ill patients, monotherapy with lithium, valproate, or an antipsychotic may be sufficient. Atypical antipsychotics are generally preferred over traditional antipsychotics.

This program requires a member to try two atypical antipsychotics (choices include aripiprazole, risperidone, olanzapine, ziprasidone, Saphris, quetiapine IR or quetiapine ER) before providing coverage for Fanapt or Fanapt Pack for schizophrenia or for Vraylar for schizophrenia or bipolar I disorder.

Additional Clinical Rules:

Page 296 • Supply limits may also be in place.

4 . References

1. Fanapt [Prescribing Information]. Washington, D.C., Vanda Pharmaceuticals Inc. February 2017. 2. Vraylar [Prescribing Information]. Madison, NJ:Allergan USA, Inc. May 2019. 3. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia Second Edition. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizop hrenia.pdf 4. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder. Second Edition. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar. pdf

5 . Revision History

Date Notes

6/26/2020 5/2020 P&T - Annual review. Combined quetiapine IR and ER into one Step One option. Added reauthorization criteria. Updated references.

Page 297 Fentanyl Transmucosal

Prior Authorization Guideline

GL-76613 Fentanyl Transmucosal

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 4/17/2019 P&T Revision Date: 10/16/2019 ; 10/21/2020

1 . Indications Drug Name: Abstral, Actiq, Fentora, Lazanda, Subsys, and fentanyl citrate lozenges (generic Actiq) Breakthrough cancer pain Indicated for the management of breakthrough cancer pain in patients who are already receiving and have developed tolerance to around-the-clock opioid therapy for their underlying persistent cancer pain.

2 . Criteria

Product Name: Fentanyl citrate lozenges (generic Actiq) [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Page 298

Approval Criteria

1 - One of the following:

1.1 Submission of medical records demonstrating all of the following:

1.1.1 Use is for the management of breakthrough pain associated with a cancer diagnosis (cancer diagnosis must be documented in the medical records).

AND

1.1.2 Patient must have at least a one week history of one of the following medications to demonstrate tolerance to opioids:

• Morphine sulfate at a dose of greater than or equal to 60 mg/day • Fentanyl transdermal patch at a dose of greater than or equal to 25 mcg/hr • Oxycodone at a dose of greater than or equal to 30 mg/day • Oral hydromorphone at a dose of greater than or equal to 8 mg/day • Oral oxymorphone at a dose of greater than or equal to 25 mg/day • An alternative opioid at an equianalgesic dose (e.g., oral methadone greater than or equal to 20 mg/day)

AND

1.1.3 The patient is currently taking a long-acting opioid around the clock for cancer pain.

AND

1.1.4 One of the following:

1.1.4.1 The patient is not concurrently receiving an alternative transmucosal fentanyl product.

1.1.4.2 The patient is currently receiving an alternative transmucosal fentanyl product AND the prescriber is requesting the termination of all current authorizations for alternative transmucosal fentanyl products in order to begin treatment with the requested medication. Only one transmucosal fentanyl product will be approved at a time. If previous authorizations cannot

Page 299 be terminated, the PA request will be denied.

1.2 The patient is currently taking fentanyl citrate lozenges (generic Actiq) and does not meet the notification criteria requirements based on the FDA-approved indication for breakthrough cancer pain (a one-time fill may be approved for transition to an alternative treatment). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Lazanda [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Submission of medical records demonstrating all of the following:

1.1.1 Use is for the management of breakthrough pain associated with a cancer diagnosis (cancer diagnosis must be documented in the medical records)

AND

1.1.2 Patient must have at least a one week history of one of the following medications to demonstrate tolerance to opioids:

AND

Page 300

1.1.3 The patient is currently taking a long-acting opioid around the clock for cancer pain

AND

1.1.4 One of the following:

1.1.4.1 The patient has a history of failure, contraindication, or intolerance to fentanyl citrate lozenges (generic Actiq)

1.1.4.2 Documentation that the patient is unable to swallow, has dysphagia, esophagitis, mucositis, or uncontrollable nausea/vomiting

AND

1.1.5 One of the following:

1.1.5.1 The patient is not concurrently receiving an alternative transmucosal fentanyl product

1.1.5.2 The patient is currently receiving an alternative transmucosal fentanyl product AND the prescriber is requesting the termination of all current authorizations for alternative transmucosal fentanyl products in order to begin treatment with the requested medication. Only one transmucosal fentanyl product will be approved at a time. If previous authorizations cannot be terminated, the PA request will be denied.

1.2 The patient is currently taking Lazanda and does not meet the notification criteria requirements based on the FDA-approved indication for breakthrough cancer pain (a one-time fill may be approved for transition to an alternative treatment). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 301

Product Name: [Abstral*, Actiq* (brand only), Fentora*, Subsys*] [a] Approval Length 12 month(s) Guideline Type Non Formulary or Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Submission of medical records demonstrating all of the following:

1.1.1 Use is for the management of breakthrough pain associated with a cancer diagnosis (cancer diagnosis must be documented in the medical records)

AND

1.1.2 Patient must have at least a one week history of one of the following medications to demonstrate tolerance to opioids:

AND

1.1.3 The patient is currently taking a long-acting opioid around the clock for cancer pain

AND

1.1.4 The patient has a history of failure, contraindication, or intolerance to fentanyl citrate lozenges (generic Actiq)

AND

Page 302 1.1.5 The patient has a history of failure, contraindication, or intolerance to Lazanda

AND

1.1.6 One of the following:

1.1.6.1 The patient is not concurrently receiving an alternative transmucosal fentanyl product

1.1.6.2 The patient is currently receiving an alternative transmucosal fentanyl product AND the prescriber is requesting the termination of all current authorizations for alternative transmucosal fentanyl products in order to begin treatment with the requested medication. Only one transmucosal fentanyl product will be approved at a time. If previous authorizations cannot be terminated, the PA request will be denied.

1.2 The patient is currently taking Abstral*, Actiq*, Fentora*, or Subsys* and does not meet the notification criteria requirements based on the FDA-approved indication for breakthrough cancer pain (a one-time fill may be approved for transition to an alternative treatment). Notes *Abstral, Actiq (Brand ONLY), fentanyl bulk powder, Subsys and Fento ra are typically excluded from coverage. Please refer to plan specifics t o determine coverage status. [a] State mandates may apply. Any feder al regulatory requirements and the member specific benefit plan covera ge may also impact coverage criteria. Other policies and utilization ma nagement programs may apply.

Product Name: [Fentanyl citrate bulk powder* or compounded fentanyl] [a] Approval Length 12 month(s) Guideline Type Non Formulary or Prior Authorization

Approval Criteria

1 - One of the following criteria:

1.1 Submission of medical records demonstrating all of the following:

1.1.1 Use is for the management of breakthrough pain associated with a cancer diagnosis

Page 303 (cancer diagnosis must be documented in the medical records)

AND

1.1.2 Patient must have at least a one week history of one of the following medications to demonstrate tolerance to opioids:

AND

1.1.3 The patient is currently taking a long-acting opioid around the clock for cancer pain

AND

1.1.4 A unique dosage form is required for a product that is not commercially available due to patient’s age or weight

AND

1.1.5 One of the following:

1.1.5.1 The patient is not concurrently receiving an alternative transmucosal fentanyl product

Page 304 OR

1.2 The patient is currently taking a compounded fentanyl citrate product and does not meet the notification criteria requirements based on the FDA-approved indication for breakthrough cancer pain (a one-time fill may be approved for transition to an alternative treatment). Notes *Abstral, Actiq (Brand ONLY), fentanyl bulk powder, Subsys and Fento ra are typically excluded from coverage. Please refer to plan specifics t o determine coverage status. [a] State mandates may apply. Any feder al regulatory requirements and the member specific benefit plan covera ge may also impact coverage criteria. Other policies and utilization ma nagement programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background:

Abstral, Actiq, Fentora, Lazanda, Subsys, and fentanyl citrate lozenges (generic Actiq) are rapid-acting opioid analgesics indicated for the management of breakthrough cancer pain in patients who are already receiving and have developed tolerance to around-the-clock opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine daily, at least 25 mcg/hour of transdermal fentanyl, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily, at least 25 mg of oral oxymorphone daily or an equianalgesic dose of another opioid for a week or longer. Patients must remain on around-the-clock opioids while taking a rapid-acting fentanyl product. Abstral, Actiq, Fentora, Lazanda, Subsys and fentanyl citrate lozenges (generic Actiq) must not be used in opioid non-tolerant patients because life-threatening hypoventilation could occur at any dose in patients not on a chronic regimen of opiates.

Compounded fentanyl preparations may provide a unique delivery for certain patient-specific conditions and administration requirements. Compounded fentanyl preparations should be made for a single individual and not produced on a large scale. Compounded fentanyl preparations should not be covered if it is being prescribed as an alternative for a commercially available fentanyl product. Therefore, additional criteria will be provided for fentanyl citrate compounds.

Additional Clinical Programs:

• Supply limits may be in place. • Compound and Bulk powder notification may be in place

Page 305 • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Abstral [package insert]. Lake Oswego, OR: Galena Biopharma. November 2014. 2. Actiq [package insert]. North Wales, PA: Cephalon; October 2019. 3. Fentora [package insert]. North Wales, PA: Cephalon; October 2019. 4. Lazanda [package insert]. Newark, CA: Depomed, Inc.; December 2017. 5. Subsys [package insert]. Chandler, AZ: Insys Therapeutics; February 2020. 6. Swarm R, Paice JA, Anghelescu DL, et al. NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain. Version 3.2019. . Accessed September 5, 2019.

5 . Revision History

Date Notes

11/4/2020 Annual review. Clarified submission of cancer diagnosis. Updated refer ences.

Page 306 Fiasp (insulin aspart) - Nonformulary

Prior Authorization Guideline

GL-81163 Fiasp (insulin aspart) - Nonformulary

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 1/20/2021

P&T Revision Date:

1 . Indications Drug Name: Fiasp Type II Diabetes Indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

2 . Criteria

Product Name: Fiasp* [a] Approval Length 12 month(s) Guideline Type Non Formulary

Page 307 Approval Criteria

1 - Patient is less than 18 years of age

AND

2 - History of failure after at least a three month trial [b], contraindication, or intolerance (list reason for therapeutic failure, contraindication, or intolerance) to Humalog Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required. * Fiasp is typically excluded from coverage.

3 . Background

Benefit/Coverage/Program Information

Background:

The American Diabetes Association recommends insulin therapy for Type II diabetes when the appropriate step wise non-insulin approach has failed to lower HbA1c. In Type I diabetes insulin monotherapy is the appropriate treatment. The ADA does not differentiate between brands of insulin but does make recommendations for the initiation of basal insulins or intermediate to short acting insulins.

Additional Clinical Rules:

4 . References

1. American Diabetes Association: Standards of Medical Care in Diabetes. Clinical Diabetes. 2020 Jan 38(1): 10-38. 2. Fiasp [package insert]. Plainsboro, NJ: Novo Nordisk Inc. December 2019.

Page 308

5 . Revision History

Date Notes

2/25/2021 New program.

Page 309 Fibric Acid Derivatives

Prior Authorization Guideline

GL-30093 Fibric Acid Derivatives

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 11/20/1998; P&T Revision Date: 11/18/2015 **Effective 7/1/2016**

1 . Indications Drug Name: Fenofibrates (Fenoglide and Triglide) Primary Hypercholesterolemia and Mixed Dyslipidemia Indicated as adjunctive therapy to diet to reduce elevated LDL-C, Total-C, triglycerides and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia.

Severe Hypertriglyceridemia Indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually reduce fasting triglycerides and eliminate chylomicronemia thereby obviating the need forpharmacologic intervention. Markedly elevated levels of serum triglycerides (eg, > 2000 mg/dL) may increase the risk of developing pancreatitis. The effect of fenofibrate therapy on reducing this risk has not been adequately studied.

Page 310

2 . Criteria

Product Name: Fenoglide, Brand Fenofibrate tablets (40 mg, 120 mg), or Brand Triglide Guideline Type Step Therapy

Approval Criteria

1 - History of both of the following:

1.1 One of the following generics:

• fenofibrate micronized capsule • fenofibrate tablet (except 40 and 120 mg) • fenofibric capsule • fenofibric acid tablet

AND

1.2 Lipofen

3 . References

1. Fenoglide Prescribing Information. Shore Therapeutics. October 2012. 2. Triglide Prescribing Information. Shionogi Pharma, April 2015.

Page 311 Flurazepam

Prior Authorization Guideline

GL-6004 Flurazepam

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 7/10/2012

1 . Indications Drug Name: Flurazepam [1] Insomnia Is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakening. Flurazepam can be used effectively in patients with recurring insomnia or poor sleeping habits, and in acute or chronic medical situations requiring restful sleep. Sleep laboratory studies have objectively determined that flurazepam is effective for at least 28 consecutive nights of drug administration. Since insomnia is often transient and intermittent short-term use is usually sufficient. Prolonged use of hypnotics is usually not indicated and should only be undertaken concomitantly with appropriate evaluation of the patient.

Page 312 2 . Criteria

Product Name: Flurazepam* Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of insomnia Notes * Flurazepam is only recommended for patients < 65 years old. [3-4, A]

3 . Background

Clinical Practice Guidelines

American Academy of Sleep Medicine – Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults (2008) [2] Pharmacological Treatment

According to the American Academy of Sleep Medicine guideline for the management of chronic insomnia (2008), the choice of pharmacologic agent should be based on the following factors: symptom pattern, treatment goals, past treatment, patient preference, cost, availability of other treatments, comorbid conditions, contraindications, concurrent medication interactions, and AEs. The short/intermediate-acting benzodiazepine receptor agonists (BzRAs) (eg, zolpidem, eszopiclone, zaleplon, temazepam) or ramelteon are recommended as initial therapy. No specific agent within this group is considered preferable to the others, as each has been shown to have positive effects on sleep latency, total sleep time, and/or wake time after sleep onset (WASO) in placebo-controlled trials. However, individual patients may respond differently to these medications. For example, zaleplon and ramelteon have very short half-lives and consequently are likely to reduce sleep latency but have little effect on WASO; they are also unlikely to result in residual sedation. Eszopiclone and temazepam have relatively longer half-lives, are more likely to improve sleep maintenance, and are more likely to produce residual sedation. Triazolam has been associated with rebound anxiety and thus is not considered a first-line hypnotic. For patients who prefer not to use a DEA- scheduled drug and for patients with a history of substance use disorders, ramelteon may be an appropriate option. In the event that a patient does not respond well to the initial agent, a different agent within the same class is

Page 313 appropriate.

Selection of the alternative drug should be based on the patient’s response to the first. For instance, a patient who continues to complain of WASO might be prescribed a drug with a longer half-life or a patient who complains of residual sedation might be prescribed a shorter-acting drug. The choice of a specific BzRA may include longer-acting hypnotics, such as estazolam. Flurazepam is rarely prescribed because of its extended half-life. Benzodiazepines not specifically approved for insomnia (eg, lorazepam, clonazepam) might also be considered if the duration of action is appropriate for the patient’s presentation or if the patient has a comorbid condition that might benefit from these drugs. When accompanied with comorbid depression or in the case of other treatment failures, sedating low-dose antidepressants may next be considered. Examples of these drugs include trazodone, mirtazapine, doxepin, amitriptyline, and trimipramine. Although the guideline states that evidence for their efficacy when used alone is relatively weak and that no specific agent within this group is recommended as preferable to the others in this group, it should be noted that low-dose doxepin was not yet FDA- approved at the time these recommendations were published. Chloral hydrate, barbiturates, and “non-barbiturate non-benzodiazepine” drugs such as meprobamate are not recommended for the treatment of insomnia, given their significant AEs, low therapeutic index, and likelihood of tolerance and dependence.

4 . Endnotes

A. These drugs are included either on the 2012 Health Plan Employer Data and Information Set (HEDIS) list of high-risk medications in the elderly (greater than or equal to 65 years old) or in the American Geriatrics Society 2012 Beers Criteria update. [3-4]

5 . References

1. Flurazepam Prescribing Information, West-ward Pharmaceutical December 2010. 2. Schutte-Rodin S; Broch L; Buysse D; Dorsey C; Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504. 3. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2012 Feb 29. doi: 10.1111/j.1532-5415.2012.03923.x. 4. The National Committee for Quality Assurance (NCQA). Use of high-risk medications in the elderly (DAE). Available at www.ncqa.org. Accessed May 21, 2012.

Page 314 Fortamet (metformin extended-release, brand and generic), Glucophage XR (metformin extended- release, brand only) and Glumetza (metformin extended-release, brand and generic) - PA/Med Nec

Prior Authorization Guideline

GL-76932 Fortamet (metformin extended-release, brand and generic), Glucophage XR (metformin extended-release, brand only) and Glumetza (metformin extended-release, brand and generic) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 5/21/2014 P&T Revision Date: 09/18/2019 ; 10/21/2020

1 . Criteria

Product Name: Glucophage XR (brand only) or metformin extended-release (generic Fortamet*) [a, b] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - History of greater than or equal to 12 week trial [b] of metformin extended-release (generic

Page 315 Glucophage XR)

AND

2 - One of the following:

2.1 Submission of medical records (e.g. chart notes, laboratory values) documenting an inadequate response to metformin extended-release (generic Glucophage XR) as evidenced by the following:

• For patients with diabetes diagnosis, the Hemoglobin A1c level is above patients goal

2.2 Submission of medical records (e.g. chart notes, laboratory values) documenting an intolerance to metformin extended-release (generic Glucophage XR) which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction)

AND

3 - History of greater than or equal to 12 week trial [b] of metformin immediate-release

AND

4 - One of the following:

4.1 Submission of medical records (e.g. chart notes, laboratory values) documenting an inadequate response to metformin immediate-release as evidenced by the following:

• For patients with diabetes diagnosis, the Hemoglobin A1c level is above patients goal

4.2 Submission of medical records (e.g. chart notes, laboratory values) documenting an intolerance to metformin immediate-release which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction). Notes *Typically excluded from coverage. [a] State mandates may apply. Any federal regulatory requirements and the member specific benefit plan

Page 316 coverage may also impact coverage criteria. Other policies and utilizati on management programs may apply. [b] For Connecticut and Kentuck y business only a 30 day trial will be required.

Product Name: [Glumetza* or Fortamet (brand only)*] [a, b] Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Submission of article(s) published in the peer-reviewed medical literature showing that the requested drug is likely to be more efficacious to this patient than metformin extended-release (generic Glucophage XR)

AND

2 - History of greater than or equal to 12 week trial[b] of metformin extended-release (generic Glucophage XR)

AND

3 - One of the following:

3.1 Submission of medical records (e.g. chart notes, laboratory values) documenting an inadequate response to metformin extended-release (generic Glucophage XR) as evidenced by the following:

• For patients with diabetes diagnosis, the Hemoglobin A1c level is above patients goal

3.2 Submission of medical records (e.g. chart notes, laboratory values) documenting an intolerance to metformin extended-release (generic Glucophage XR) which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction).

AND

Page 317 4 - History of greater than or equal to 12 week trial[b] of metformin extended-release (generic Fortamet).

AND

5 - One of the following:

5.1 Submission of medical records (e.g. chart notes, laboratory values) documenting an inadequate response to metformin extended-release (generic Fortamet) as evidenced by the following:

• For patients with diabetes diagnosis, the Hemoglobin A1c level is above patients goal

5.2 Submission of medical records (e.g. chart notes, laboratory values) documenting an intolerance to metformin extended-release (generic Fortamet) which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction).

AND

6 - History of greater than or equal to 12 week trial[b] of metformin immediate-release

AND

7 - One of the following:

7.1 Submission of medical records (e.g. chart notes, laboratory values) documenting an inadequate response to metformin immediate-release as evidenced by the following:

• For patients with diabetes diagnosis, the Hemoglobin A1c level is above patients goal

7.2 Submission of medical records (e.g. chart notes, laboratory values) documenting an intolerance to metformin immediate-release which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction). Notes *Typically excluded from coverage. [a]State mandates may apply. Any

Page 318 federal regulatory requirements and the member specific benefit plan c overage may also impact coverage criteria. Other policies and utilizatio n management programs may apply [b]For Connecticut and Kentucky business only a 30 day trial will be required.

2 . Background

Benefit/Coverage/Program Information

Background:

According to the American Diabetes Association (ADA) metformin is the preferred initial pharmacological agent for type 2 diabetes if not contraindicated. Fortamet, Glucophage XR and Glumetza only differ in their extended-release formulation technology and excipient content. Treatment guidelines do not specify which metformin formulation should be selected for diabetes management.

This program requires a member to try metformin immediate-release (generic Glucophage) and metformin extended-release (generic Glucophage XR) prior to receiving coverage for Glucophage XR (brand only) and metformin extended-release (generic Fortamet)* and also requires an additional trial of metformin extended-release (generic Fortamet)* prior to receiving coverage for Glumetza * or Fortamet (brand only)*.

Additional Clinical Programs:

*Typically excluded from coverage.

3 . References

1. American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019: Jan; 42 (Supplement 1) 2. Glumetza [package insert]. Bridgewater, NJ: Bausch Health Companies Inc; August 2019. 3. Glucophage/Glucophage XR [package insert]. Princeton, NJ: Bristol-Myers Squibb; May 2018.

Page 319 4. Fortamet [package insert]. Ft. Lauderdale, FL: Actavis Laboratories FL, Inc; November 2018.

4 . Revision History

Date Notes

11/23/2020 Annual review. References updated.

Page 320 Glaucoma Agents - Step Therapy

Prior Authorization Guideline

GL-87050 Glaucoma Agents - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 8/17/2018 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Indications Drug Name: Vyzulta (latanoprostene) Intraocular pressure Indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

2 . Criteria

Product Name: Vyzulta* [a] Approval Length 12 month(s) Guideline Type Step Therapy

Page 321 Approval Criteria

1 - History of failure, contraindication or intolerance to latanoprost (generic Xalatan) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Vyzulta is typically excluded from coverage.

3 . Background

Benefit/Coverage/Program Information

Background: Vyzulta (latanoprostene) is an ophthalmic agent indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try latanoprost (generic Xalatan) before providing coverage for Vyzulta. Additional Clinical Rules:

4 . References

1. American Academy of Ophthalmology. Preferred Practice Pattern: Primary Open-Angle Glaucoma. September 2020. 2. Vyzulta [package insert]. Bridgewater, NJ: Bausch Health US, LLC; May 2019.

5 . Revision History

Date Notes

Page 322 5/17/2021 3/2020 P&T - Annual review. Updated references.

Page 323 GLP-1 Receptor Agonists

Prior Authorization Guideline

GL-81532 GLP-1 Receptor Agonists

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 3/1/2021 P&T Approval Date: 12/16/2020

P&T Revision Date:

1 . Indications Drug Name: Adlyxin (lixisenatide), Bydureon (exenatide extended-release), Bydureon BCise (exenatide extended-release), Byetta (exenatide), Rybelsus (semaglutide) Type 2 Diabetes Mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Drug Name: Ozempic (semaglutide), Trulicity (dulaglutide), Victoza (liraglutide) Type 2 Diabetes Mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Reduce Cardiovascular Risk Indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease

Page 324 2 . Criteria

Product Name: Adlyxin, Bydureon, Bydureon BCise, Byetta, Ozempic, Rybelsus, Trulicity, Victoza [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of type 2 diabetes mellitus

AND

2 - History of suboptimal response, contraindication or intolerance to metformin (generic Glucophage, Glucophage XR) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Adlyxin, Bydureon, Bydureon BCise, Byetta, Ozempic, Rybelsus, Trulicity, Victoza [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Page 325 3 . Background

Benefit/Coverage/Program Information

Background Adlyxin (lixisenatide), Bydureon (exenatide extended-release), Bydureon BCise (exenatide extended-release), Byetta (exenatide), Ozempic (semaglutide), Rybelsus (semaglutide), Trulicity (dulaglutide), and Victoza (liraglutide) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Ozempic, Trulicity, and Victoza are also indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class • Supply limits may be in place. • Prior Authorization/Medical Necessity may be in place

4 . References

1. Adlyxin [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; January 2019. 2. Byetta [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2020. 3. Bydureon [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2020. 4. Bydureon BCise [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2020. 5. Ozempic [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; January 2020. 6. Rybelsus [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; January 2020. 7. Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; February 2020. 8. Victoza [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; August 2020. 9. American Diabetes Association. Standard of Medical Care in Diabetes - 2020. Diabetes Care 2020;43 (Supplement 1).

5 . Revision History

Page 326 Date Notes

2/25/2021 12/2020 P&T - New program

Page 327 Glucovance

Prior Authorization Guideline

GL-32318 Glucovance

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 3/16/2001; P&T Revision Date: 10/28/2016 According to Texas State Law, all diabetic medications used for the treatment of diabetes shall be covered.

1 . Indications Drug Name: Glucovance (glyburide/metformin) Type 2 Diabetes [1-4] Indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

2 . Criteria

Product Name: Glucovance

Page 328 Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following: [1, 2]

• metformin [eg, Glucophage (metformin), Glucophage XR (metformin extended release)] • sulfonylurea [eg, Diabeta, Micronase (glyburide), Glucotrol (glipizide)]

3 . Background

Clinical Practice Guidelines

American Diabetes Association (2011) [3, 6]

Summary of antidiabetic interventions for type 2 diabetes [3] Interventions Expected Advantages Disadvantages decrease in A1C (%) Tier 1: Well-validated Core Therapies Step 1: initial therapy Lifestyle to 1 – 2 Broad benefits Insufficient for most within first decrease weight year and increase activity Metformin 1 - 2 Weight neutral GI side effects, contraindicated with renal insufficiency Step 2: additional therapy Insulin 1.5 –3.5 No dose limit, One to four injections daily, rapidly effective, monitoring, hypoglycemia, improved lipid weight gain, analogues are profile expensive Sulfonylureas 1 – 2 Rapidly effective Weight gain, hypoglycemia (especially with glibenclamide or chlorpropamide)

Tier 2: Less Well-validated Therapies TZDs 0.5 – 1.4 Improved lipid Fluid retention, CHF, weight profile gain, bone fractures, (pioglitazone), expensive, potential increase

Page 329 potential in MI (rosiglitazone) decrease in MI (pioglitazone) GLP-1 agonist 0.5 – 1.0 Weight loss Two injections daily, frequent (exenatide) GI side effects, long-term safety not established, expensive

Other drugs Alpha- 0.5 – 0.8 Weight neutral Frequent GI side effects, three Glucosidase times/ day dosing, expensive inhibitors Glinides 0.5 – 1.5† Rapidly effective Three times/day dosing, (meglitinides)† expensive, weight gain, hypoglycemia Pramlintide 0.5 – 1.0 Weight loss Three injections daily, (Symlin®) frequent GI side effects, expensive, long-term safety not established DPP-4 inhibitor 0.5 – 0.8 Weight neutral Long-term safety not (sitagliptin) established, expensive †Repaglinide is more effective at lowering A1C than nateglinide.

GI, gastrointestinal; CHF, congestive heart failure; MI, myocardial infarction

TZD (glitizones): Actos, Avandia; Alpha-glucosidase inhibitors: Precose, Glyset;

Glinides (meglitinides): Prandin, Starlix

American Association of Clinical Endocrinologists/American College of Endocrinology (2009) [5]

Page 330 tolerated, a TZD with either a GLP-1 receptor agonist or DPP-4 inhibitor may be used. Two additional second-line therapy options included in the algorithm for this A1C group only are colesevelam and AGI. These agents are included because of their minimal risk of hypoglycemia and the ability of colesevelam to lower the LDL cholesterol levels. If dual therapy fails, then triple therapy or insulin therapy should be started.

In patients with an A1C >9.0%, therapy is recommended based on the patient’s prior treatment history and whether or not symptoms are present. If the patient is asymptomatic, particularly with a relatively recent onset of diabetes, a good probability exists for preservation of some endogenous beta cell function, implying that dual therapy or triple therapy may be sufficient. In contrast, if the patient is symptomatic with polydipsia, polyuria, and weight loss, or if the patient has already been receiving treatment and regimens similar to the aforementioned ones have failed, then it is appropriate to initiate insulin therapy without delay.

4 . References

1. Glucovance Prescribing Information. Bristol-Myers Squibb Company, May 2010. 2. Metaglip Prescribing Information. Bristol-Myers Squibb Company, August 2010. 3. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32(1):193-203. 4. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract 2007;13(suppl 1):1-68. 5. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559. 6. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2010;33(suppl 1):S11-S61.

Page 331 Gonococcal Ophthalmia Neonatorum (GON) Prevention Zero Dollar Cost Share

Prior Authorization Guideline

GL-67940 Gonococcal Ophthalmia Neonatorum (GON) Prevention Zero Dollar Cost Share

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2020 P&T Approval Date: 5/17/2019 P&T Revision Date: 5/15/2020

1 . Criteria

Product Name: Erythromycin 0.5% ophthalmic ointment Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Coverage of erythromycin 0.5% ophthalmic ointment at zero dollar cost share will be approved based on one of the following criteria:

1.1 Member or health care provider intends to administer medication to newborn for the

Page 332 prophylaxis of gonococcal ophthalmia neonatorum

1.2 Newborn is 0 -1 month of age Notes Authorization will be issued for zero copay with deductible bypass for u p to 1 month from approval.

2 . Background

Benefit/Coverage/Program Information

Background

The U.S. Preventive Services Task Force (USPSTF)1 recommends prophylactic ocular topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (GON). GON can cause corneal scarring, ocular perforation, and blindness as early as 24 hours after birth. Erythromycin ophthalmic ointment is the only FDA approved drug for the prophylaxis of GON. Ocular prophylaxis of newborns is mandated in most states and is considered standard neonatal care.

This program is designed to meet Health Care Reform requirements which require coverage of 0.5% erythromycin ophthalmic ointment at zero dollar cost share if being used for primary prevention of GON.

3 . References

1. Ocular Prophylaxis for Gonococcal Ophthalmia Neonatorum. U.S. Preventive Services Task Force https://jamanetwork.com/journals/jama/fullarticle/2722778 Accessed 4/2020

4 . Revision History

Date Notes

6/19/2020 Annual review. No changes to coverage criteria.

Page 333

Page 334 Gralise, Gralise Starter Pack - Step Therapy

Prior Authorization Guideline

GL-49282 Gralise, Gralise Starter Pack - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 2/15/2019 **Guideline Effective Date: 5/1/2019**

1 . Criteria

Product Name: Gralise, Gralise Starter Pack Approval Length 12 Month Guideline Type Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to gabapentin (generic Neurontin).

Page 335

2 . Background

Benefit/Coverage/Program Information

Background:

Step Therapy programs are utilized to encourage use of lower cost alternatives for certain therapeutic classes.

This program requires a member to try gabapentin (generic Neurontin) prior to coverage of Gralise or Gralise Starter Pack.

Additional Clinical Rules:

3 . References

1. Gralise Prescribing Information. Depomed, Inc. Newark, CA. November 2017. 2. Gralise Starter Pack Prescribing Information. Depomed, Inc. Newark, CA. September 2015.

Page 336 Health Care Reform - Cardiovascular Disease Prevention Zero Cost Share

Prior Authorization Guideline

GL-85779 Health Care Reform - Cardiovascular Disease Prevention Zero Cost Share

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 3/22/2017 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Criteria

Product Name: atorvastatin (generic Lipitor) 10 mg and 20 mg and simvastatin (generic Zocor) 5 mg, 10 mg, 20 mg, 40 mg Diagnosis Coverage at zero dollar cost share Guideline Type Notification

Approval Criteria

1 - Member is between the ages of 40 and 75

Page 337 AND

2 - Medication is being used for primary prevention of CVD (i.e., member has no history of cardiovascular events)

AND

3 - Member has one or more risk factors for CVD (i.e., dyslipidemia, diabetes, hypertension, or smoking)

AND

4 - Member has a calculated 10-year risk of a cardiovascular event of 10% or greater Notes Authorization will be issued for zero copay with deductible bypass for 2 4 months. If zero dollar cost share criteria is not met the requested dru g will default to plan coverage requirements.

2 . Background

Benefit/Coverage/Program Information

Background:

The U.S. Preventive Services Task Force (USPSTF) [1] recommends that clinicians engage in shared, informed decision making with patients who are at increased risk for cardiovascular disease (CVD).

The USPSTF recommends that adults without a history of cardiovascular disease (CVD) (ie, symptomatic coronary artery disease or ischemic stroke) use a low- to moderate-dose statin for the prevention of CVD events and mortality when all of the following criteria are met: 1) they are aged 40 to 75 years; 2) they have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking); and 3) they have a calculated 10-year risk of a cardiovascular event of 10% or greater. (http://tools.acc.org/ASCVD-Risk-estimator/)

This program is designed to evaluate whether or not members meet the primary prevention criteria for obtaining coverage of low to moderate dose lipid lowering therapy (statins) at zero dollar cost share.

Additional Clinical Rules:

Page 338 • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

3 . References

1. U.S. Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/ Accessed 2/2021. 2. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(suppl 2):S1-S45. 3. Cardiovascular Risk Calculator: http://www.cvriskcalculator.com/

4 . Revision History

Date Notes

4/15/2021 Annual review. No changes.

Page 339 Healthcare Reform (HCR) Exceptions

Prior Authorization Guideline

GL-32965 Healthcare Reform (HCR) Exceptions

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 10/26/2016 The intent of this policy is to allow patients to receive medications/products that are not on the Healthcare Reform (HCR) preventative drug list (but are in the same drug class) at no cost-share. First and foremost, the patient must meet the basic HCR criteria (as described below) in order to qualify for zero cost-share.

1 . Criteria

Product Name: Contraceptives [E] Approval Length 12 Month Guideline Type Administrative

Page 340 Approval Criteria

1 - For medical necessity requests, requests to waive cost-sharing for a medication not included on a zero-cost-sharing coverage list must meet ALL of the following:

1.1 Patient is using the prescribed drug for contraception

AND

1.2 Requested product and quantity requested does not exceed the following quantities†:

• OTC female contraceptive product (with prescription) including female condoms, spermicides, or sponges – Max Day Supply = 30 • OTC emergency contraceptive (with prescription) or prescription emergency contraceptive drug (no quantity limit applies) • Contraceptive patch – (no quantity limit applies) • Contraceptive ring - (no quantity limit applies) • Injectable contraceptives – (no quantity limit applies) • Diaphragm or cervical caps – 1 unit per year • Contraceptive implant – (eligible for inclusion only if the client chooses to cover through the pharmacy benefit) • IUD – (eligible for inclusion only if the client chooses to cover through the pharmacy benefit) • Nonemergency oral contraceptives – (no quantity limit applies)

AND

1.3 If the request is for a prescription product not on the HCR preventive drug list, there must be a clinical reason why the patient cannot take two products on the HCR preventative drug list* (i.e., the patient has had an allergic reaction or intolerance to an inactive ingredient or has experienced an inadequate response) Notes †If a patient has an intolerance, allergic reaction, or an inadequate resp onse to one of the products on the HCR preventive drug list, then the q uantity limits will not apply for one time only per drug category (to allow for another product to be tried on the HCR preventive drug list).*Zero Cost Share contraceptive coverage lists are available at the Clinical Se rvices Sharepoint (http://optumrx.optum.com/sites/CST/CSDM/Shared %20Documents/Forms/AllItems.aspx?RootFolder=%2Fsites%2FCST% 2FCSDM%2FShared%20Documents%2FUMCS%20Guidelines%2FHe althcare%20Reform%20Supporting%20Document ). **FDA Contracept ive Methods available at the Clinical Services SharePoint; also see Tab le in Background Section

Product Name: Tamoxifen (applies to 20mg tablets only), Soltamox (tamoxifen solution), Evista

Page 341 (raloxifene) Approval Length 60 Months: Authorization will be issued for zero copay with deductible bypass for up to a total of 60 months (please determine if member has already received some length of therapy and if so subtract from total approval period). Guideline Type Administrative

Approval Criteria

1 - Member is greater than or equal to 35 years of age

AND

2 - Member has no prior diagnosis of any of the following:

• breast cancer • ductal carcinoma in situ (DCIS) • lobular carcinoma in situ (LCIS)

AND

3 - Member has no history of thromboembolic events (e.g.- deep venous thrombosis, pulmonary embolus, stroke or transient ischemic attack)

AND

4 - Member has an estimated 5 year risk of breast cancer based on a breast cancer risk assessment tool of greater than or equal to 3% [11]

AND

5 - One of the following:

5.1 Request is for Tamoxifen 20 mg once daily

Page 342

5.2 Both of the following:

5.2.1 Member is post-menopausal

AND

5.2.2 One of the following:

5.2.2.1 Request is for raloxifene 60 mg once daily

5.2.2.2 Request is for Evista 60 mg once daily and member has had failure, contraindication or adverse reaction to raloxifene

5.3 Both of the following:

5.3.1 Request is for Soltamox 20 mg once daily

AND

5.3.2 Member has had failure, contraindication or adverse reaction to tamoxifen tablets Notes This program is designed to meet Health Care Reform requirements w hich require coverage of tamoxifen tablets, Soltamox (tamoxifen) soluti on, or Evista (raloxifene) at zero dollar cost share if being used for prim ary prevention of breast cancer and criteria are met.

2 . Background

Clinical Practice Guidelines

Clinical Practice Guidelines **FDA Contraceptive Methods

Page 343 **FDA Contraceptives Methods

Items 6-18 pertain to the ORx standard Health Care Reform Benefit 1 – Sterilization Surgery

2 – Surgical Sterilization Implant for Women

3 – Implantable Rod*

4 – Copper IUD*

5 – IUD with Progestin* 6 – Shot/Injection

7 – OC, Combined Pill

8 – OC, Progestin Only

9 – OC, Extended/Continuous use

10 – Patch

11 – Vaginal Contraceptive Ring

12 – Diaphragm

13 – Sponge

14 – Cervical Cap

15 – Female Condom

16 – Spermicide

17 – Emergency Cont., Plan B/Plan B One-Step

18 – Emergency Cont., Ella ** FDA Contraceptive Methods, per FAQ XXVI. http://www.dol.gov/ebsa/pdf/faq-aca26.pdf

* Some plans may cover these items through the Pharmacy Benefit. Please consult the Formulary Lookup tool.

Benefit/Coverage/Program Information

Program information

Page 344 If the patient does not meet the above criteria, then the prescription will not be covered at zero cost-share.

3 . Endnotes

A. Important Risk Factors for Breast Cancer [5]: (1) Family history of breast or ovarian cancer (especially among first-degree relatives and onset before age 50 years); (2) History of atypical hyperplasia; (3) Non-malignant high-risk breast lesions; (4) Previous breast biopsy; (5) Extremely dense breast tissue; (6) Increasing age; (7) Race or ethnicity; (8) Age at menarche; (9) Age at first live childbirth; (10) Ductal carcinoma in situ (DCIS); (11) Lobular carcinoma in situ (LCIS); (12) Body mass index; (13) Menopause status or age; (14) Estrogen and progestin use; (15) Smoking; (16) Alcohol use; (17) Physical activity; (18) Diet. B. The Affordable Care Act (ACA) requires private insurers to cover certain preventive services without any patient cost-sharing (i.e., copayments) when they are delivered by a network provider. The Department of Health and Human Services (HHS) has recognized several recommending bodies (e.g., United States Preventive Services Task Force [USPSTF], Advisory Committee on Immunization Practices [ACIP] http://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/index.html, Health Resources and Services Administration [HRSA]) who have identified several medication categories that fall within the preventive health mandate. C. OptumRx has developed a Healthcare Reform Preventative Drug List posted at: http://optumrx.optum.com/sites/CST/CSDM/Shared Documents/UMCS Guidelines/Healthcare Reform Supporting Document that identifies which products are eligible for coverage without patient copayment. Some products may be excluded (such as brand oral contraceptives) unless the patient meets the criteria in this exceptions policy. D. Oral Contraceptives: In order to receive an oral contraceptive at zero cost-share, a woman must be of childbearing potential and must be requesting an oral contraceptive for contraception (and not for another use) (as well as meeting the other criteria noted at the beginning of the policy). In addition, the 21 or 28 day oral contraceptive packs should not be approved for continuous use because there are continuous use products already on the Healthcare Reform Preventative Drug List posted at: http://optumrx.optum.com/sites/CST/CSDM/Shared Documents/UMCS Guidelines/Healthcare Reform Supporting Document. E. Breast Cancer Prevention: The USPSTF recommends that clinicians engage in shared, informed decision-making with women who are at increased risk for breast cancer about medications to reduce their risk. [5] For women who are at an increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen or raloxifene. The USPSTF recommends against the routine use of medications, such as tamoxifen or raloxifene, for risk reduction of primary breast cancer in women who are not at increased risk for breast cancer. The updated STAR trial results show diminished benefits of raloxifene compared to tamoxifen after cessation of therapy, making it a preferred risk reduction choice for most post-menopausal women desiring non-surgical risk reduction therapy. However, consideration of toxicity (e.g., endometrial cancer or uterine bleeding) may still lead to the choice of raloxifene over tamoxifen in some women.

Page 345

4 . References

1. U.S. Department of Health and Human Services. Recommended Preventive Services. Available online at http://www.hhs.gov/healthcare/facts/factsheets/2010/07/preventive- services-list.html. Accessed March 20, 2014. 2. U.S. Department of Health and Human Services Health Resources and Services Administration. Women's Preventive Services: Required Health Plan Coverage Guidelines. Available online at http://www.hrsa.gov/womensguidelines/. Accessed December 30, 2016. 3. U.S. Preventive Services Task Force A and B Recommendations. Available online at http://www.uspreventiveservicestaskforce.org/uspstf/uspsabrecs.htm. Accessed May 13, 2014. 4. U.S. Preventive Services Task Force. Medications for risk reduction of primary breast cancer in women: U.S. Preventive Services Task Force recommendation statement. http://www.uspreventiveservicestaskforce.org/uspstf13/breastcanmeds/breastcanmedsrs .htm#summary. Accessed December 30, 2016. 5. Chantix Prescribing Informcation. Pfizer, Inc. October 2014. 6. Nicotrol Inhaler Prescribing Information. Pfizer, Inc. December 2008. 7. Nicotrol NS Prescribing Information. Pfizer, Inc. January 2010. 8. U.S. Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/ Accessed 11/2016 9. Assessment of Breast Cancer Risk Status. U.S. Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/uspstf13/breastcanmeds/breastcanmedsrs .htm Accessed 11/2016 10. Nolvadex (tamoxifen) Prescribing Information. AstraZeneca Pharmaceuticals Inc. Willimgton, DE. April 2013. 11. Soltamox Prescribing Information. Savient Pharmaceuticals Inc. East Brunswick, NJ. September 2012. 12. Evista Prescribing Information. Eli Lily. Indianapolis, IN. February 2015.

Page 346 High Dollar/Claim Dollar

Prior Authorization Guideline

GL-87374 High Dollar/Claim Dollar

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 3/26/2017 P&T Revision Date: 10/16/2019 ; 10/21/2020

Note:

P&T Revision Date: 10/25/2017, 12/19/2018. The intent of this policy is to serve as guidance for clients who would like to implement a High Dollar program. When a prescription exceeds the claim or high dollar threshold, the prescribed drug will be considered for coverage under the pharmacy benefit when the following criteria are met.

1 . Criteria

Product Name: A drug (non-anti-cancer chemotherapeutic regimen) used for an off-label indication or non-FDA approved indication Approval Length 12 months, if no PA is on file. Approval duration is granted for length of current PA on file (if existing PA is on file). Guideline Type Administrative

Page 347

Approval Criteria

1 - One of the following:

1.1 Medication is being prescribed for an FDA-approved indication

1.2 One of the following:

1.2.1 Diagnosis is supported as a use in American Hospital Formulary Service Drug Information (AHFS DI) [1]

1.2.2 Diagnosis is supported in the FDA Uses/Non-FDA Uses section in DRUGDEX Evaluation with a Strength of Recommendation rating of IIb or better (see DRUGDEX Strength of Recommendation table in Background section) [1]

1.2.3 The use is supported by clinical research in two articles from major peer reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer-reviewed medical journal**

AND

2 - One of the following:

2.1 The dosage quantity/duration of the medication is reasonably safe and effective based on information contained in the FDA approved labeling, peer-reviewed medical literature, or accepted standards of medical practice

2.2 The dosage/quantity/duration of the medication is reasonably safe and effective based on

Page 348 one of the following compendia:

• American Hospital Formulary Service (AHFS) Compendium • Thomson Reuters (Healthcare) Micromedex/DrugDex (not Drug Points) Compendium • Elsevier Gold Standard’s Clinical Pharmacology Compendium • National Comprehensive Cancer Network Drugs and Biologics Compendium

Notes **May not apply to all benefit plans.

Product Name: A drug or biological in an anti-cancer chemotherapeutic regimen Approval Length 12 months, if no PA is on file. Approval duration is granted for length of current PA on file (if existing PA is on file). Guideline Type Administrative

Approval Criteria

1 - One of the following:

1.1 Medication is being prescribed for an FDA-approved indication

1.2 One of the following:

1.2.1 Diagnosis is supported as a use in American Hospital Formulary Service Drug Information (AHFS DI) [2]

1.2.3 Diagnosis is supported as a use in the National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium with a Category of Evidence and Consensus of 1, 2A, or 2B (see NCCN Categories of Evidence and Consensus table in Background section) [2, B]

Page 349

1.2.4 Diagnosis is supported as an indication in Clinical Pharmacology [2]

1.2.5 Off-label use is supported in one of the published, peer-reviewed medical literature listed below: [2, C]

• American Journal of Medicine • Annals of Internal Medicine • Annals of Oncology • Annals of Surgical Oncology • Biology of Blood and Marrow Transplantation • Blood • Bone Marrow Transplantation • British Journal of Cancer • British Journal of Hematology • British Medical Journal • Cancer • Clinical Cancer Research • Drugs • European Journal of Cancer (formerly the European Journal of Cancer and Clinical Oncology) • Gynecologic Oncology • International Journal of Radiation, Oncology, Biology, and Physics • The Journal of the American Medical Association • Journal of Clinical Oncology • Journal of the National Cancer Institute • Journal of the National Comprehensive Cancer Network (NCCN) • Journal of Urology • Lancet • Lancet Oncology • Leukemia • The New England Journal of Medicine • Radiation Oncology

1.2.6 Diagnosis is supported as a use in Wolters Kluwer Lexi-Drugs rated as "Evidence Level A" with a "Strong" recommendation. (see Lexi-Drugs Strength of Recommendation table in Background section) [2, 4, 5]

Page 350

AND

2 - One of the following:

2.2 The dosage/quantity/duration of the medication is reasonably safe and effective based on one of the following compendia:

Notes **May not apply to all benefit plans.

2 . Background

Clinical Practice Guidelines

DRUGDEX Strength of Recommendation [5]

Class Recommendation Description

Class I Recommended The given test or treatment has been proven useful, and should be performed or administered.

Class IIa Recommended, In The given test or treatment Most Cases is generally considered to be useful, and is indicated in most cases.

Class IIb Recommended, in The given test or treatment Some Cases may be useful, and is

Page 351 indicated in some, but not most, cases.

Class III Not The given test or treatment Recommended is not useful, and should be avoided

Class Evidence Indeterminate Inconclusive

NCCN Categories of Evidence and Consensus [B]

Category Level of Consensus

1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

Lexi-Drugs: Strength of Recommendation for Inclusion in Lexi-Drugs for Oncology Off- Label Use and Level of Evidence Scale for Oncology Off-Label Use [5]

Strength of Recommendation for Inclusion

Strong (for proposed The evidence persuasively off-label use) supports the off-label use (ie, Level of Evidence A). Equivocal (for The evidence to support the proposed off-label off-label use is of uncertain use) clinical significance (ie, Level of Evidence B, C). Additional studies may be necessary to further define the role of this medication for the off-label use. Against proposed off- The evidence either advocates label use against the off-label use or suggests a lack of support for the off-label use (independent of Level of Evidence). Additional studies are

Page 352 necessary to define the role of this medication for the off-label use.

Level of Evidence Scale for Oncology Off-Label Use

A Consistent evidence from well-performed randomized, controlled trials or overwhelming evidence of some other form (eg, results of the introduction of penicillin treatment) to support off-label use. Further research is unlikely to change confidence in the estimate of benefit. B Evidence from randomized, controlled trials with important limitations (eg, inconsistent results, methodologic flaws, indirect, imprecise); or very strong evidence of some other research design. Further research (if performed) is likely to have an impact on confidence in the estimate of benefit and risk and may change the estimate. C Evidence from observational studies (eg, retrospective case series/reports providing significant impact on patient care); unsystematic clinical experience; or potentially flawed randomized, controlled trials (eg, when limited options exist for condition). Any estimate of effect is uncertain. G Use has been substantiated by inclusion in at least one evidence-based or consensus-based clinical practice guideline.

3 . Endnotes

A. OptumRx has high dollar criteria for clients who opt for such a program to help manage prescription costs. If the prescription cost exceeds the claim or high dollar threshold, then an administrative PA will be required. The pharmacist will review the prescription to see if it is in-line with FDA approved labeling or well supported by the approved compendia or a peer-reviewed medical journal. B. NCCN Categories of Evidence and Consensus. Category 1: The recommendation is based on high-level evidence (i.e., high-powered randomized clinical trials or meta- analyses), and the NCCN Guideline Panel has reached uniform consensus that the recommendation is indicated. In this context, uniform means near unanimous positive support with some possible neutral positions. Category 2A: The recommendation is based on lower level evidence, but despite the absence of higher level studies, there is uniform consensus that the recommendation is appropriate. Lower level evidence is interpreted broadly, and runs the gamut from phase II to large cohort studies to case series to individual practitioner experience. Importantly, in many instances, the retrospective studies are derived from clinical experience of treating large numbers of

Page 353 patients at a member institution, so NCCN Guideline Panel Members have first-hand knowledge of the data. Inevitably, some recommendations must address clinical situations for which limited or no data exist. In these instances the congruence of experience-based judgments provides an informed if not confirmed direction for optimizing patient care. These recommendations carry the implicit recognition that they may be superseded as higher level evidence becomes available or as outcomes-based information becomes more prevalent. Category 2B: The recommendation is based on lower level evidence, and there is nonuniform consensus that the recommendation should be made. In these instances, because the evidence is not conclusive, institutions take different approaches to the management of a particular clinical scenario. This nonuniform consensus does not represent a major disagreement, rather it recognizes that given imperfect information, institutions may adopt different approaches. A Category 2B designation should signal to the user that more than one approach can be inferred from the existing data. Category 3: Including the recommendation has engendered a major disagreement among the NCCN Guideline Panel Members. The level of evidence is not pertinent in this category, because experts can disagree about the significance of high level trials. Several circumstances can cause major disagreements. For example, if substantial data exist about two interventions but they have never been directly compared in a randomized trial, adherents to one set of data may not accept the interpretation of the other side's results. Another situation resulting in a Category 3 designation is when experts disagree about how trial data can be generalized. An example of this is the recommendation for internal mammary node radiation in postmastectomy radiation therapy. One side believed that because the randomized studies included this modality, it must be included in the recommendation. The other side believed, based on the documented additional morbidity and the role of internal mammary radiation therapy in other studies, that this was not necessary. A Category 3 designation alerts users to a major interpretation issue in the data and directs them to the manuscript for an explanation of the controversy. [3] C. Abstracts (including meeting abstracts) are excluded from consideration. When evaluating peer-reviewed medical literature, the following (among other things) should be considered: 1) Whether the clinical characteristics of the beneficiary and the cancer are adequately represented in the published evidence 2) Whether the administered chemotherapy regimen is adequately represented in the published evidence. 3) Whether the reported study outcomes represent clinically meaningful outcomes experienced by patients. 4) Whether the study is appropriate to address the clinical question. The following should be considered: a) Whether the experimental design, in light of the drugs and conditions under investigation, is appropriate to address the investigative question. (For example, in some clinical studies, it may be unnecessary or not feasible to use randomization, double blind trials, placebos, or crossover.); b) That non-randomized clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of drugs; and c) That case reports are generally considered uncontrolled and anecdotal information and do not provide adequate supportive clinical evidence for determining accepted uses of drugs. [2]

4 . References

1. Center for Medicaid & Medicare Services. Medicare Prescription Drug Benefit Manual. Chapter 6 – Part D Drugs and Formulary Requirements. Section 10.6. Available at:

Page 354 https://www.cms.gov/Medicare/Prescription-Drug- Coverage/PrescriptionDrugCovContra/Downloads/Part-D-Benefits-Manual-Chapter- 6.pdf. Accessed September 29, 2020. 2. Center for Medicaid & Medicare Services. Medicare Benefit Policy Manual. Chapter 15 - Covered Medical and Other Health Services. Section 50.4.5. Available at: https://www.cms.gov/Regulations-and- Guidance/Guidance/Manuals/downloads/bp102c15.pdf. Accessed September 29, 2020. 3. National Comprehensive Cancer Network Categories of Evidence and Consensus. Available at: https://www.nccn.org/professionals/physician_gls/categories_of_consensus.aspx. Accessed September 29, 2020. 4. Center for Medicaid & Medicare Services. Medicare Benefit Policy Manual. Wolters Kluwer Clinical Drug Information Lexi-Drugs Compendium Revision Request - CAG- 00443O. Available at: https://www.cms.gov/medicare-coverage- database/details/medicare-coverage-document-details.aspx?MCDId=31#decision. Accessed September 29, 2020. 5. Wolters Kluwer Clinical Drug Information’s Request for CMS evaluation of Lexi-Drugs as a compendium for use in the determination of medically-accepted indications of drugs/biologicals used off-label in anti-cancer chemotherapeutic regimens. Available at: https://www.cms.gov/Medicare/Coverage/CoverageGenInfo/downloads/covdoc31.pdf. Accessed September 29, 2020. 6. Micromedex Healthcare Series. Recommendation, Evidence and Eddicacy Ratings. https://www.micromedexsolutions.com/micromedex2/librarian/ssl/true/CS/6E0ED9/ND_P R/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/8B9F5B/ND_PG/evi dencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/P FActionId/evidencexpert.IntermediateToDocumentLink?docId=3198&contentSetId=50. Accessed September 29, 2020.

5 . Revision History

Date Notes

5/20/2021 Addition of EHB formulary to guideline, no changes to criteria

Page 355 HIV Pre-exposure Prophylaxis (PrEP) Zero Dollar Cost Share – California – Descovy and generic tenofovir disoproxil fumarate 300 mg

Prior Authorization Guideline

GL-81338 HIV Pre-exposure Prophylaxis (PrEP) Zero Dollar Cost Share – California – Descovy and generic tenofovir disoproxil fumarate 300 mg

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 1/1/2021 P&T Approval Date: 12/16/2020

P&T Revision Date:

1 . Criteria

Product Name: Descovy, generic tenofovir disoproxil fumarate 300 mg Diagnosis Pre-Exposure Prophylaxis (PrEP) Approval Length Authorization will be issued for zero copay with deductible bypass for 12 months Guideline Type Notification

Approval Criteria

Page 356 1 - Preventive care coverage for pre-exposure prophylaxis (PrEP) is being requested for either Descovy or tenofovir 300 mg

2 . Background

Benefit/Coverage/Program Information

Background:

California regulations require the use of HIV medications for Pre-Exposure Prophylaxis to be covered at zero dollar cost share upon request.

Additional Clinical Rules:

3 . References

1. U.S. Preventive Services Task Force Final Recommendation Statement Prevention of Human Immunodeficiency Virus (HIV) Infection: Pre-exposure Prophylaxis https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationState mentFinal/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure- prophylaxis#consider Accessed August 7, 2020 2. US Public Health Service Pre-exposure Prophylaxis For The Prevention Of HIV Infection In The United States – 2017 Update – A Clinical Practice Guideline https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf Accessed August 7, 2020

4 . Revision History

Date Notes

2/18/2021 Added SP lookup to guideline per PA request due to Descovy PAS flag moving to Specialty. STD lookup remains as tenofovir will keep its Sta ndard PAS flag.

Page 357 HIV Pre-exposure Prophylaxis (PrEP) Zero Dollar Cost Share – generic tenofovir disoproxil fumarate 300 mg

Prior Authorization Guideline

GL-74177 HIV Pre-exposure Prophylaxis (PrEP) Zero Dollar Cost Share – generic tenofovir disoproxil fumarate 300 mg

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 11/15/2019 P&T Revision Date: 9/16/2020

1 . Criteria

Product Name: generic tenofovir disoproxil fumarate 300mg Approval Length 12 month(s) Guideline Type Notification

Approval Criteria

1 - Coverage at zero dollar cost share will be approved based on both of the following criteria:

1.1 Member is taking generic tenofovir disoproxil fumarate 300 mg as effective antiretroviral

Page 358 therapy for PrEP

AND

1.2 Generic tenofovir disoproxil fumarate 300 mg will be used as part of a comprehensive prevention strategy including other prevention measures Notes Authorization will be issued for zero copay with deductible bypass for 1 2 months. If zero dollar cost share criteria are not met the requested dr ug will default to standard plan coverage.

2 . Background

Benefit/Coverage/Program Information

Background: The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians offer preexposure prophylaxis (PrEP) with effective antiretroviral therapy to persons who are at high risk of HIV acquisition.1

Once-daily oral treatment with Truvada® (emtricitabine/tenofovir disoproxil fumarate) is approved by the US Food and Drug Administration (FDA) for use as PrEP in persons at risk of sexual acquisition of HIV infection. Several studies reviewed by the USPSTF found that tenofovir disoproxil fumarate alone was also effective as PrEP and CDC guidelines note that, given these trial data, tenofovir disoproxil fumarate alone can be considered as an alternative regimen for high-risk heterosexually active men and women and persons who inject drugs.1-3

This program is designed to meet Health Care Reform requirements which require coverage of effective antiretroviral therapy, which includes tenofovir disoproxil fumarate, at zero dollar cost share if being used for PrEP and criteria are met.

Additional Clinical Rules:

3 . References

Page 359 1. U.S. Preventive Services Task Force Final Recommendation Statement Prevention of Human Immunodeficiency Virus (HIV) Infection: Pre-exposure Prophylaxis https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationState mentFinal/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure- prophylaxis#consider Accessed August 7, 2020. 2. US Public Health Service Pre-exposure Prophylaxis For The Prevention Of HIV Infection In The United States – 2017 Update – A Clinical Practice Guideline https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf Accessed August 7, 2020. 3. Truvada Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2020.

4 . Revision History

Date Notes

9/28/2020 Removed brand Truvada as this is a non HCR drug.

Page 360 Impavido (miltefosine)

Prior Authorization Guideline

GL-85719 Impavido (miltefosine)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 6/22/2016 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Indications Drug Name: Impavido (miltefosine) Leishmaniasis Indicated in adults and adolescents greater than or equal to 12 years of age and weighing greater than or equal to 30 kg (66 lbs) for treatment of visceral leishmaniasis due to Leishmania donovani, cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis, and mucosal leishmaniasis due to Leishmania braziliensis. The efficacy of Impavido in the treatment of other Leishmania species has not been evaluated.

2 . Criteria

Product Name: Impavido Approval Length 28 Day(s)

Page 361 Guideline Type Notification

Approval Criteria

1 - Diagnosis of one of the following:

• Visceral leishmaniasis due to Leishmania donovani • Cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, or Leishmania panamensis • Mucosal leishmaniasis due to Leishmania braziliensis • Primary Amebic Meningoencephalitis (PAM) [Off Label] • Keratitis due to Acanthamoeba [Off label] • Amebic encephalitis due to Balamuthia mandrillaris [Off Label]

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Background:

Impavido (miltefosine) is an antileishmanial agent indicated in adults and adolescents ≥12 years of age and weighing ≥30 kg (66 lbs) for treatment of visceral leishmaniasis due to Leishmania donovani, cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis, and mucosal leishmaniasis due to Leishmania braziliensis. The efficacy of Impavido in the treatment of other Leishmania species has not been evaluated. Impavido should be administered as a dose of one 50 mg capsule two to three times daily for 28 consecutive days.

4 . References

1. Impavido (prescribing information). Orlando FL: Profounda, Inc.: June 2019.

Page 362 2. CDC Guidelines. Naegleria fowleri – Primary Amebic Meningoencephalitis (PAM) – Amebic Encephalitis. http://www.cdc.gov/parasites/naegleria/index.html. Accessed January 2020. 3. CDC Guidelines. Parasites – Acanthamoeba - Granulomatous Amebic Encephalitis (GAE); Keratitis. https://www.cdc.gov/parasites/acanthamoeba/index.html. Accessed January 2020. 4. CDC Guidelines. Balamuthia mandrillaris - Granulomatous Amebic Encephalitis (GAE). https://www.cdc.gov/parasites/balamuthia/index.html. Accessed January 2020.

5 . Revision History

Date Notes

4/14/2021 Annual review. No changes.

Page 363 Ingrezza (valbenazine) - PA/Med Nec

Prior Authorization Guideline

GL-58251 Ingrezza (valbenazine) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2020 P&T Approval Date: 11/17/2017 P&T Revision Date: 11/15/2019

Note:

P&T Approval Date: 11/17/2017; P&T Revision Date: 11/16/2018, 11/15/2019; **Effective Date: 2/1/2020**

1 . Indications Drug Name: Ingrezza (valbenazine) Tardive dyskinesia Indicated for the treatment of adults with tardive dyskinesia.

2 . Criteria

Product Name: Ingrezza [a]

Page 364 Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe tardive dyskinesia

AND

2 - One of the following:

• Patient has persistent symptoms of tardive dyskinesia despite a trial of dose reduction, tapering, or discontinuation of the offending medication • Patient is not a candidate for a trial of dose reduction, tapering, or discontinuation of the offending medication

AND

3 - One of the following

3.1 History of failure, contraindication, or intolerance to Austedo (deutetrabenazine)

3.2 Both of the following:

3.2.1 Patient is currently on Ingrezza therapy

AND

3.2.2 Patient has not received a manufacturer supplied sample at no cost in the prescriber's office, or any form of assistance from the Neurocrine Biosciences sponsored Inbrace program (e.g., sample card which can be redeemed at a pharmacy for a free supply of medication) as a means to establish as a current user of Ingrezza*

Page 365 AND

4 - Prescribed by or in consultation with one of the following:

• Neurologist • Psychiatrist

Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. *Patients requesting initial authorization who were established on the rapy via the receipt of a manufacturer supplied sample at no cost in the prescriber’s office or any form of assistance from the Neurocrine Biosc iences sponsored Inbrace program shall be required to meet initial auth orization criteria as if patient were new to therapy.

Product Name: Ingrezza [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Ingrezza therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

Ingrezza is a vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the treatment of adults with tardive dyskinesia.

Additional Clinical Rules:

Page 366 Supply limits may be in place

4 . References

1. Ingrezza Prescribing Information, Neurocrine Biosciences, Inc. July 2019. 2. Hauser RA, Factor SA, Marder SR, et al. Kinect 3: A phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. American Journal of Psychiatry. May 2017. 174:5. 3. Waln O, Jankovic J: An update on tardive dyskinesia: from phenomenology treatment. Tremor Other Hyperkinet Mov (N Y) 2013; 3: tre-03-161-4138-1.

5 . Revision History

Date Notes

12/23/2019 Annual review. No changes to clinical coverage criteria. Updated refer ence.

Page 367 Inhaled Corticosteroids

Prior Authorization Guideline

GL-81239 Inhaled Corticosteroids

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 2/18/2015 P&T Revision Date: 03/18/2020 ; 10/21/2020 ; 3/17/2021

1 . Indications Drug Name: Alvesco (ciclesonide) Inhalation Aerosol Asthma Indicated for the maintenance treatment of asthma as prophylactic therapy in adult and adolescent patients 12 years of age and older. Important Limitations of Use: Alvesco is NOT indicated for the relief of acute bronchospasm or for children under 12 years of age.

Drug Name: ArmonAir RespiClick (fluticasone propionate) Inhalation Powder Asthma Indicated for the maintenance treatment of asthma as prophylactic therapy in patients 12 years of age and older. Important Limitation of Use: ArmonAir RespiClick is not indicated for the relief of acute bronchospasm or for children under 12 years of age.

Drug Name: Asmanex HFA (mometasone furoate) Inhalation Aerosol Asthma Indicated for the maintenance treatment of asthma as prophylactic therapy in patients 12 years of age and older. Important Limitations of Use: Asmanex HFA is NOT indicated for the relief of acute bronchospasm.

Page 368 Drug Name: Asmanex Twisthaler (mometasone furoate) Inhalation Powder Asthma Indicated for the maintenance treatment of asthma as prophylactic therapy in patients 4 years of age and older. Important Limitations of Use: Asmanex Twisthaler is NOT indicated for the relief of acute bronchospasm or in children less than 4 years of age.

Drug Name: Armonair Asthma Indicated for the maintenance treatment of asthma as prophylactic therapy in patients 12 years of age and older.

2 . Criteria

Product Name: Armonair Digihaler*, Alvesco*, ArmonAir RespiClick*, Asmanex HFA*, Asmanex Twisthaler* Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - Trial and failure, contraindication, or intolerance to two of the following preferred brands:

• Arnuity Ellipta • Flovent Diskus or Flovent HFA • Pulmicort Flexhaler • QVAR/QVAR Redihaler

Notes *Product may be excluded depending on the plan.

3 . References

1. Alvesco Prescribing Information. Covis Pharma, Zug 6300, Switzerland. March 2018. 2. ArmonAir RespiClick Prescribing Information. Teva Respiratory, LLC. Waterford, IE. September 2020. 3. Asmanex Prescribing Information. Merck & Co. Inc. Whitehouse Station, NJ. August 2019. 4. Asmanex HFA Prescribing Information. Merck & Co. Inc. Whitehouse Station, NJ. August 2019. 5. Armonair Prescribing Information. Teva Pharmaceuticals. Parsippany, NJ. September 2020.

Page 369

4 . Revision History

Date Notes

2/22/2021 Annual review

Page 370 Invokana (canagliflozin) - NonFormulary

Prior Authorization Guideline

GL-88424 Invokana (canagliflozin) - NonFormulary

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 5/15/2020 P&T Revision Date: 5/21/2021

1 . Indications Drug Name: Invokana (canagliflozin) Type 2 diabetes mellitus. Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Type 2 diabetes mellitus. indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD), and to reduce the risk of end- stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria > 300 mg/day.

2 . Criteria

Page 371 Product Name: Invokana (canagliflozin) Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Non Formulary

Approval Criteria

1 - Invokana will be approved based on all the following criteria:

1.1 Diagnosis of type 2 diabetes mellitus

AND

1.2 Diagnosis of diabetic nephropathy with albuminuria > 300 mg/day

AND

1.3 Provider attests that Jardiance isn’t a suitable treatment option

AND

1.4 Submission of medical records (laboratory and clinical documentation) confirming diagnosis of kidney disease

Product Name: Invokana (canagliflozin) Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Non Formulary

Approval Criteria

1 - Invokana will be approved based on the following criterion:

1.1 Documentation of a positive clinical response to Invokana therapy

Page 372

3 . Background

Benefit/Coverage/Program Information

Background:

Farxiga (dapagliflozin)*, Invokana (canagliflozin)*, Jardiance (empagliflozin) and Steglatro (ertugliflozin)* are sodium-glucose co-transporter 2 (SGLT2) inhibitors indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Farxiga*, Invokana* and Jardiance have additional indications. Farxiga* is indicated to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD) or multiple cardiovascular (CV) risk factors and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction. Invokana* is indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD), and to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria > 300 mg/day. Jardiance is indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

3. Additional Clinical Rules:

4 . References

1. Jardiance [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2020. 2. Invokana [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; August 2020. 3. Farxiga [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP.; May 2020. 4. Steglatro [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; March 2020. 5. American Diabetes Association. Standard of Medical Care in Diabetes- 2020. Diabetes Care 2021;44 (Supplement 1)

Page 373 5 . Revision History

Date Notes

6/15/2021 Annual review. Updated background section and references.

Page 374 Iron Chelators

Prior Authorization Guideline

GL-90467 Iron Chelators

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 1/1/2012 P&T Revision Date: 09/18/2019 ; 09/16/2020 ; 6/16/2021

1 . Indications Drug Name: Exjade (deferasirox), Jadenu (deferasirox) Chronic iron overload due to blood transfusions Indicated for the treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older. The safety and efficacy of Exjade and Jadenu, when administered with other iron chelation therapy, have not been established. It is recommended that therapy with Exjade or Jadenu be started when a patient has evidence of chronic iron overload, such as the transfusion of approximately 100 mL/kg of packed red blood cells (approximately 20 units for a 40-kg patient) and a serum ferritin consistently greater than 1000 mcg/L.

Chronic iron overload due to non-transfusion dependent thalassemia syndromes Indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion dependent thalassemia (NTDT) syndromes and with a liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L. This indication is based on achievement of an LIC less than 5 mg Fe/g dw.

Drug Name: Ferriprox (deferiprone) tablet and oral solution

Page 375 Transfusional iron overload Indicated for the treatment of transfusional iron overload in adult and pediatric patients with thalassemia syndromes, sickle cell disease or other anemias. Ferriprox Tablets are indicated in patients 8 years of age and older, and Ferriprox Oral Solution is indicated in patients 3 years of age and older. Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or in patients with Diamond Blackfan anemia.

2 . Criteria

Product Name: Exjade, Jadenu Diagnosis Chronic Iron Overload Due to Blood Transfusions (i.e., Transfusional Iron Overload) Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - Diagnosis of chronic iron overload (e.g., sickle cell anemia, thalassemia, etc.) due to blood transfusion

Product Name: Exjade, Jadenu Diagnosis Chronic Iron Overload Due to Blood Transfusions (i.e., Transfusional Iron Overload) Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Exjade or Jadenu therapy

Product Name: Ferriprox tablet, Ferriprox oral solution Diagnosis Chronic Iron Overload Due to Blood Transfusions (i.e., Transfusional

Page 376 Iron Overload) Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - Diagnosis of transfusional iron overload due to thalassemia syndromes, sickle cell disease, or other anemias

AND

2 - Ferriprox will not be used for the treatment of transfusional iron overload due to myelodysplastic syndrome or Diamond Blackfan anemia.

Product Name: Ferriprox tablet, Ferriprox oral solution Diagnosis Chronic Iron Overload Due to Blood Transfusions (i.e., Transfusional Iron Overload) Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Ferriprox therapy

Product Name: Exjade, Jadenu Diagnosis Chronic Iron Overload in Non-Transfusion Dependent Thalassemia Syndromes Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

Page 377

1 - Diagnosis of chronic iron overload in non-transfusion dependent thalassemia (NTDT) syndrome

AND

2 - Patient has liver iron (Fe) concentration (LIC) levels consistently greater than or equal to 5 mg Fe per gram of dry weight prior to initiation of treatment with Exjade or Jadenu

AND

3 - Patient has serum ferritin levels consistently greater than 300 mcg/L prior to initiation of treatment with Exjade or Jadenu

Product Name: Exjade, Jadenu Diagnosis Chronic Iron Overload in Non-Transfusion Dependent Thalassemia Syndromes Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Exjade or Jadenu therapy

3 . Background

Benefit/Coverage/Program Information

Background: Exjade® (deferasirox) and Jadenu® (deferasirox) are iron chelating agents indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. The safety and efficacy of Exjade and Jadenu, when administered with other iron chelation therapy, have not been established. It is recommended that therapy with Exjade or Jadenu be started when a patient has evidence of chronic transfusional iron overload, such as the transfusion of approximately 100 mL/kg of packed red

Page 378 blood cells (approximately 20 units for a 40-kg patient) and a serum ferritin consistently >1000 mcg/L.

Exjade and Jadenu are also indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion dependent thalassemia (NTDT) syndromes and with a liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L. This indication is based on achievement of an LIC less than 5 mg Fe/g dw.

Ferriprox® (deferiprone) is an iron chelator indicated for the treatment of transfusional iron overload in adult and pediatric patients with thalassemia syndromes, sickle cell disease or other anemias.

Ferriprox Tablets are indicated in patients ≥ 8 years of age and Ferriprox Oral Solution is indicated in patients ≥ 3 years of age. Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or in patients with Diamond Blackfan anemia.

Additional Clinical Rules:

4 . References

1. Exjade [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2020. 2. Ferriprox Tablets [package insert]. Toronto, Ontario, Canada: Apotex Inc.; April 2021. 3. Ferriprox Oral Solution [package insert]. Toronto, Ontario, Canada: Apotex Inc.; April 2021. 4. Jadenu [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2020.

5 . Revision History

Page 379 Date Notes

8/1/2021 Updated coverage criteria for Ferriprox per changes to the FDA approv ed label. Updated background and references.

Page 380 Kapvay (clonidine) extended-release

Prior Authorization Guideline

GL-31727 Kapvay (clonidine) extended-release

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 4/5/2011; P&T Revision Date: 7/27/2016

1 . Indications Drug Name: Kapvay (clonidine) extended-release Attention Deficit Hyperactivity Disorder (ADHD) Indicated for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications.

2 . Criteria

Product Name: Brand Kapvay or generic clonidine extended-release

Page 381 Guideline Type Step Therapy

Approval Criteria

1 - History of two of the following generics or preferred brands:

• amphetamine-dextroamphetamine IR • dexmethylphenidate IR • dextroamphetamine IR • methylphenidate IR or ER • Vyvanse • Adderall XR

3 . References

1. Kapvay Prescribing Information. Shionogi Pharma, April 2016.

Page 382 Ketek (Telithromycin)

Prior Authorization Guideline

GL-6131 Ketek (Telithromycin)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 2/20/2007; CPS Revision Date: 8/21/2012

1 . Indications Drug Name: Ketek (telithromycin) [1, A] Community-acquired pneumonia Is indicated for the treatment of community-acquired pneumonia (of mild to moderate severity) due to Streptococcus pneumoniae, (including multi- drug resistant isolates [MDRSP*]), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae, for patients 18 years and above. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ketek and other antibacterial drugs, Ketek should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. *MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae),

Page 383 and are isolates resistant to two or more of the following antibiotics: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

2 . Criteria

Product Name: Ketek Approval Length 10 Day Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of community-acquired pneumonia in an adult outpatient [1, 2, 3, 9]

AND

2 - All of the following: [2, 3, 9, A]

2.1 History of failure, intolerance, or resistance to one of the following advanced-generation macrolides:

• azithromycin (eg, Zithromax, Zmax) • clarithromycin (eg, Biaxin, Biaxin XL)

AND

2.2 History of failure, intolerance, or resistance to doxycycline (eg, Vibramycin, Adoxa, Doryx)

AND

2.3 History of failure, intolerance, or resistance to Levaquin (levofloxacin)

3 . Background

Page 384 Clinical Practice Guidelines

Infectious Disease Society of America / American Thoracic Society (2007) [9]

For outpatient treatment, patients previously healthy with no risk factors for drug-resistant S. pneumoniae (DRSP) infection, a macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; level I evidence) and doxycycline (weak recommendation; level III evidence) were recommended. In the presence of comorbidities (such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; use of antimicrobials within the previous 3 months [in which case an alternative from a different class should be selected]; or other risks for DRSP infection), a respiratory fluoroquinolone (strong recommendation; level I evidence) and a beta-lactam plus a macrolide (strong recommendation; level I evidence) (High- dose amoxicillin [e.g.,1 g 3 times daily] or amoxicillin-clavulanate [2 g 2 times daily] is preferred; alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg 2 times daily]; doxycycline [level II evidence] is an alternative to the macrolide) are recommended. In regions with a high rate (125%) of infection with high level macrolide resistant S. pneumonia (MIC 16 mg/mL), the use of alternative agents listed for patients with or without comorbidities maybe considered (moderate recommendation; level III evidence).

Infectious Diseases Society of America (2003) [2, 8]

Appropriate initial empiric therapy for suspected bacterial CAP in immunocompetent outpatients who were previously healthy with no recent antibiotic therapy would include a macrolide or doxycycline. Those with recent antibiotic therapy should receive a respiratory fluoroquinolone alone, an advanced macrolide plus high-dose amoxicillin, or an advanced macrolide plus high-dose amoxicillin-clavulanate.

American Thoracic Society (2001) [3, 8]

If the patient has no cardiopulmonary disease, and no risks for DRSP, aspiration, or enteric gramnegatives, then the likely organisms will be pneumococcus, atypical pathogens, respiratory viruses, and possibly H. influenzae (especially in cigarette smokers). For these therapy should be with an advanced generation macrolide, with doxycycline as a second choice (because of less reliable activity against pneumococcus) for patients who are allergic or intolerant of macrolides. The committee felt that broader spectrum coverage with a new antipneumococcal fluoroquinolone would be effective, but unnecessary, and if used in this setting could promote overusage of this valuable class of antibiotics (Level III evidence). If H. influenzae is not likely, because the patient is a nonsmoker without cardiopulmonary disease, any macrolide could be used, including erythromycin. However, the advanced generation macrolides (azithromycin, clarithromycin) have a lower incidence of gastrointestinal side

Page 385 effects than erythromycin and are administered less frequently (once or twice daily) than erythromycin, improving the likelihood of patient compliance with therapy. Although clarithromycin is not as active in vitroagainst H. influenzae as azithromycin, clinical experience with both azithromycin and clarithromycin in CAP has been favorable. This may be explained by the excellent concentrations of macrolides achieved in the epithelilal lining fluid and alveolar macrophages, and by the predominance of the efflux mechanism of pneumococcal resistance in North America.

The more complex outpatient (Group II, Table 3) can be managed with either a beta-lactam/macrolide combination or monotherapy with an antipneumococcal fluoroquinolone (Level II evidence). Doxycycline can be used, along with a beta- lactam, as an alternative to a macrolide for these patients.

4 . Endnotes

A. Numerous national societies have published their recommendations for the management of CAP. This review article looked at the latest guidelines from two leading organizations – the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). Using a composite of both guidelines, the treatment regimens for outpatient CAP can be simplified as follows: Monotherapy with either a beta-lactam, a macrolide antibiotic, doxycycline, or a fluoroquinolone antibiotic is sufficient. [8] B. Because of numerous safety issues including hepatotoxicity, visual disorders, loss of consciousness, and myasthenia gravis, the FDA Anti-Infective Drugs Advisory Committee voted against continued marketing of telithromycin for ABECB (acute bacterial exacerbation of chronic bronchitis) and ABS (acute bacterial sinusitis). The FDA chose to enforce this decision on February 12, 2007.

5 . References

1. Ketek Prescribing Information. Sanofi-Aventis, December 2010. 2. Mandell L, Bartlett J, Dowell S, File T, Musher D, Whitney C. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003;37:1405-33. 3. American Thoracic Society. Guidelines for the management of adults with community- acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001;163:1730-1754. 4. Brook I, Gooch W, Reiner S, et al. Medical management of acute bacterial sinusitis. Recommendations of a clinical advisory committee on pediatric and adult sinusitis. Ann Otol Rhinol Laryngol 2000;109:1-20. 5. Balter M, Forge J, Low D, et al. Canadian guidelines for the management of acute exacerbations of chronic bronchitis. Can Respir J 2003;10:3B-32B. 6. Brunton S, Carmichael B, Colgan R, et al. Acute exacerbation of chronic bronchitis: a primary care consensus guideline. Am J Manag Care 2004;10:689-696.

Page 386 7. Gilbert, DN, et al. The Sanford Guide to Antimicrobial Therapy. Hyde Park, VT: Antimicrobial Therapy, Inc; 2006. 8. Shah PB, Giudice JC, Griesback R, et al. Review article: The newer guidelines for the management of community-acquired pneumonia. JAOA 2004;104(12):521-526. 9. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72.

Page 387 Ketoprofen and Ketoprofen ER - Step Therapy

Prior Authorization Guideline

GL-89788 Ketoprofen and Ketoprofen ER - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 5/15/2020 P&T Revision Date: 6/16/2021

1 . Indications Drug Name: Ketoprofen Rheumatoid Arthritis and Osteoarthritis: Indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis

Pain: Indicated for the management of pain

Primary Dysmenorrhea: Indicated for the treatment of primary dysmenorrhea

Drug Name: Ketoprofen Extended-Release (ER) Rheumatoid Arthritis and Osteoarthritis: Indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis

2 . Criteria

Page 388

Product Name: Ketoprofen, Ketoprofen ER [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of failure, contraindication, or intolerance to three of the following oral products:

• diclofenac • flurbiprofen • ibuprofen (prescription strength) • naproxen (prescription strength)

3 . Background

Benefit/Coverage/Program Information

Background: Ketoprofen is a non-steroidal anti-inflammatory (NSAID) for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis, for the management of pain, and for treatment of primary dysmenorrhea. Ketoprofen extended-release is indicated for indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Extended-release ketoprofen is not indicated for acute pain.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. Additional Clinical Programs:

Page 389 program and/or therapeutic class. • Supply limits may also be in place.

4 . References

1. Ketoprofen [package insert]. East Brunswick, NJ: Avet Pharmaceuticals Inc.; March 2021. 2. Ketoprofen extended-release [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; March 2021.

5 . Revision History

Date Notes

7/12/2021 No updates to criteria. Updated references.

Page 390 Klisyri (tirbanibulin) - Step Therapy

Prior Authorization Guideline

GL-89376 Klisyri (tirbanibulin) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 6/16/2021

P&T Revision Date:

1 . Indications Drug Name: Klisyri (tirbanibulin) Actinic Keratosis Indicated for the topical treatment of actinic keratosis of the face or scalp.

2 . Criteria

Product Name: Klisyri [a] Approval Length 1 month(s) Guideline Type Step Therapy

Approval Criteria

Page 391

1 - History of failure, contraindication, or intolerance to two of the following:

• diclofenac 3% gel (generic Solaraze) • topical fluorouracil (e.g., Carac, generic Efudex) • imiquimod (e.g., generic Aldara)

3 . Background

Benefit/Coverage/Program Information

Background: Klisyri is a microtubule inhibitor indicated for the topical treatment of actinic keratosis of the face or scalp.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. Additional Clinical Programs:

4 . References

1. Klisyri [package insert]. Exton, PA: Almirall, LLC; December 2020. 2. Carac [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; May 2017. 3. Efudex [package insert]. Bridgewater, NJ: Bausch Health US, LLC; April 2020. 4. Aldara [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; April 2018. 5. McIntyre, WJ et al. Treatment Options for Actinic Keratoses. Am Fam Physicians. 2007. Sept 1;76(5):667-571.

Page 392

5 . Revision History

Date Notes

7/2/2021 New program.

Page 393 Lampit (nifurtimox)

Prior Authorization Guideline

GL-78629 Lampit (nifurtimox)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 11/13/2020

P&T Revision Date:

1 . Indications Drug Name: Lampit (nifurtimox) Chagas Disease Indicated in pediatric patients (birth to less than 18 years of age and weighing at least 2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi.

2 . Criteria

Product Name: Lampit Approval Length 60 Day(s) Guideline Type Notification

Page 394

Approval Criteria

1 - Diagnosis of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi

3 . Background

Benefit/Coverage/Program Information

Background:

Lampit is a nitrofuran antiprotozoal indicated in pediatric patients (birth to less than 18 years of age and weighing at least 2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi.

Additional Clinical Rules:

4 . References

1. Lampit [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; Aug 2020. 2. CDC Guidelines. Parasites – American Trypanosomiasis (also known as Chagas Disease). https://www.cdc.gov/parasites/chagas/. Accessed October 2020.

Page 395 5 . Revision History

Date Notes

12/18/2020 New program.

Page 396 Levemir (insulin detemir)

Prior Authorization Guideline

GL-71229 Levemir (insulin detemir)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/17/2019 P&T Revision Date: 7/15/2020

1 . Criteria

Product Name: Levemir (insulin detemir)* [a] Approval Length 9 month(s) Guideline Type Non Formulary

Approval Criteria

1 - Patient is pregnant

AND

Page 397

2 - History of failure, contraindication, or intolerance to insulin NPH Notes * Levemir is typically excluded from coverage. [a] State mandates may apply. Any federal regulatory requirements and the member specific be nefit plan coverage may also impact coverage criteria. Other policies a nd utilization management programs may apply.

2 . Background

Benefit/Coverage/Program Information

Background:

The Endocrine Society recommends insulin NPH, an intermediate acting insulin, as the preferred basal insulin in pregnancy. Patients may be switched to Levemir, a long-acting insulin, when therapy with insulin NPH is inadequate. This program allows for coverage of Levemir for pregnant patients when they have failed therapy with insulin NPH.

Additional Clinical Rules:

3 . References

1. American Diabetes Association: Standards of Medical Care in Diabetes. Clinical Diabetes. 2020 Jan 38(1): 10-38. 2. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk; March 2020. 3. Ian Blumer, Eran Hadar, David R. Hadden, Lois Jovanovič, Jorge H. Mestman, M. Hassan Murad, Yariv Yogev, Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 11, 1 November 2013, Pages 4227–4249. 4. American Diabetes Association; Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes- 2020. Diabetes Care 2020;43 (Suppl. 1):S183-S192.

4 . Revision History

Page 398 Date Notes

8/7/2020 Annual review. Updated references.

Page 399 Lidoderm (Lidocaine Patch 5%) and ZTLido (lidocaine topical system)

Prior Authorization Guideline

GL-68098 Lidoderm (Lidocaine Patch 5%) and ZTLido (lidocaine topical system)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2020 P&T Approval Date: 4/15/2020

P&T Revision Date:

1 . Indications Drug Name: Lidoderm (Lidocaine Patch 5%), ZTLido (lidocaine topical system) Pain associated with post-herpetic neuralgia Indicated for the relief of pain associated with post-herpetic neuralgia (PHN).

2 . Criteria

Product Name: Lidocaine Patch (generic Lidoderm) Diagnosis Pain associated with post-herpetic neuralgia Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 400

Approval Criteria

1 - One of the following:

1.1 Diagnosis of post-herpetic neuralgia

1.2 Diagnosis of neuropathic pain

AND

2 - Patch will be applied only to intact skin

Product Name: Brand Lidoderm, ZTLido Diagnosis Pain associated with post-herpetic neuralgia Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization or Nonformulary

Approval Criteria

1 - One of the following:

1.1 Diagnosis of post-herpetic neuralgia

1.2 Diagnosis of neuropathic pain

AND

2 - Patch will be applied only to intact skin

Page 401

AND

3 - History of failure, contraindication, or intolerance to the following: lidocaine patch (generic Lidoderm)

Product Name: Lidocaine patch (generic Lidoderm), Brand Lidoderm, ZTLido Diagnosis Pain associated with post-herpetic neuralgia Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization or Nonformulary

Approval Criteria

1 - Documentation of positive clinical response to therapy

3 . Background

Benefit/Coverage/Program Information

Background

Lidocaine patch (Lidoderm) and ZTLido are indicated for the relief of pain associated with post- herpetic neuralgia (PHN). The American Academy of Neurology recommends the use of lidocaine patch as an option for the management of PHN. Evidence also exists in support of using lidocaine patch for non-PHN neuropathies.

Additional Clinical Rules

• Supply limits may be in place.

Page 402 4 . References

1. Baron, R., Allegri, M., Correa-Illanes, G., et al. The 5% Lidocaine-Medicated Plaster: Its Inclusion in International Treatment Guidelines for Treating Localized Neuropathic Pain, and Clinical Evidence Supporting its Use. Pain Ther. 2016;5:149. 2. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of Painful Diabetic Neuropathy. Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011 May 17;76(20):1758-65. 3. Derry S, Wiffen PJ, Moore RA, et al. Topical Lidocaine for Neuropathic Pain in Adults (Review). Cochrane Database of Systemic Reviews 2014;7:1-41. 4. Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice Parameter: Treatment of Postherpetic Neuralgia. An Evidence-Based Report on the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004 Sep 28;63(6):959-65. 5. Dworkin, R., Johnson, R., Breuer, J., et al. Recommendations for the Management of Herpes Zoster. Clinical Infectious Diseases. 2007;44:S1-S26. 6. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for Neuropathic Pain in Adults: Systematic Review, Meta-analysis and Updated NeuPSIG Recommendations. The Lancet Neurology. 2015;14(2):162-173. 7. Gilron, Ian et al. Neuropathic Pain: Principles of Diagnosis and Treatment. Mayo Clinic Proceedings, Volume 90, Issue 4, 532-545. 8. Hooten M, Thorson D, Bianco J, et al. Institute for Clinical Systems Improvement. Pain: Assessment, Non-Opioid Treatment Approaches and Opioid Management. Updated August 2017. https://www.icsi.org/_asset/f8rj09/Pain.pdf. Accessed February 28, 2020. 9. Lidoderm Prescribing Information. Endo Pharmaceuticals. Malvern, PA. November 2018. 10. ZTLido Prescribing Information. Scilex Pharmaceuticals Inc. San Diego, CA. November 2018.

5 . Revision History

Date Notes

7/1/2020 4/2020 P&T - New program.

Page 403 Lidoderm (Lidocaine Patch), ZTLido

Prior Authorization Guideline

GL-90386 Lidoderm (Lidocaine Patch), ZTLido

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 2/17/2017 P&T Revision Date: 04/15/2020 ; 6/16/2021

1 . Indications Drug Name: Lidoderm (Lidocaine Patch), ZTLido Pain associated with post-herpetic neuralgia (PHN) Indicated for the relief of pain associated with post-herpetic neuralgia (PHN). The American Academy of Neurology recommends the use of lidocaine patch as an option for the management of PHN. Evidence also exists in support of using lidocaine patch for non-PHN neuropathies.

2 . Criteria

Product Name: Brand Lidoderm patch, Generic lidocaine patch, Brand ZTLido patch* Approval Length 6 month(s) Therapy Stage Initial Authorization

Page 404 Guideline Type Notification

Approval Criteria

1 - One of the following:

• Diagnosis of post-herpetic neuralgia • Diagnosis of neuropathic pain

AND

2 - Patch will be applied only to intact skin Notes *Applies to brand and generic lidocaine patches. Brand Lidoderm and ZTLido are typically excluded from coverage.

Product Name: Brand Lidoderm patch, Generic lidocaine patch, Brand ZTLido patch* Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to therapy Notes *Applies to brand and generic lidocaine patches. Brand Lidoderm and ZTLido are typically excluded from coverage.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Page 405 Background: Lidocaine patch (Lidoderm) and ZTLido are indicated for the relief of pain associated with post- herpetic neuralgia (PHN). The American Academy of Neurology recommends the use of lidocaine patch as an option for the management of PHN. Evidence also exists in support of using lidocaine patch for non-PHN neuropathies.

4 . References

1. Baron, R., Allegri, M., Correa-Illanes, G., et al. The 5% Lidocaine-Medicated Plaster: Its Inclusion in International Treatment Guidelines for Treating Localized 2. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of Painful Diabetic Neuropathy. Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011 May 17; 76(20):1758-65. 3. Derry S, Wiffen PJ, Moore RA, et al. Topical Lidocaine for Neuropathic Pain in Adults (Review). Cochrane Database of Systemic Reviews 2014; 7: 1-41. 4. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for Neuropathic Pain in Adults: Systematic Review, Meta-analysis and Updated NeuPSIG Recommendations. The Lancet Neurology. 2015; 14(2):162-173. 5. Gilron, Ian et al. Neuropathic Pain: Principles of Diagnosis and Treatment. Mayo Clinic Proceedings, Volume 90, Issue 4, 532 – 545. 6. Hooten M, Thorson D, Bianco J, et al. Institute for Clinical Systems Improvement. Pain: Assessment, Non-Opioid Treatment Approaches and Opioid Management. Updated August 2017. https://www.icsi.org/_asset/f8rj09/Pain.pdf. Accessed May 5, 2021. 7. Lidoderm [package insert]. Malvern, PA: Endo Pharmaceuticals; November 2018. 8. ZTLido [package insert]. San Diego, CA: Scilex Pharmaceuticals Inc; April 2021.

5 . Revision History

Date Notes

7/26/2021 Annual review. Updated references.

Page 406 Linzess (linaclotide), Symproic (naldemedine)

Prior Authorization Guideline

GL-81552 Linzess (linaclotide), Symproic (naldemedine)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 3/1/2021 P&T Approval Date: 9/19/2018 P&T Revision Date: 06/19/2019 ; 12/16/2020

1 . Indications Drug Name: Linzess (linaclotide) Chronic idiopathic constipation Indicated for the treatment of chronic idiopathic constipation in adults aged 18 years and older.

Irritable bowel syndrome Indicated for the treatment of irritable bowel syndrome with constipation in adults aged 18 years and older.

Drug Name: Symproic (naldemedine) Opioid-induced constipation Indicated for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g.weekly) opioid dosage escalation

2 . Criteria

Page 407

Product Name: Linzess Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

• Chronic idiopathic constipation • Irritable bowel syndrome with constipation

AND

2 - Patient is greater than or equal to 18 years of age

Product Name: Symproic Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

• Diagnosis of opioid-induced constipation in patients being treated for chronic, non- cancer pain • Diagnosis of opioid-induced constipation in patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation

Product Name: Linzess or Symproic Approval Length 12 month(s) Therapy Stage Reauthorization

Page 408 Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to therapy

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Programs:

Background

Linzess (linaclotide) is indicated for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation in adults aged 18 years and older. Symproic (naldemedine) is an opioid antagonist indicated for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g.weekly) opioid dosage escalation. Physicians and patients should periodically assess the need for continued treatment with these agents.

4 . References

1. Linzess [package insert]. Madison, NJ: Allergan USA Inc.; September 2020. 2. Symproic [package insert]. Shionogi Inc. Florham Park, NJ: Shionogi Inc.; May 2020.

5 . Revision History

Date Notes

2/25/2021 12/2020 P&T - Annual review. Updated references.

Page 409 Lithobid (lithium carbonate) - PA/Med Nec

Prior Authorization Guideline

GL-84791 Lithobid (lithium carbonate) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 3/17/2021

P&T Revision Date:

1 . Criteria

Product Name: Lithobid (brand only) [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Both of the following:

1.1 History of greater than or equal to 4 week trial of generic lithium (document date of trial)

Page 410

AND

1.2 One of the following:

• History of an inadequate response to generic lithium despite therapeutic levels (0.6 to 1.2 mEq/L) • History of the inability to achieve or maintain therapeutic levels despite adequate dosing adjustments

2 - History of an intolerance to generic lithium which was unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. change timing of dosing, divide daily dose out for more frequent but smaller doses, lowering dose)

3 - Currently established on Lithobid and stable for at least 6 months. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Lithobid (brand only) [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Page 411

2 . Background

Benefit/Coverage/Program Information

Background: This program requires a member to try an AB-rated generic lithium prior to receiving coverage for brand Lithobid. Additional Clinical Rules:

3 . References

1. Lithobid [package insert]. Baudette, MN: ANI Pharmaceuticals, Inc; February 2020. 2. Gitlin, M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016;4(1):27. Epub 2016 Dec 17.

4 . Revision History

Date Notes

4/30/2021 New program.

Page 412 Lokelma (sodium zirconium cyclosilicate), Veltassa (patiromer) - PA/Med Nec

Prior Authorization Guideline

GL-89786 Lokelma (sodium zirconium cyclosilicate), Veltassa (patiromer) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 6/22/2016 P&T Revision Date: 03/18/2020 ; 6/16/2021

1 . Indications Drug Name: Lokelma (sodium zirconium cyclosilicate), Veltassa (patiromer) Hyperkalemia Indicated for the treatment of hyperkalemia.

2 . Criteria

Product Name: [Lokelma, Veltassa] [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 413

Approval Criteria

1 - Diagnosis of non-life threatening hyperkalemia

AND

2 - Where clinically appropriate, medications known to cause hyperkalemia (e.g. angiotensin- converting enzyme inhibitor, angiotensin II receptor blocker, aldosterone antagonist, NSAIDs) have been discontinued or reduced to the lowest effective dose

AND

3 - Where clinically appropriate, loop or thiazide diuretic therapy for potassium removal has failed

AND

4 - Patient follows a low potassium diet (less than or equal to 3 grams per day) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y

Product Name: [Lokelma, Veltassa] [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient has a positive clinical response to Lokelma or Veltassa therapy and continues to require treatment for hyperkalemia

AND

Page 414

AND

3 - Patient follows a low potassium diet (less than or equal to 3 grams per day) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Lokelma and Veltassa are indicated for the treatment of hyperkalemia. Lokelma and Veltassa should not be used as an emergency treatment for life threatening hyperkalemia because of its delayed onset of action. Non-emergent hyperkalemia is generally treated by addressing the reversible causes, such as removing drugs that may be causing impaired renal function, removing or adjusting medications that directly cause hyperkalemia, and initiating therapies for potassium removal.

4 . References

1. Veltassa [package insert]. Redwood City, CA; Relypsa, Inc.: May 2018. 2. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med 2015; 372:211. 3. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin- aldosterone system. N Engl J Med 2004; 351:585. 4. Khanna A, White WB. The management of hyperkalemia in patients with cardiovascular disease. Am J Med. 2009 Mar. 122(3):215-21

Page 415 5. Lokelma [package insert]. Wilmington, DE; AstraZeneca: October 2020. 6. Mount D. Treatment and prevention of hyperkalemia in adults. Sterns, R (Ed). UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on May 6, 2021.)

5 . Revision History

Date Notes

7/12/2021 Updated references.

Page 416 Long-Acting Opioids

Prior Authorization Guideline

GL-90140 Long-Acting Opioids

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 3/22/2017 P&T Revision Date: 04/15/2020 ; 5/21/2021

1 . Indications Drug Name: morphine sulfate controlled-release caps, Duragesic (including fentanyl transdermal), hydromorphone ER, Hysingla ER, morphine sulfate sustained-release caps, MS Contin, Nucynta ER, oxycodone hcl ER, OxyContin, oxymorphone ER, Xtampza ER, Zohydro ER Management of moderate to severe pain Indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid is needed for an extended period of time and for which alternative treatment options are not appropriate. They are not intended for use as an as needed analgesic.

2 . Criteria

Product Name: [fentanyl transdermal patch (generic Duragesic) 12, 25, 50, 75, 100 mcg/hr, methadone, morphine sulfate controlled-release tablets (generic MS Contin), Nucynta ER,

Page 417 Xtampza ER] [a] Diagnosis Book of Business: Cancer or End of Life (defined as a <2 year life expectancy) related pain Approval Length 24 months up to the dose allowed by supply limit review Guideline Type Prior Authorization or Non Formulary

Approval Criteria

1 - Patient requires treatment with opioids due to active cancer diagnosis or end of life related pain (document cancer diagnosis or for end of life, expectancy of < 2 years) Notes [a] State mandates may apply. Any federal regulatory requirements an d the patient specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply . Authorization will be issued for 24 months up to the dose allowed by s upply limit review (please refer to supply limit criteria). If the patient is c urrently taking the requested long-acting opioid OR was recently switch ed from another long-acting opioid and does not meet the medical nec essity initial authorization criteria requirements for long-acting opioids, a denial should be issued and a maximum 90-day authorization may b e authorized one time for the requested drug/strength combination up t o the requested quantity for transition to an alternative treatment.

Product Name: [morphine sulfate controlled-release capsules (generic Avinza), Duragesic^, fentanyl transdermal patch (37.5, 62.5, 87.5 mcg/hr)^, Hysingla ER^, morphine sulfate sustained-release capsules (generic Kadian), MS Contin, Oxycontin^, oxycodone controlled- release (authorized generic for OxyContin)^, oxymorphone extended release, and Zohydro ER^ [Applies to all brand and generic versions of listed products except generic morphine sulfate controlled-release tablets (generic MS Contin) and fentanyl transdermal patch (generic Duragesic strengths)]] [a] Diagnosis Book of Business: Cancer or End of Life (defined as a <2 year life expectancy) Approval Length 24 months up to the dose allowed by supply limit review Guideline Type Prior Authorization or Non Formulary

Approval Criteria

1 - Patient requires treatment with opioids due to active cancer diagnosis or end of life related pain (document cancer diagnosis or for end of life, expectancy of < 2 years)

Page 418 AND

2 - One of the following:

2.1 History of failure, contraindication or intolerance to a trial of ALL of the following (Document date of trial):

• Nucynta ER • morphine sulfate controlled release tablets (generic MS Contin) • Xtampza ER • For Brand Duragesic requests: fentanyl transdermal patch (generic Duragesic)

2.2 Patient is established on pain therapy with the requested medication for cancer-related or end of life pain (< 2 years life expectancy), and the medication is not a new regimen for the treatment of cancer-related or end of life (< 2 years life expectancy) pain.

2.3 Request is for OxyContin or oxycodone controlled-release (Authorized Generic for OxyContin) and one of the following:

2.3.1 Both of the following:

2.3.1.1 The patient requires more than or equal to 320 mg/day of controlled-release oxycodone.

AND

2.3.1.2 The patient has a history of failure, contraindication or intolerance to BOTH of the following (Document date of trial):

• Nucynta ER • morphine sulfate controlled-release tablets (specifically generic MS Contin)

2.3.2 Both of the following:

Page 419 2.3.2.1 The patient requires less than 320 mg/day of controlled-release oxycodone.

AND

2.3.2.2 The patient has a history of failure, contraindication or intolerance to ALL of the following (Document date of trial):

• Nucynta ER • morphine sulfate controlled-release tablets (generic MS Contin) • Xtampza ER

Notes [a] State mandates may apply. Any federal regulatory requirements an d the patient specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply . Authorization will be issued for 24 months up to the dose allowed by s upply limit review (please refer to supply limit criteria). If the patient is c urrently taking the requested long-acting opioid OR was recently switch ed from another long-acting opioid and does not meet the medical nec essity initial authorization criteria requirements for long-acting opioids, a denial should be issued and a maximum 90-day authorization may b e authorized one time for the requested drug/strength combination up t o the requested quantity for transition to an alternative treatment.

Product Name: [fentanyl transdermal patch (generic Duragesic) 12, 25, 50, 75, 100 mcg/hr, methadone, morphine sulfate controlled-release tablets (generic MS Contin), Nucynta ER, Xtampza ER] [a] Diagnosis Book of Business: Non-cancer and Non-End of Life pain Approval Length 6 months up to the dose allowed by supply limit review Therapy Stage Initial Authorization Guideline Type Prior Authorization or Non Formulary

Approval Criteria

1 - Prescriber attests to ALL of the following:

• The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided. • Patient has been screened for substance abuse/opioid dependence. • Pain is moderate to severe and expected to persist for an extended period of time (chronic).

Page 420

AND

2 - Treatment goals are defined and include estimated duration of treatment (must document treatment goals)

AND

3 - Patient has been screened for underlying depression and/or anxiety. If applicable, any underlying conditions have been or will be addressed.

AND

4 - One of the following:

4.1 The patient is new to the plan (as evidenced by coverage effective date of less than or equal to 120 days) and is currently established on the requested long-acting opioid.

4.2 One of the following

4.2.1 All of the following:

4.2.1.1 The patient is being treated for moderate to severe chronic pain that is non- neuropathic (examples of neuropathic pain include neuralgias, neuropathies, fibromyalgia)

AND

4.2.1.2 Prior to the start of therapy with the long-acting opioid, the patient has failed an adequate (minimum of 4 week) trial of a short-acting opioid. (Document drug(s) and date of trial).

4.2.2 All of the following:

4.2.2.1 The patient is being treated for moderate to severe neuropathic pain or fibromyalgia

Page 421

AND

4.2.2.2 Unless it is contraindicated, the patient has not exhibited an adequate response to 8 weeks of treatment with gabapentin titrated to a therapeutic dose. (Document date of trial)

AND

4.2.2.3 Unless it is contraindicated, the patient has not exhibited an adequate response to at least 6 weeks of treatment with a tricyclic antidepressant titrated to the maximum tolerated dose. (Document drug and date of trial) Notes [a] State mandates may apply. Any federal regulatory requirements an d the patient specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply . Authorization will be issued for 6 months for non-cancer and non-end of life pain up to the dose allowed by supply limit review (please refer t o supply limit criteria). If the patient is currently taking the requested lon g-acting opioid OR was recently switched from another long-acting opi oid and does not meet the medical necessity initial authorization criteri a requirements for long-acting opioids, a denial should be issued and a maximum 90-day authorization may be authorized one time for the req uested drug/strength combination up to the requested quantity for trans ition to an alternative treatment.

Product Name: [Duragesic, fentanyl transdermal (37.5, 62.5, 87.5 mcg/hr), hydromorphone extended-release (generic Exalgo), Hysingla ER, morphine sulfate controlled-release capsules (generic Avinza), morphine sulfate sustained-release capsules (generic Kadian), MS Contin, OxyContin, oxycodone controlled-release (Authorized Generic of OxyContin), oxymorphone extended release, and Zohydro ER [Applies to all brand and generic versions of listed products except generic morphine sulfate controlled-release tablets (generic MS Contin) and fentanyl transdermal patch (generic Duragesic strengths)]] [a] Diagnosis Book of Business: Non-cancer and Non-End of Life pain Approval Length 6 months up to the dose allowed by supply limit review Therapy Stage Initial Authorization Guideline Type Prior Authorization or Non Formulary

Approval Criteria

1 - Prescriber attests to ALL of the following:

Page 422 • The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided. • Patient has been screened for substance abuse/opioid dependence. • Pain is moderate to severe and expected to persist for an extended period of time (chronic).

AND

2 - Treatment goals are defined and include estimated duration of treatment (must document treatment goals)

AND

3 - Patient has been screened for underlying depression and/or anxiety. If applicable, any underlying conditions have been or will be addressed

AND

4 - One of the following:

4.1 Both of the following:

4.1.1 The patient is being treated for moderate to severe chronic pain that is non-neuropathic (examples of neuropathic pain include neuralgias, neuropathies, fibromyalgia)

AND

4.1.2 Prior to the start of therapy with the long-acting opioid, the patient has failed an adequate (minimum of 4 week) trial of a short-acting opioid (Document drug(s) and date of trial)

4.2 All of the following:

4.2.1 The patient is being treated for moderate to severe neuropathic pain or fibromyalgia

Page 423 AND

4.2.2 Unless it is contraindicated, the patient has not exhibited an adequate response to 8 weeks of treatment with gabapentin titrated to a therapeutic dose (Document date of trial)

AND

4.2.3 Unless it is contraindicated, the patient has not exhibited an adequate response to at least 6 weeks of treatment with a tricyclic antidepressant titrated to the maximum tolerated dose (Document drug and date of trial)

AND

4.2.4 The patient has a history of failure, contraindication or intolerance to a trial of all of the following (Document date of trials):

• Nucynta ER • morphine sulfate controlled-release tablets (generic MS Contin) • Xtampza ER • For Brand Duragesic requests: fentanyl transdermal patch (generic Duragesic)

Notes [a] State mandates may apply. Any federal regulatory requirements an d the patient specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply . Authorization will be issued for 6 months for non-cancer and non-end of life pain up to the dose allowed by supply limit review (please refer t o supply limit criteria). If the patient is currently taking the requested lon g-acting opioid OR was recently switched from another long-acting opi oid and does not meet the medical necessity initial authorization criteri a requirements for long-acting opioids, a denial should be issued and a maximum 90-day authorization may be authorized one time for the req uested drug/strength combination up to the requested quantity for trans ition to an alternative treatment.

Page 424 Approval Length 6 months up to the dose allowed by supply limit review Therapy Stage Reauthorization Guideline Type Prior Authorization or Non Formulary

Approval Criteria

1 - Documented meaningful improvement in pain and function when assessed against treatment goals (Document improvement in function or pain score improvement)

AND

2 - Document rationale for not tapering or discontinuing opioid if treatment goals are not being met

AND

3 - Prescriber attests to ALL of the following:

• Patient has been screened for substance abuse/opioid dependence. • The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided. • Pain is moderate to severe and expected to persist for an extended period of time (chronic).

Notes [a] State mandates may apply. Any federal regulatory requirements an d the patient specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply . Authorization will be issued for 6 months for non-cancer and non-end of life pain up to the dose allowed by supply limit review (please refer t o supply limit criteria). If the patient is currently taking the requested lon g-acting opioid OR was recently switched from another long-acting opi oid and does not meet the medical necessity reauthorization criteria re quirements for long-acting opioids, a denial should be issued and a ma ximum 90-day authorization may be authorized one time for the reques ted drug/strength combination up to the requested quantity for transitio n to an alternative treatment.

3 . Background

Page 425 Clinical Practice Guidelines

CDC and the American Academy of Neurology:

The CDC and the American Academy of Neurology recommends the following best practices in the prescription of long-acting opioids:

• Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. • Before starting opioid therapy, treatment goals should be established with patients that include realistic goals for pain and function and should consider how therapy will be discontinued if benefits do not outweigh risks.Track pain and function at every visit (at least every 3 months) using a brief, validated instrument.Continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. • When starting opioid therapy for chronic pain, clinicians should prescribe immediate- release opioids instead of extended release/long-acting opioids. • Document the daily morphine milligram equivalent (MME) in mg/day from all sources of opioids.Access the state prescription drug monitoring program (PDMP) data at treatment initiation and periodically during treatment.Currently all states except for Missouri have a PDMP. • To avoid increased risk of respiratory depression, long-acting opioids should not be prescribed concurrently with benzodiazepines.Screen for past and current substance abuse and for severe depression, anxiety, and PTSD prior to initiation. • Use random urine drug screening prior to initiation and periodically during treatment with a frequency according to risk. • Use a patient treatment agreement, signed by both the patient and prescriber that addresses risks of use and responsibilities of the patient.Avoid escalating doses above 50-90 mg/day MME unless sustained meaningful improvement in pain and function is attained, and not without consultation with a pain management specialist. • Clinicians should evaluate benefits and harms of continued therapy at least every 3 months.If benefits do not outweigh harms, opioids should be tapered and discontinued.Evaluation should include assessment of substance use disorder/opioid dependence.Validated scales (such as the DAST-10) are available at www.drugabuse.gov.

Benefit/Coverage/Program Information Background:

Long-acting opioid analgesics, morphine sulfate controlled-release capsules, Duragesic (including fentanyl transdermal), hydromorphone ER, Hysingla ER, morphine sulfate sustained- release capsules, MS Contin, Nucynta ER, oxycodone hcl ER, OxyContin, oxymorphone ER, Xtampza ER and Zohydro ER are indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid is needed for an extended period of time and for which alternative treatment options are not appropriate. They are not intended for use as an as needed analgesic.

Long-acting opioids are not indicated for pain in the immediate postoperative period (the first

Page 426 12-24 hours following surgery), or if the pain is mild, or not expected to persist for an extended period of time. They are only indicated for postoperative use if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate.

Long-acting opioids should not be used in treatment naïve patients. Physicians should individualize treatment in every case, initiating therapy at the appropriate point along a progression from non-opioid analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen to opioids in a plan of pain management such as those outlined by the World Health Organization, the Agency for Healthcare Research and Quality, the Federation of State Medical Boards Model Guidelines, or the American Pain Society.

Additional Clinical Rules:

• Supply limits may be in place. • MMELIMIT (Cumulative Opioid Review) is in place and can be utilized for individual supply limit reviews

^ Duragesic, Hysingla ER, fentanyl 37.5, 62.5 and 87.5 mcg/hr, Kadian (brand and generic), oxycodone controlled-release (authorized generic for OxyContin), and OxyContin are typically excluded from coverage. Please refer to plan specifics to determine exclusion status.

4 . References

1. Hydromorphone extended-release [package insert]. Webster Grover, MO: Mallinckrodt, Inc.; January 2021. 2. Hysingla ER [package insert]. Stanford, CT: Purdue Pharma; March 2021. 3. MS Contin [package insert]. Stanford, CT. Purdue Pharma; March 2021. 4. Nucynta ER [package insert]. Stoughton, MA: Collegium Pharmaceuticals, Inc. March 2021. 5. Oxymorphone Extended Release [package insert]. Brookhaven, NY. Amneal Pharmaceuticals of NY, LLC.; April 2021. 6. OxyContin [package insert]. Stanford, CT: urdue Pharma; March 2021. 7. Zohydro ER [package insert]. Princeton, NJ: Pernix Therapeutics; March 2021. 8. Duragesic [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. March 2021. 9. Xtampza ER [package insert]. Stoughton, MA: Collegium Pharmaceuticals, Inc. March 2021. 10. Palermo T, et al. Assessment and management of children with chronic pain. A position statement from the American Pain Society. 2012. Available at: http://americanpainsociety.org/uploads/get-involved/pediatric-chronic-pain-statement.pdf 11. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. JAMA. Published online March 15, 2016. 12. Spatar, SB. Standardizing the use of mental health screening instruments in patients with pain. Fed Pract. 2019 Oct; 36 (Suppl 6): S28-S30

Page 427 13. Sullivan MD. Depression effects on long-term prescription opioid use, abuse, and addiction. Clin J Pain. 2018 Sep;34(9):878-884.

5 . Revision History

Date Notes

7/20/2021 5/2021 P&T - Removed products no longer on the market. Revised pro vider attestation. Added requirements for documentation of treatment g oals and screening for underlying depression and anxiety. Administrati ve changes and references updated.

Page 428 Lonhala Magnair (glycopyrrolate inhalation solution), Yupelri (revefenacin inhalation solution) - PA/Med Nec

Prior Authorization Guideline

GL-74547 Lonhala Magnair (glycopyrrolate inhalation solution), Yupelri (revefenacin inhalation solution) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 9/18/2018 P&T Revision Date: 08/14/2020 ; 11/13/2020

1 . Indications Drug Name: Lonhala Magnair, Yupelri Chronic obstructive pulmonary disease (COPD) Indicated for the long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

2 . Criteria

Product Name: Lonhala Magnair * [a] Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 429 Guideline Type Prior Authorization

Approval Criteria

1 - All of the following:

1.1 Diagnosis of moderate to severe chronic obstructive pulmonary disease (COPD)

AND

1.2 One of the following:

1.2.1 History of failure, contraindication or intolerance to all of the following:

• Incruse Ellipta (umeclidinium) • Spiriva Handihaler or Respimat (tiotropium) • Yupelri (revefenacin inhalation solution)

1.2.2 Both of the following:

1.2.2.1 Patient is unable to use a metered-dose, dry powder or slow mist inhaler (e.g. Incruse Ellipta, Spiriva Respimat) to control his/her COPD due to one of the following:

1.2.2.1.1 Cognitive or physical impairment limiting coordination of handheld devices (e.g., cognitive decline, arthritis in the hands) (Document impairment)

1.2.2.1.2 Patient is unable to generate adequate inspiratory force (e.g., peak inspiratory flow rate (PIFR) resistance is less than 60 L/min)

AND

1.2.2.2 History of failure, contraindication or intolerance to Yupelri (revefenacin inhalation solution) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage

Page 430 criteria. Other policies and utilization management programs may appl y. *Lonhala Magnair is typically excluded from coverage

Product Name: Yupelri [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe chronic obstructive pulmonary disease (COPD)

AND

2 - One of the following:

2.1 History of failure, contraindication or intolerance to both of the following:

• Incruse Ellipta (umeclidinium) • Spiriva Handihaler or Respimat (tiotropium)

2.2 Patient is unable to use a metered-dose, dry powder or slow mist inhaler (e.g. Incruse Ellipta, Spiriva Respimat) to control his/her COPD due to one of the following:

• Cognitive or physical impairment limiting coordination of handheld devices (e.g., cognitive decline, arthritis in the hands) (Document impairment) • Patient is unable to generate adequate inspiratory force (e.g., peak inspiratory flow rate (PIFR) resistance is less than 60 L/min)

Product Name: Lonhala Magnair*, Yupelri [a] Approval Length 12 month(s)

Page 431 Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules: 1. Additional Clinical Rules: 2. Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. 3. Supply limits may be in place. Background: Lonhala Magnair (glycopyrrolate inhalation solution)* and Yupelri (revefenacin inhalation solution) are nebulized long-acting antimuscarinic (anticholinergic) agents indicated for the long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

4 . References

1. Global strategy for the diagnosis, management and prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2020. 2. Lonhala Magnair [package insert]. Marlborough, MA: Sunovian Pharmaceuticals Inc. June 2019. 3. Yupelri [package insert]. Morgantown, WV: Mylan Specialty L.P. May 2019. 4. Ferguson GT, Goodin T, Tosiello R, et al. Long-term safety of glycopyrrolate/eFlow CS in moderate-to-very severe COPD: results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 5 randomized study. Respiratory Medicine 132; 2017:251-60.

Page 432 5. Wise RA, Acevedo RA, Anzueto AR, et al. Guiding principles for the use of nebulized long-acting beta2-agonists in patients with COPD: An expert panel consensus. Chronic Obstr Pulm Dis 2017; 4(1): 7-20

5 . Revision History

Date Notes

12/21/2020 Updated criteria/formatting for Lonhala Magnair to clarify that patient m ust meet diagnosis requirement, as well as have a hx of failure, contrai ndication or intolerance to the metered dose inhalers. Posting as a sup plemental ahead of Nov P&T.

Page 433 Lotronex (alosteron) - Notification

Prior Authorization Guideline

GL-77833 Lotronex (alosteron) - Notification

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 5/21/2013 P&T Revision Date: 10/16/2019 ; 11/13/2020

1 . Indications Drug Name: Lotronex (alosetron) Severe diarrhea-predominant irritable bowel syndrome (IBS) Indicated only for use in women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have chronic IBS, anatomical or biochemical abnormalities of the gastrointestinal tract have been excluded and have not responded to conventional therapy.

2 . Criteria

Product Name: Lotronex* Approval Length 6 month(s) Therapy Stage Initial Authorization

Page 434 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of severe diarrhea-predominant irritable bowel syndrome (IBS) with symptoms for at least six months

AND

2 - Patient was female at birth

AND

3 - Has not responded adequately to conventional therapy (e.g., loperamide, antispasmodics) Notes *Brand Lotronex is typically excluded from coverage. Tried/failed criteri a may be in place. Please refer to plan specifics to determine coverage status.

Product Name: Lotronex* Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Lotronex will be approved based on documentation of positive clinical response to Lotronex therapy Notes *Brand Lotronex is typically excluded from coverage. Tried/failed criteri a may be in place. Please refer to plan specifics to determine coverage status.

3 . Background

Benefit/Coverage/Program Information

Page 435 Additional Clinical Programs:

Lotronex (alosteron) is indicated only for use in women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have chronic IBS, anatomical or biochemical abnormalities of the gastrointestinal tract have been excluded and have not responded to conventional therapy.

4 . References

1. Lotronex [package insert] San Diego, CA: Promethus Therapeutics and Diagnostics; January 2016.

5 . Revision History

Date Notes

12/4/2020 Annual review. Updated references.

Page 436 Lucemyra (lofexidine) - PA/Med Nec

Prior Authorization Guideline

GL-81161 Lucemyra (lofexidine) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 11/16/2018 P&T Revision Date: 11/15/2019 ; 1/20/2021

1 . Indications Drug Name: Lucemyra (lofexidine) Opioid withdrawal symptoms Indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.

2 . Criteria

Product Name: Lucemyra [a] Approval Length 14 days; If Lucemyra was initiated in the inpatient setting, the total course of therapy should not exceed 14 days. Guideline Type Prior Authorization

Page 437

Approval Criteria

1 - All of the following:

1.1 For symptoms of abrupt opioid withdrawal.

AND

1.2 Opioids have been discontinued.

AND

1.3 One of the following:

1.3.1 History of failure, contraindication, or intolerance to clonidine.

1.3.2 Lucemyra was initiated in the inpatient setting. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may also apply. Background Lucemyra is a central alpha-2 adrenergic agonist indicated for mitigation of opioid withdrawal

Page 438 symptoms to facilitate abrupt opioid discontinuation in adults.

4 . References

1. Lucemyra prescribing information. WorldMeds, LLC. Louisville, KY. May 2018. 2. Gowing L, Farrell M, Ali R, White J. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database of Systemic Reviews 2016, Issue 5.

5 . Revision History

Date Notes

2/19/2021 Annual review. No changes to criteria.

Page 439 Lyrica CR (pregabalin) - Step Therapy

Prior Authorization Guideline

GL-75235 Lyrica CR (pregabalin) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 1/1/2008 P&T Revision Date: 09/18/2019 ; 9/16/2020

1 . Indications Drug Name: Lyrica CR (pregabalin) Neuropathic pain FDA approved for neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia.

2 . Criteria

Product Name: Lyrica CR* [a] Approval Length 12 month(s) Guideline Type Step Therapy

Page 440 Approval Criteria

1 - Both of the following:

1.1 Diagnosis of neuropathic pain and history of failure, contraindication, or intolerance to two of the following medications (Document date of trial):

• gabapentin (generic Neurontin) • duloxetine (generic Cymbalta) • One (1) tricyclic antidepressant (e.g., amitriptyline), (Document Drug name)

AND

1.2 History of failure, contraindication, or intolerance to pregabalin (generic Lyrica) immediate release capsules or solution (Document date of trial and reason for failure)

2 - All other diagnoses (not specified above) and history of failure, contraindication or intolerance to BOTH of the following: (Document the diagnosis and ensure that the diagnosis is not associated with nerve pain which would require review as neuropathic pain. (Document date of trial)).

• gabapentin (generic Neurontin) • pregabalin (generic Lyrica) immediate release capsules or solution

Notes *Lyrica CR is typically excluded from coverage [a] State mandates may apply. Any federal regulatory requirements and the member specific b enefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background:

Lyrica CR (pregabalin) tablets are FDA approved for neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Lyrica CR is not approved for partial onset seizures or fibromyalgia as clinical trials failed to demonstrate efficacy for these indications. The National Comprehensive Cancer Network recognizes antiepileptic drugs,

Page 441 including gabapentin and Lyrica for treatment of chemotherapy induced peripheral neuropathy.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. If the member has evidence of Lyrica Capsules or Solution and an antiepileptic drug in the claims history, then Lyrica Capsules or Solution will automatically process.

Additional Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may also be in place.

4 . References

1. Lyrica CR [Prescribing Information]. New York, NY: Pfizer Inc.; June 2020. 2. Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice Parameter: Treatment of postherpetic neuralgia: An evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63(6):959-65. 3. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011; 76(20):1758-1765. 4. Tesfaye S, Boulton AJM, Dyck PJ et al. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. Diabetes Care. 2010;33(10):2285-93. 5. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan. Endocr Pract. 2011;17(Suppl 2):1-53. 6. http://www.uptodate.com/contents/initial-treatment-of-fibromyalgia-in-adults#H95200969. 7. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014 Apr 16;311(15):1547-55 8. Fitzcharles MA, et al. National Fibromyalgia Guideline Advisory Panel. 2012 Canadian guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag. 2013;18(3):119-126. 9. Bandelow B, et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive – compulsive disorder and posttraumatic stress disorder in primary care. Int J Psych Clin Practice. 2012; 16:77-84.

5 . Revision History

Page 442 Date Notes

10/13/2020 Annual review. Updated references.

Page 443 MEDcDUR - Opioid Overutilization Cumulative Drug Utilization Review Criteria (including individual long-acting opioid supply limits)

Prior Authorization Guideline

GL-88903 MEDcDUR - Opioid Overutilization Cumulative Drug Utilization Review Criteria (including individual long-acting opioid supply limits)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 8/19/2016 P&T Revision Date: 04/17/2019 ; 04/15/2020 ; 5/21/2021

1 . Criteria

Product Name: Individual Long-Acting Supply Limits Diagnosis Cancer or End of Life (defined as a < 2 year life expectancy) related pain for individual long-acting supply limits Approval Length 24 month(s) Guideline Type MEDcDUR

Approval Criteria

Page 444 1 - Coverage will be approved based on the following criteria:

1.1 Patient requires treatment with opioids due to active cancer diagnosis or end of life related pain (document cancer diagnosis or for end of life, expectancy of less than 2 years.) Notes Authorization for cancer or end of life pain will be issued for 24 months for a quantity of 9999 to prevent further disruption in therapy if the patie nt’s dose is increased. If the patient is currently taking a high dose opio id regimen where the supply limit is exceeded and does not meet the a uthorization criteria requirements for approval, a denial will be issued a nd a transition authorization of 90 days may be issued one time up to t he current quantity with up to one additional transition authorization (tot al of 2 transition authorizations).

Product Name: Individual Long-Acting Supply Limits Diagnosis Non-cancer and Non-End of Life Pain for individual long-acting supply limits Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type MEDcDUR

Approval Criteria

1 - Prescriber attests to ALL of the following:

AND

2 - The opioid regimen is not being used in combination with buprenorphine containing products for opioid dependence.

AND

3 - Treatment goals are defined and include estimated duration of treatment (must document treatment goals).

Page 445 AND

4 - Patient has been screened for underlying depression and/or anxiety. If applicable, any underlying conditions have been or will be addressed.

AND

5 - Document BOTH of the following:

• The total daily desired morphine milligram equivalent requested for the patient • The diagnosis associated with the need for pain management

AND

6 - Both of the following

• Patient has tried and failed non-opioid pain medication (document drug name and date of trial) • Have used opioid medications in lower doses and did not adequately control pain (document drug regimen or MME and dates of therapy)

Notes Authorization will be issued for 6 months up to the maximum ceiling lim it. If the patient is currently taking a high dose opioid regimen where th e supply limit is exceeded and does not meet the authorization criteria r equirements for approval, a denial will be issued and a transition autho rization of 90 days may be issued one time up to the current quantity wi th up to one additional transition authorization (total of 2 transition auth orizations).

Approval Criteria

Page 446 1 - Prescriber attests to ALL of the following:

AND

2 - The opioid regimen is not being used in combination with buprenorphine containing products for opioid dependence.

AND

3 - Document rationale for not tapering or discontinuing opioid if treatment goals are not being met.

AND

4 - Documented meaningful improvement in pain and function when assessed against treatment goals (Document improvement in function or pain score improvement).

AND

5 - Document both of the following

• The total daily desired morphine milligram equivalent requested for the patient • The diagnosis associated with the need for pain management

Product Name: Cumulative MMELIMIT^

Page 447 Diagnosis Cancer or End of Life (defined as a < 2 year life expectancy) related pain for MMELIMIT Approval Length 24 month(s) Guideline Type MEDcDUR

Approval Criteria

1 - Cumulative doses exceeding 180 morphine milligram equivalents (MME) will be approved based on the following criteria:

1.1 Patient is being treated for active cancer diagnosis or end of life related pain (document cancer diagnosis or for end of life, expectancy of less than 2 years.) Notes Authorization for cancer or end of life pain will be issued for 24 months for an MME of 9999 to prevent further disruption in therapy if the patien t’s dose is increased. If the patient is currently taking a high dose opioi d regimen where the MME exceeds 180 and does not meet the authori zation criteria requirements for cumulative opioid overutilization, a deni al will be issued and a transition authorization of 90 days may be issue d one time up to the current MME with up to one additional transition a uthorization (total of 2 transition authorizations). A transition authorizati on should not be granted to patients currently at or below the 180 MME threshold. ^ MMELIMIT refers to Cumulative MME of 180 *If in Ohio, p rescribers should reference the Ohio Guidelines created by the Govern or’s Cabinet Opiate Action Team when the dose exceeds 80 MME.

Product Name: Cumulative MMELIMIT^ Diagnosis Non-cancer and Non-End of Life Pain for MMELIMIT Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type MEDcDUR

Approval Criteria

1 - Required to meet all criteria for Non-cancer and Non-End of Life Pain for individual long- acting supply limits (Initial Authorization) Notes Authorization will be issued for 6 months up to the current requested M ME plus 90 MME up to a maximum of 990. If the patient is currently tak ing a high dose opioid regimen where the MME exceeds 180 and does not meet the authorization criteria requirements for cumulative opioid o verutilization, a denial will be issued and a transition authorization of 90 days may be issued one time up to the current MME with up to one ad

Page 448 ditional transition authorization (total of 2 transition authorizations). A tr ansition authorization should not be granted to patients currently at or b elow the 180 MME threshold. ^ MMELIMIT refers to Cumulative MME o f 180 *If in Ohio, prescribers should reference the Ohio Guidelines crea ted by the Governor’s Cabinet Opiate Action Team when the dose exc eeds 80 MME.

Product Name: Cumulative MMELIMIT^ Diagnosis Non-cancer and Non-End of Life Pain for MMELIMIT Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type MEDcDUR

Approval Criteria

1 - Required to meet all criteria for Non-cancer and Non-End of Life Pain for individual long- acting supply limits (Reauthorization) Notes Authorization will be issued for 6 months up to the current requested M ME plus 90 MME up to a maximum of 990. If the patient is currently tak ing a high dose opioid regimen where the MME exceeds 180 and does not meet the authorization criteria requirements for cumulative opioid o verutilization, a denial will be issued and a transition authorization of 90 days may be issued one time up to the current MME with up to one ad ditional transition authorization (total of 2 transition authorizations). A tr ansition authorization should not be granted to patients currently at or b elow the 180 MME threshold. ^ MMELIMIT refers to Cumulative MME o f 180 *If in Ohio, prescribers should reference the Ohio Guidelines crea ted by the Governor’s Cabinet Opiate Action Team when the dose exc eeds 80 MME.

2 . Background

Clinical Practice Guidelines

The Center for Disease Control (CDC): The Center for Disease Control (CDC) recommends that clinicians should prescribe the lowest effective dosage when opioids are started. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to 50 morphine equivalent doses (MME) or more per day, and should avoid increasing dosage to 90 MME or more per

Page 449 day or carefully justify a decision to titrate dosage to 90 MME or more per day.

According to the CDC, if a patient’s opioid dosage for all sources of opioids combined reaches or exceeds 50 MME per day, clinicians should implement additional precautions, including increased frequency of follow-up and considering offering naloxone. Clinicians should avoid increasing opioid dosages to 90 MME or more per day or should carefully justify a decision to increase dosage to 90 MME or more per day based on individualized assessment of benefits and risks and weighing factors such as diagnosis, incremental benefits for pain and function relative to harms as dosages approach 90 MME per day, other treatments and effectiveness, and recommendations based on consultation with pain specialists. If patients do not experience improvement in pain and function at 90 MME or more per day, or if there are escalating dosage requirements, clinicians should discuss other approaches to pain management, consider working with patients to taper opioids to a lower dosage, consider discontinuation of some or all opioids, and evaluate patients for opioid use disorder

Benefit/Coverage/Program Information

Additional Clinical Programs:

Medical Necessity and Step Therapy may also be in place.

^ MMELIMIT refers to Cumulative MME of 180 ** Ceiling limit is based on dose optimization and a maximum of 240 MME Supply Limit Grid:

*If in Ohio, prescribers should reference the Ohio Guidelines created by the Governor’s Cabinet Opiate Action Team when the dose exceeds 80 MME.

Supply Lim Drugs Strength CDC Max MME (90 Supply Limit/Month Supply Limit it MME equivalent*) Ceiling Limit for Gri Non-Cancer/ d: End of Life Pain**

morphine sulfate 90 mg/day 31 31 (1/day) controlled-release

Page 450 (generic Avinza) 30 mg morphine sulfate 90 mg/day 31 31 (1/day) controlled-release (generic Avinza) 45 mg morphine sulfate 90 mg/day 31 31 (1/day) controlled-release (generic Avinza) 60 mg morphine sulfate 90 mg/day 31 93 (3/day) controlled-release (generic Avinza) 75 mg morphine sulfate 90 mg/day 31 62 (2/day) controlled-release (generic Avinza) 90 mg morphine sulfate 90 mg/day 0 62 (2/day) controlled-release (generic Avinza) 120 mg methadone 10mg 22.5 mg/day 62 186 (6/day) methadone 5 mg 22.5 mg/day 124 124 tablets (4/day)

Duragesic 12 50 mcg q 72 hrs (1/2 15 15 (0.5/day) mcg/hr patch/day equivalent)

Duragesic 25 50 mcg q 72 hrs (1/2 15 15 (0.5/day) mcg/hr patch/day equivalent)

Duragesic 50 50 mcg q 72 hrs (1/2 10 15 (0.5/day) mcg/hr patch/day equivalent)

Duragesic 75 50 mcg q 72 hrs (1 10 10 (0.33/day) mcg/hr patch/day equivalent)

Duragesic 100 50 mcg q 72 hrs (1 10 10 (0.33/day)

Page 451 mcg/hr patch/day equivalent) hydromorphone 24 mg/day 31 31 (1/day) extended release 8 mg hydromorphone 24 mg/day 62 62 (2/day) extended release 12 mg hydromorphone 24 mg/day 31 93 (3/day) extended release 16 mg hydromorphone 24 mg/day 0 31 (1/day) extended release 32 mg

Fentanyl Patch 37.5 50 mcg q 72 hrs (1/2 10 15 (0.5/day) mcg/hr^ patch/day equivalent)

Fentanyl Patch 62.5 50 mcg q 72 hrs (1 10 15 (0.5/day) mcg/hr^ patch/day equivalent)

Fentanyl Patch 87.5 50 mcg q 72 hrs (1 10 10 (0.33/day) mcg/hr^ patch/day equivalent)

Hysingla ER 20 mg 90 mg/day 31 31 (1/day)

Hysingla ER 30 mg 90 mg/day 31 31 (1/day)

Hysingla ER 40 mg 90 mg/day 31 31 (1/day)

Hysingla ER 60 mg 90 mg/day 31 31 (1/day)

Hysingla ER 80 mg 90 mg/day 31 93 (3/day)

Hysingla ER 100 90 mg/day 0 62 (2/day) mg

Hysingla ER 120 90 mg/day 0 62 (2/day) mg morphine sulfate 90 mg/day 62 62 (2/day) sustained-release capsule (generic Kadian) 10 mg

Page 452 morphine sulfate 90 mg/day 62 62 (2/day) sustained-release capsule (generic Kadian) 20 mg morphine sulfate 90 mg/day 62 62 (2/day) sustained-release capsule (generic Kadian) 30 mg morphine sulfate 90 mg/day 62 62 (2/day) sustained-release capsule (generic Kadian) 40 mg morphine sulfate 90 mg/day 31 62 (2/day) sustained-release capsule (generic Kadian) 50 mg morphine sulfate 90 mg/day 31 62 (2/day) sustained-release capsule (generic Kadian) 60 mg morphine sulfate 90 mg/day 31 62 (2/day) sustained-release capsule (generic Kadian) 70 mg morphine sulfate 90 mg/day 31 93 (3/day) sustained-release capsule (generic Kadian) 80 mg morphine sulfate 90 mg/day 0 62 (2/day) sustained-release capsule (generic Kadian) 100 mg morphine sulfate 90 mg/day 0 31 (1/day) sustained-release capsule (generic Kadian) 130 mg morphine sulfate 90 mg/day 0 31 (1/day) sustained-release capsule (generic Kadian) 150 mg

Page 453 morphine sulfate 90 mg/day 0 31 (1/day) sustained-release capsule (generic Kadian) 200 mg

Methadone 10/5 mL 22.5 mg/day 350 mL 930mL (30 mL/day)

Methadone 5/5mL 22.5 mg/day 700 mL 1860 mL (60 mL/ day)

Methadone 10/1 mL 22.5 mg/day 186 mL 186 mL (6 mL/day)

Methadone 40 mg 22.5 mg/day 45 tablets 45 tablets (1.5 tablet for oral tablets/day) suspension

MS Contin 15 mg 90 mg/day 93 93 (3/day)

MS Contin 30 mg 90 mg/day 93 93 (3/day)

MS Contin 60 mg 90 mg/day 0 124 (4/day)

MS Contin 100 mg 90 mg/day 0 62 (2/day)

MS Contin 200 mg 90 mg/day 0 31 (1/day)

Nucynta ER 50 mg 225 mg/day 62 62 (2/day)

Nucynta ER 100 225 mg/day 62 62 (2/day) mg

Nucynta ER 150 225 mg/day 0 93(3/day) mg

Nucynta ER 200 225 mg/day 0 62 (2/day) mg

Nucynta ER 250 225 mg/day 0 62 (2/day) mg

Oxymorphone ER 5 30 mg/day 62 62 (2/day) mg

Oxymorphone ER 30 mg/day 62 62 (2/day) 7.5 mg

Oxymorphone ER 30 mg/day 62 62 (2/day) 10 mg

Oxymorphone ER 30 mg/day 62 62 (2/day)

Page 454 15 mg

Oxymorphone ER 30 mg/day 0 62 (2/day) 20 mg

Oxymorphone ER 30 mg/day 0 62 (2/day) 30 mg

Oxymorphone ER 30 mg/day 0 62 (2/day) 40 mg

OxyContin/ 60 mg/day 62 62 (2/day) oxycodone extended-release authorized generic 10 mg

OxyContin/ 60 mg/day 62 62 (2/day) oxycodone extended-release authorized generic 15 mg

OxyContin/ 60 mg/day 62 62 (2/day) oxycodone extended-release authorized generic 20 mg

OxyContin/ 60 mg/day 62 62 (2/day) oxycodone extended-release authorized generic 30 mg

OxyContin/ 60 mg/day 0 62 (2/day) oxycodone extended-release authorized generic 40 mg

OxyContin/ 60 mg/day 0 62 (2/day) oxycodone extended-release authorized generic 60 mg

OxyContin/ 60 mg/day 0 62 (2/day) oxycodone extended-release

Page 455 authorized generic 80 mg

Xtampza ER 9 mg 54 mg/day 62 62 (2/day)

Xtampza ER 13.5 54 mg/day 62 62 (2/day) mg

Xtampza ER 18 mg 54 mg/day 62 62 (2/day)

Xtampza ER 27 mg 54 mg/day 62 155 (5/day)

Xtampza ER 36 mg 54 mg/day 0 124 (4/day)

Zohydro ER 10 mg 90 mg/day 62 62 (2/day)

Zohydro ER 15 mg 90 mg/day 62 62 (2/day)

Zohydro ER 20 mg 90 mg/day 62 62 (2/day)

Zohydro ER 30 mg 90 mg/day 62 62 (2/day)

Zohydro ER 40 mg 90 mg/day 62 186 (6/day)

Zohydro ER 50 mg 90 mg/day 0 124 (4/day)

3 . References

1. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016. JAMA. Published online March 15, 2016.

4 . Revision History

Page 456 Date Notes

6/30/2021 Removed products no longer on the market. Revised provider attestati on. Added requirements for documentation of treatment goals and scre ening for underlying depression and anxiety. Administrative changes a nd references updated.

Page 457 Meglitinides and Meglitinide Combination Agents

Prior Authorization Guideline

GL-10604 Meglitinides and Meglitinide Combination Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 2/17/2009; CPS Revision Date: 4/8/2014; According to Texas State Law, all diabetic medications used for the treatment of diabetes shall be covered.

1 . Indications Drug Name: PrandiMet (repaglinide/metformin) Type 2 Diabetes Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a meglitinide and metformin HCl or who have inadequate glycemic control on a meglitinide alone or metformin HCl alone.

2 . Criteria

Page 458 Product Name: PrandiMet Guideline Type Step Therapy

Approval Criteria

1 - History of metformin [2,3,4]

3 . References

1. PrandiMet Prescribing Information. Novo Nordisk Inc. April 2012 2. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2014;37(Suppl):1:S14-S80 3. AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19 (No. 2) 4. Inzucchi SE, et al; Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), Diabetologia 2012;55:1577-96 5. Prandin Prescribing Information. Novo Nordisk. September 2011.

Page 459 Migraine Quantity Limit

Prior Authorization Guideline

GL-87397 Migraine Quantity Limit

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 5/19/2016 P&T Revision Date: 03/18/2020 ; 03/17/2021

1 . Indications Drug Name: Amerge (naratriptan), Frova (frovatriptan), Imitrex (sumatriptan) tablets and nasal spray, Onzetra (sumatriptan), Relpax (eletriptan), Tosymra (sumatriptan), Zembrace SymTouch (sumatriptan), Zomig (zolmitriptan) tablets, Zomig-ZMT (zolmitriptan) Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: Safety and effectiveness of respective triptan therapy have not been established for cluster headache (not applicable to Zembrace SymTouch). Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with therapy, reconsider the diagnosis of migraine before therapy is administered to treat any subsequent attacks. Therapy is not indicated for the prevention of migraine attacks.

Drug Name: Axert (almotriptan) Migraine Headaches Indicated for the acute treatment of migraine attacks in adults with a history of migraine with or without aura. Indicated for the acute treatment of migraine headache pain in adolescents age 12 to 17 years with a history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated). Important Limitations: Only use where a clear

Page 460 diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Axert, the diagnosis of migraine should be reconsidered before Axert is administered to treat any subsequent attacks. In adolescents age 12 to 17 years, efficacy of Axert on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. Axert is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of Axert have not been established for cluster headache which is present in an older, predominantly male population.

Drug Name: Maxalt (rizatriptan), Maxalt-MLT (rizatriptan) Migraine headaches Indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old. Limitations of Use: Maxalt should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with Maxalt, the diagnosis of migraine should be reconsidered before Maxalt is administered to treat any subsequent attacks. Maxalt is not indicated for use in the management of hemiplegic or basilar migraine. Maxalt is not indicated for the prevention of migraine attacks. Safety and effectiveness of Maxalt have not been established for cluster headache.

Drug Name: Migranal (dihydroergotamine mesylate) Migraine Headaches Indicated for the acute treatment of migraine headaches with or without aura. Not intended for the prophylactic therapy of migraine or for the management of hemiplegic or basilar migraine.

Drug Name: Treximet (sumatriptan/naproxen) Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age or older. Limitations of Use: Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with Treximet, reconsider the diagnosis of migraine before Treximet is administered to treat any subsequent attacks. Treximet is not indicated for the prevention of migraine attacks. Safety and effectiveness of Treximet have not been established for cluster headache.

Drug Name: Zomig (zolmitriptan) nasal spray Migraine Headaches Indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older. Limitations of Use: Only use Zomig if a clear diagnosis of migraine has been established. If a patient has no response to Zomig treatment for the first migraine attack, reconsider the diagnosis of migraine before Zomig is administered to treat any subsequent attacks. Zomig is not indicated for the prevention of migraine attacks. Safety and effectiveness of Zomig have not been established for cluster headache. Not recommended in patients with moderate or severe hepatic impairment.

Drug Name: D.H.E. 45 (dihydroergotamine mesylate) injection Migraine Headache Indicated for the acute treatment of migraine headaches with or without

Page 461 aura.

Cluster Headaches Indicated for acute treatment of cluster headache episodes.

Drug Name: Imitrex (sumatriptan) injection Migraine Headache Indicated in adults for the acute treatment of migraine, with or without aura. Limitations of Use: Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine headache attack treated with Imitrex injection, reconsider the diagnosis before Imitrex injection is administered to treat any subsequent attacks. Imitrex injection is not indicated for the prevention of migraine headache attacks.

Cluster Headaches Indicated in adults for the acute treatment of cluster headache. Limitations of Use: Use only if a clear diagnosis of cluster headache has been established. If a patient has no response to the first cluster headache attack treated with Imitrex injection, reconsider the diagnosis before Imitrex injection is administered to treat any subsequent attacks. Imitrex injection is not indicated for the prevention of cluster headache attacks.

2 . Criteria

Product Name: Brand Amerge, Generic naratriptan, Brand Axert, Generic almotriptan, Brand D.H.E. 45, Generic dihydroergotamine mesylate injection, Brand Frova, Generic frovatriptan, Brand Imitrex, Generic sumatriptan, Brand Maxalt, Generic rizatriptan, Brand Migranal, Generic dihydroergotamine mesylate nasal spray, Onzetra, Brand Relpax, Generic eletriptan, Sumavel DosePro, Tosymra, Brand Treximet, Generic sumatriptan/naproxen, Zembrace SymTouch, Brand Zomig, Generic zolmitriptan, or Brand Zolmitriptan nasal spray Approval Length 12 month(s) Guideline Type Quantity Limit

Approval Criteria

1 - Diagnosis of one of the following:

• Acute migraines with or without aura • Cluster headaches

AND

2 - Prescribed by or in consultation with one of the following:

Page 462 • Neurologist • Pain management specialist

AND

3 - Patient is experiencing 2 or more headaches per month [10-12]

AND

4 - Patient will not be treating 15 or more headache days per month

AND

5 - Currently receiving prophylactic therapy with at least one of the following: [A]

• Antidepressants • Anticonvulsants • Beta-blockers

AND

6 - Not used in combination with another triptan or ergotamine-containing product

AND

7 - One of the following: [B]

7.1 Higher dose or quantity is supported in the Dosage and Administration section of the manufacturer’s prescribing information

7.2 Higher dose or quantity is supported by one of the following compendia:

• American Hospital Formulary Service Drug Information

Page 463 • Micromedex DRUGDEX System

3 . Endnotes

A. American Academy of Neurology (AAN)-recommended first-line agents for the prevention of migraine headache are atenolol, metoprolol, nadolol, propranolol, timolol, amitriptyline, venlafaxine, topiramate, and divalproex sodium. [10-12, 17] B. Published biomedical literature may be used as evidence to support safety and additional efficacy at higher than maximum doses for the diagnosis provided.

4 . References

1. Amerge Prescribing Information. GlaxoSmithKline. Research Triangle Park, NC. October 2020. 2. Axert Prescribing Information. Janssen Pharmaceuticals, Inc. Titusville, NJ. May 2017. 3. Frova Prescribing Information. Endo Pharmaceuticals Inc. Malvern, PA. August 2018. 4. Imitrex Tablets Prescribing Information. GlaxoSmithKline. Research Triangle Park, NC. September 2020. 5. Imitrex Nasal Spray Prescribing Information. GlaxoSmithKline. Research Triangle Park, NC. December 2017. 6. Imitrex Injection Prescribing Information. GlaxoSmithKline. Research Triangle Park, NC. September 2020. 7. Maxalt/Maxalt MLT Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. September 2020. 8. Migranal Prescribing Information. Valeant Pharmaceuticals North America LLC. Bridgewater, NJ. July 2019. 9. Relpax Prescribing Information. Roerig. New York, NY. March 2020. 10. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345. 11. Silberstein SD, Holland S, Freitag F, et al. Erratum to: evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2013;80(9):871. 12. Snow V, Weiss K, Wall EM, Mottur-Pilson C; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840-9. 13. Onzetra Xsail Prescribing Information. Currax Pharmaceuticals LLC. Morristown, NJ. December 2019. 14. Treximet Prescribing Information. Currax Pharmaceuticals LLC. Morristown, NJ. November 2019.

Page 464 15. Zomig/Zomig ZMT Prescribing Information. Amneal Pharmaceuticals LLC. Bridgewater, NJ. May 2019. 16. Zomig Nasal Spray Prescribing Information. Amneal Pharmaceuticals LLC. Bridgewater, NJ. May 2019. 17. D.H.E. 45 Prescribing Information. Bausch Health US, LLC. Bridgewater, NJ. November 2019. 18. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN Guidelines for Prevention of Episodic Migraine: A Summary and Comparison with Other Recent Clinical Practice Guidelines. Headache 2012;52:930-945. 19. Zembrace SymTouch Prescribing Information. Promius Pharma, LLC. Princeton, NJ. June 2019. 20. Tosymra Prescribing Information. Promius Pharma, LLC. Princeton, NJ. January 2019.

5 . Revision History

Date Notes

5/21/2021 Addition of EHB formulary to guideline, no changes to criteria

Page 465 Minocycline extended-release tablet (generic Solodyn), Minolira (minocycline extended-release tablet), Solodyn (minocycline extended-release tablet), Ximino (minocycline extended-release capsule)

Prior Authorization Guideline

GL-86062 Minocycline extended-release tablet (generic Solodyn), Minolira (minocycline extended-release tablet), Solodyn (minocycline extended-release tablet), Ximino (minocycline extended-release capsule)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 8/18/2017 P&T Revision Date: 02/14/2020 ; 2/19/2021

1 . Indications Drug Name: Minolira, Solodyn and Ximino Severe acne vulgaris Indicated to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older.

2 . Criteria

Product Name: Minocycline Extended-Release (generic Solodyn) [A] Approval Length 3 month(s) Guideline Type Non Formulary

Page 466

Approval Criteria

1 - Diagnosis of moderate to severe inflammatory acne vulgaris

AND

2 - One of the following:

2.1 Submission of medical records (e.g. chart notes) documenting an inadequate response to a four week trial of minocycline immediate-release capsule (generic Minocin)

2.2 Submission of medical records (e.g. chart notes) documenting an intolerance to minocycline immediate-release capsule (generic Minocin) which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction)

Product Name: Minolira, Solodyn and Ximino [A] Approval Length 3 month(s) Guideline Type Non Formulary

Approval Criteria

1 - Diagnosis of moderate to severe inflammatory acne vulgaris

AND

2 - One of the following:

2.1 Submission of medical records (e.g. chart notes) documenting an inadequate response to a four week trial of minocycline immediate-release capsule (generic Minocin)

2.2 Submission of medical records (e.g. chart notes) documenting an intolerance to

Page 467 minocycline immediate-release capsule (generic Minocin) which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction)

AND

3 - One of the following:

3.1 Submission of medical records (e.g. chart notes) documenting an inadequate response to a four week trial of minocycline extended-release (generic Solodyn)*

3.2 Submission of medical records (e.g. chart notes) documenting an intolerance to minocycline extended-release (generic Solodyn)* which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. dose reduction)

3 . Background

Benefit/Coverage/Program Information

Background:

Systemic antibiotics are an option for the treatment of acne. They are indicated for use in moderate to severe inflammatory acne and should be used in combination with a topical retinoid, benzoyl peroxide, and/or a topical antibiotic.

Minolira, Solodyn and Ximino are indicated to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older. They did not demonstrate any effect on non-inflammatory acne lesions. The safety of Minolira, Solodyn and Ximino has not been established beyond 12 weeks of use.

This program requires a member to try minocycline immediate-release capsule (generic Minocin) and minocycline extended-release (generic Solodyn)* prior to receiving coverage for Minolira, Solodyn or Ximino. In addition, it requires a member to try minocycline immediate- release capsule (generic Minocin) prior to receiving coverage for minocycline extended-release tablet (generic Solodyn)*.

Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and

Page 468 reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

*Prior Authorization may be required

4 . Endnotes

A. State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may apply.

5 . References

1. Minolira [package insert]. Charleston, SC: EPI Health, LLC; June 2018. 2. Solodyn [package insert]. Valeant Pharmaceuticals North America LLC. Bridgewater, NJ. September 2017. 3. Ximino [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; April 2017. 4. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016 Feb 15.

6 . Revision History

Date Notes

4/22/2021 02/2021 P&T - Annual review. Updated references

Page 469 Mirvaso (brimonidine gel), Rhofade (oxymetazoline cream)

Prior Authorization Guideline

GL-88397 Mirvaso (brimonidine gel), Rhofade (oxymetazoline cream)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 5/15/2020 P&T Revision Date: 5/21/2021

1 . Indications Drug Name: Mirvaso (brimonidine gel), Rhofade (oxymetazoline cream) Rosacea Indicated for the topical treatment of persistent (nontransient) erythema of rosacea in adults.

2 . Criteria

Product Name: Mirvaso and Rhofade Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Page 470

Approval Criteria

1 - Diagnosis of rosacea

AND

2 - Treatment of persistent facial erythema

Product Name: Mirvaso and Rhofade Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to therapy.

3 . Background

Benefit/Coverage/Program Information

Background: Mirvaso® (brimonidine) 0.33% topical gel and Rhofade® (oxymetazoline) 1% topical cream are alpha-adrenergic agonists indicated for the topical treatment of persistent (nontransient) erythema of rosacea in adults Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place • Step Therapy may be in place

4 . References

Page 471 1. Mirvaso [package insert]. Fort Worth, TX; Galderma Laboratories, L.P.; June 2018. 2. Rhofade [package insert]. Charleston SC: EPI Health; November 2019.

5 . Revision History

Date Notes

6/15/2021 Annual review. Updated references.

Page 472 Motegrity (prucalopride) - PA/Med Nec

Prior Authorization Guideline

GL-89372 Motegrity (prucalopride) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 6/27/2019 P&T Revision Date: 06/17/2020 ; 6/16/2021

1 . Indications Drug Name: Motegrity Chronic Idiopathic Constipation Indicated for the treatment of chronic idiopathic constipation in adults.

2 . Criteria

Product Name: Motegrity (prucalopride) [a] Diagnosis Chronic Idiopathic Constipation Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 473

Approval Criteria

1 - Diagnosis of chronic idiopathic constipation

AND

2 - History of failure, contraindication or intolerance to one OTC medication used for the treatment of constipation (document duration of trial)

AND

3 - One of the following criteria:

3.1 History of failure, contraindication, or intolerance to Linzess

Product Name: Motegrity (prucalopride) [a] Diagnosis Chronic Idiopathic Constipation Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Motegrity therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl

Page 474 y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place. • Notification/Prior Authorization may be in place Background:

Motegrity (prucalopride) is indicated for the treatment of chronic idiopathic constipation in adults. Physicians and patients should periodically assess the need for continued treatment with Motegrity. Linzess (linaclotide) is indicated for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation in adults aged 18 years and older. Linzess has a black box warning regarding the risk of serious dehydration in pediatric patients less than 17 years of age, and use of Linzess should be avoided in pediatric patients.

This program is intended to encourage the use of lower cost alternatives and requires a member to try an over-the-counter medication (OTC) for constipation and Linzess before providing coverage for Motegrity.

4 . References

1. Linzess [package insert]. Madison, NJ: Allergan USA, Inc.; April 2021. 2. Motegrity [package insert]. Lexington, MA: Takeda Pharmaceuticals America, Inc.; November 2020.

5 . Revision History

Date Notes

7/2/2021 Annual review. Updated references.

Page 475

Page 476 Movantik (naloxegol) - PA/Med Nec

Prior Authorization Guideline

GL-89369 Movantik (naloxegol) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 7/18/2018 P&T Revision Date: 08/14/2020 ; 6/16/2021

1 . Indications Drug Name: Movantik (naloxegol) Opioid-induced constipation (OIC) Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

2 . Criteria

Product Name: Movantik (naloxegol) [a],* Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 477 Guideline Type Prior Authorization

Approval Criteria

1 - ONE of the following:

1.1 Diagnosis of opioid-induced constipation with chronic, non-cancer pain

1.2 Diagnosis of opioid-induced constipation in patients with chronic pain related to prior cancer diagnosis or cancer treatment who do not require frequent (e.g., weekly) opioid dosage escalation

AND

2 - History of failure, contraindication or intolerance to BOTH of the following:

2.1 An OTC laxative (document name and date tried)

AND

2.2 Symproic Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Movantik is typically excluded from coverage

Product Name: Movantik (naloxegol) [a],* Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Movantik therapy

Page 478 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. *Movantik is typically excluded from coverage.

3 . Background

Benefit/Coverage/Program Information

Background:

Movantik (naloxegol) and Symproic (naldemedine) are opioid antagonists indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

This prior authorization program is intended to encourage the use of lower cost alternatives. This program requires a member to try over-the-counter (OTC) laxative therapy and Symproic before providing coverage for Movantik.

4 . References

1. Movantik [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP.; April 2020. 2. Symproic [package insert]. Raleigh, NC: BioDelivery Sciences International May 2020.

5 . Revision History

Date Notes

7/2/2021 Annual review. Updated references.

Page 479 Multaq (dronedarone)

Prior Authorization Guideline

GL-68915 Multaq (dronedarone)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2020 P&T Approval Date: 4/4/2015 P&T Revision Date: 06/17/2019 ; 6/17/2020

1 . Indications Drug Name: Multaq (dronedarone) Atrial fibrillation Indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation.

2 . Criteria

Product Name: Multaq Approval Length 12 month(s) Guideline Type Notification

Page 480 Approval Criteria

1 - One of the following:

1.1 All of the following criteria:

1.1.1 Diagnosis of a history of one of the following:

• Paroxysmal atrial fibrillation (AF) • Persistent AF defined as AF less than 6 months duration

AND

1.1.2 One of the following:

• Patient is in sinus rhythm • Patient is planned to undergo cardioversion to sinus rhythm

AND

1.1.3 Patient has none of the following:

• NYHA Class IV heart failure • Symptomatic heart failure with recent decompensation requiring hospitalization

1.2 For continuation of current therapy

3 . Background

Benefit/Coverage/Program Information

Background:

Multaq is an antiarrhythmic drug indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation.

Page 481

Multaq carries a black box warning for increased risk of death, stroke, and heart failure in patients with decompensated heart failure or permanent atrial fibrillation. It is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure, as Multaq doubles the risk of death in these patients. Multaq is also contraindicated in patients in atrial fibrillation who will not or cannot be cardioverted into normal sinus rhythm. In patients with permanent atrial fibrillation, Multaq doubles the risk of death, stroke and hospitalization for heart failure.

Patients currently on Multaq therapy will be allowed to remain on therapy.

4 . References

1. Multaq Prescribing Information. Sanofi Winthrop Industrie. Ambares, France. January 2017. 2. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):2246-2280.

5 . Revision History

Date Notes

7/7/2020 Annual review with no changes.

Page 482 Multisource Brand Anticonvulsants

Prior Authorization Guideline

GL-73070 Multisource Brand Anticonvulsants

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 2/15/2019 P&T Revision Date: 03/18/2020 ; 7/15/2020

1 . Criteria

Product Name: Lyrica, Onfi, Trileptal, Zonegran Diagnosis Epilepsy, Seizures and Status Epilepticus Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Both of the following:

Page 483 1.1 History of greater than or equal to a 4 week trial of the therapeutically equivalent generic (document date of trial)

AND

1.2 Documented history of an inadequate response to the therapeutically equivalent generic as evidenced by one of the following (document inadequate response):

• Change in seizure frequency from baseline • Breakthrough seizures not explained by medication noncompliance or significant provoking factor • Status epilepticus

2 - Documented history of intolerance to the therapeutically equivalent generic which is unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g., change timing of dosing, divide daily dose out for more frequent but smaller doses)

3 - Documented history of drug-resistant epilepsy (defined as the failure of two tolerated and appropriately chosen and used anti-epileptic drug schedules [as either mono-therapy or combination therapy] to achieve sustained seizure freedom) (document names of the two medications and dates of trials)

4 - Documented history of a high risk for seizure recurrence defined as one or more of the following:

• Identifiable brain disease • Mental retardation • Abnormal neurologic examination • Seizure onset after the first decade • Multiple seizure types • Poor initial response to treatment • Juvenile myoclonic epilepsy • Epileptiform discharges on electroencephalogram (EEG) • Family history of epilepsy • Hippocampal atrophy or abnormal hippocampal signal on magnetic resonance imaging

Page 484 (MRI)

Product Name: Onfi, Trileptal, Zonegran Diagnosis Other Indications (e.g. mania, bipolar disorder, migraine prophylaxis, neuropathy, postherpetic neuralgia) Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Both of the following:

1.1 History of greater than or equal to a 4 week trial of the therapeutically equivalent generic (document date of trial)

AND

1.2 Documented history of an inadequate response to the therapeutically equivalent generic (document inadequate response)

Product Name: Lyrica Diagnosis Other Indications (e.g. mania, bipolar disorder, migraine prophylaxis, neuropathy, postherpetic neuralgia) Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 485 Approval Criteria

1 - One of the following:

1.1 Diagnosis of neuropathic pain and history of failure, contraindication, or intolerance to two of the following medications (Document date of trial):

• gabapentin (generic Neurontin) • duloxetine (generic Cymbalta) • tricyclic antidepressant (e.g. amitriptyline)

1.2 All other diagnoses and history of failure, contraindication or intolerance to the following: (Document the diagnosis and ensure that the diagnosis is not associated with nerve pain which would require review as neuropathic pain. [Document date of trial]).

• gabapentin (generic Neurontin)

AND

2 - One of the following:

2.1 Both of the following:

• History of greater than or equal to 4-week trial of the therapeutically equivalent generic (document date of trial) • Documented history of an inadequate response to the therapeutically equivalent generic (document inadequate response)

2.2 Documented history of an intolerance to the therapeutically equivalent generic which was unable to be resolved with attempts to minimize the adverse effects where appropriate (e.g. change timing of dosing, divide daily dose out for more frequent but smaller doses)

Product Name: Lyrica, Onfi, Trileptal, Zonegran Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 486

Approval Criteria

1 - Documentation of positive clinical response to therapy

2 . Background

Benefit/Coverage/Program Information

Background:

This program requires a member to try the A-rated generic prior to receiving coverage for brand Lyrica, Onfi, Trileptal or Zonegran unless patient has a history of drug-resistant epilepsy or is at high risk of seizure recurrence.

Additional Clinical Rules:

3 . References

1. Trileptal [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2020. 2. Zonegran [package insert]. Dublin, Ireland: Concordia Pharmaceuticals Inc; April 2020. 3. Lyrica [package insert]. New York, NY: Pfizer Inc; April 2020. 4. Britton JW. Antiepileptic drug withdrawal: literature review. Mayo Clin Proc. 2002;77(12):1378. 5. Kwan P, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6);1069. 6. Talati R, et al. Effectiveness and Safety of Antiepileptic Medications in Patients with Epilepsy. Agency for Healthcare Research and Quality (US); December 2011. 7. Onfi [package insert]. Deerfield, IL: Lundbeck Pharmaceuticals LLC; June 2018.

4 . Revision History

Page 487 Date Notes

9/8/2020 7/2020 P&T - Addition of Onfi to criteria. Updated background and refe rences. Updated Lyrica criteria for non-seizure disorders to require trial and failure of step one medications based on indication.

Page 488 Mytesi (crofelemer)

Prior Authorization Guideline

GL-83003 Mytesi (crofelemer)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 2/19/2013 P&T Revision Date: 02/15/2019 ; 02/14/2020 ; 2/19/2021

1 . Indications Drug Name: Mytesi (crofelemer) HIV/AIDS anti-retroviral associated diarrhea Indicated for the symptomatic relief of non- infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy.

2 . Criteria

Product Name: Mytesi Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Page 489

Approval Criteria

1 - Diagnosis of HIV/AIDS associated diarrhea

AND

2 - Patient is on antiretroviral therapy

Product Name: Mytesi Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Mytesi therapy

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Background:

Mytesi (crofelemer) is an anti-diarrheal indicated for the symptomatic relief of non- infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy.1

4 . References

Page 490 1. Mytesi [package insert]. San Francisco, CA: Napo Pharmaceuticals, Inc; November 2020.

5 . Revision History

Date Notes

3/17/2021 Annual review. No change in clinical coverage. Updated reference.

Page 491 Nexletol (bempedoic acid) and Nexlizet (bempedoic acid/ezetimibe) - PA/Med Nec

Prior Authorization Guideline

GL-71838 Nexletol (bempedoic acid) and Nexlizet (bempedoic acid/ezetimibe) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/15/2020

P&T Revision Date:

1 . Indications Drug Name: Nexletol (bempedoic acid), Nexlizet (bempedoic acid/ezetimibe) Primary Hyperlipidemia Indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

2 . Criteria

Product Name: Nexletol [a], Nexlizet [a] Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 492 Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

• Heterozygous familial hypercholesterolemia (HeFH) • Atherosclerotic cardiovascular disease (ASCVD)

AND

2 - One of the following:

2.1 Patient has been receiving at least 12 consecutive weeks of high intensity statin therapy [i.e. atorvastatin 40-80 mg, rosuvastatin 20-40 mg] and will continue to receive a high intensity statin at maximally tolerated dose

2.2 Both of the following:

2.2.1 Patient is unable to tolerate high-intensity statin as evidenced by one of the following intolerable and persistent (i.e. more than 2 weeks) symptoms:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations < 10 times upper limit of normal [ULN])

AND

2.2.2 One of the following:

2.2.2.1 Patient has been receiving at least 12 consecutive weeks of moderate- intensity statin therapy [i.e. atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin ≥ 20 mg, pravastatin ≥ 40 mg, lovastatin 40 mg, Lescol XL (fluvastatin XL) 80 mg, fluvastatin 40 mg twice daily or Livalo (pitavastatin) ≥ 2 mg] and will continue to receive a moderate-intensity statin at maximally tolerated dose

Page 493 2.2.2.2 Patient has been receiving at least 12 consecutive weeks of low-intensity statin therapy [i.e. simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg, fluvastatin 20-40 mg, or Livalo (pitavastatin) 1 mg] statin therapy and will continue to receive a low-intensity statin at maximally tolerated dose

2.3 Patient is unable to tolerate low or moderate-, and high-intensity statins as evidenced by one of the following:

2.3.1 One of the following intolerable and persistent (i.e. more than 2 weeks) symptoms for low or moderate-, and high-intensity statins:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations < 10 times upper limit of normal [ULN])

2.3.2 Patient has a labeled contraindication to all statins as documented in medical records

2.3.3 Patient has experienced rhabdomyolysis or muscle symptoms with statin treatment with CK elevations > 10 times ULN

AND

3 - One of the following:

3.1 Documentation of one of the following LDL-C values while on maximally tolerated lipid lowering therapy for a minimum of at least 12 weeks within the last 120 days:

• LDL-C ≥ 100 mg/dL with ASCVD • LDL-C ≥ 130 mg/dL without ASCVD

3.2 Both of the following:

Page 494 3.2.1 Documentation of one of the following LDL-C values while on maximally tolerated lipid lowering therapy for a minimum of at least 12 weeks within the last 120 days:

• LDL-C between 70 mg/dL and 99 mg/dL with ASCVD • LDL-C between 100 mg/dL and 129 mg/dL without ASCVD

AND

3.2.2 Documentation of one of the following:

3.2.2.1 Patient has been receiving at least 12 consecutive weeks of ezetimibe (Zetia®) therapy as adjunct to maximally tolerated statin therapy

3.2.2.2 Patient has a history of contraindication, or intolerance to ezetimibe Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Nexletol [a], Nexlizet [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Both of the following:

• Documentation of a positive clinical response to therapy • Patient continues to receive statin at maximally tolerated dose (unless patient has documented inability to take statins)

Page 495

3 . Background

Benefit/Coverage/Program Information

Background:

Nexletol (bempedoic acid) and Nexlizet (bempedoic acid/ezetimibe) are indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

Additional Clinical Rules:

4 . References

1. Nexletol [package insert]. Ann Arbor, MI: Esperion Therapeutics, Inc; February 2020. 2. Nexlizet [package insert]. Ann Arbor, MI: Esperion Therapeutics, Inc; February 2020. 3. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-934. 4. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251:365-74. 5. ATP III Final Report PDF. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421. 6. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017; Suppl 2;23:1-87. 7. Lloyd-Jones D, Morris P, Ballantyne C, et al. 2017 Focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL- cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2017. 8. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood

Page 496 cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; DOI: 10.1161/CIR.0000000000000625.

5 . Revision History

Date Notes

8/18/2020 New program.

Page 497 Nocdurna (desmopressin acetate)- PA/Med Nec

Prior Authorization Guideline

GL-82998 Nocdurna (desmopressin acetate)- PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 5/18/2018 P&T Revision Date: 02/14/2020 ; 2/19/2021

1 . Indications Drug Name: Nocdurna (desmopressin acetate) nocturia due to nocturnal polyuria Indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void.

2 . Criteria

Product Name: Nocdurna [a] Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 498

Approval Criteria

1 - Diagnosis of nocturia due to nocturnal polyuria (as defined by nighttime urine production that exceeds one-third of the 24-hour urine production)

AND

2 - Patient wakes at least twice per night on a reoccurring basis to void

AND

3 - Documented serum sodium level is currently within normal limits of the normal laboratory reference range and has been within normal limits over the previous six months.

AND

4 - The patient has been evaluated for other medical causes and has either not responded to, tolerated, or has a contraindication to treatments for identifiable medical causes (e.g., overactive bladder, benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), elevated post-void residual urine, and heart failure)

AND

5 - Prescriber attests that the risks have been assessed and benefits outweigh the risks Notes a State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact coverage c riteria. Other policies and utilization management programs may apply.

Product Name: Nocdurna [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 499 Approval Criteria

1 - Documentation of positive clinical response to Nocdurna therapy

AND

2 - Patient has routine monitoring for serum sodium levels

AND

3 - Prescriber attests that the risks of hyponatremia have been assessed and benefits outweigh the risks Notes a State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact coverage c riteria. Other policies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background Nocdurna (desmopressin acetate) sublingual tablets are indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void. In clinical trials, nocturnal polyuria was defined as nighttime urine production exceeding one-third of the 24-hour urine production. Prior to initiating treatment with Nocdurna, patients should be evaluated for possible causes of nocturia and to optimize the treatment of underlying conditions that may be contributing to the nocturia.

Desmopressin should be avoided in older adults (those 65 or older) due to the risk of hyponatremia. This medication is included in the American Geriatrics Society Beers Criteria. Nocdurna have a Black Box Warning for hyponatremia listed in the FDA prescribing information. Nocdurna use is contraindicated in patients with hyponatremia or a history of hyponatremia, SIADH, eGFR <50 mL/min/1.7m2, uncontrolled hypertension, and New York Heart Association Class II – IV congestive heart failure. See package insert for full listing of contraindications and safety warnings.

Page 500

This prior authorization program is intended to ensure appropriate prescribing of Nocdurna prior to initiating therapy. Additional Clinical Rules

4 . References

1. Johnson, TM. Nocturia: Clinical presentation, evaluation and management in adults. O’Leary, MP, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on December 23, 2019.) 2. Nocdurna (desmopressin) sublingual tablets [package insert]. Ferring Pharmaceuticals Inc. Parsippany, NJ 07054. June 2018. 3. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015; 63(11):2227–2246

5 . Revision History

Date Notes

3/31/2021 Noctiva removed from the criteria since product has been discontinued .

Page 501 Non-Solid Oral Dosage Forms

Prior Authorization Guideline

GL-83123 Non-Solid Oral Dosage Forms

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 6/20/2018 P&T Revision Date: 08/16/2019 ; 12/18/2019 ; 02/14/2020 ; 09/16/2020 ; 12/16/2020 ; 2/19/2021

1 . Criteria

Product Name: Zegerid suspension[a] Approval Length 12 month(s) Guideline Type Non Formulary

Approval Criteria

1 - One of the following:

1.1 Patient is unable to ingest a solid dosage form (e.g., an oral tablet or capsule) due to one of the following:

Page 502 • age • oral/motor difficulties • dysphagia

1.2 Patient utilizes a feeding tube for medication administration

AND

2 - Patient has a history of trial and failure, intolerance or contraindication to BOTH of the following:

• Nexium suspension • Prevacid SoluTabs

Product Name: Alkindi Sprinkle, Carafate Suspension, Carospir, Drizalma Sprinkle, Epaned, Ezallor Sprinkle, Flolipid, Gloperba, Katerzia, Naprosyn suspension, Ozobax, Prograf Granules, Purixan, Qbrelis, Qdolo, Simvastatin oral suspension (authorized generic of Flolipid), Syndros, Tiglutik, Tirosint-Sol and Xatmep [a] Approval Length 12 month(s) Guideline Type Prior Authorization or Non Formulary

Approval Criteria

1 - One of the following:

1.1 Patient is unable to ingest a solid dosage form (e.g., an oral tablet or capsule) due to one of the following:

• age • oral/motor difficulties • dysphagia

Page 503

1.2 Patient utilizes a feeding tube for medication administration Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

2 . Background

Benefit/Coverage/Program Information

Background:

Coverage criteria outlined are for patients unable to ingest a solid oral dosage form.

Additional Clinical Rules:

3 . References

1. Epaned [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc. March 2020 2. Flolipid [package insert]. Brooksville, FL: Salerno Pharmaceuticals LP. June 2020. 3. Purixan [package insert]. Franklin, TN: Rare Disease Therapeutics, Inc. April 2020. 4. Qbrelis [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc. March 2020. 5. Syndros [package insert]. Chandler, AZ: Insys Therapeutics, Inc. September 2018. 6. Xatmep [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc; March 2020. 7. Zegerid [package insert]. Raleigh, NC: Salix Pharmaceuticals, Inc. September 2019. 8. Carospir [package insert]. Farmville, NC: CMP Pharma, Inc. August 2017. 9. Tiglutik [package insert]. Berwyn, PA: ITF Pharma, Inc. December 2019. 10. Naprosyn [package insert]. Atlanta, GA: Athena Bioscience LLC. July 2019. 11. Tirosint-Sol [package insert]. Pambio-Noranco, Switzerland: IBSA Institut Biochimique SA; June 2018. 12. Katerzia [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc; March 2020. 13. Prograf [package insert]. Northbrook, IL: Astellas Pharma US, Inc; July 2019.

Page 504 14. Ezallor Sprinkle [package insert]. Cranbury, NJ: Sun Pharmaceutical, Inc.; October 2020. 15. Gloperba [package insert]. Alpharetta, GA: Avion Pharmaceuticals, LLC.; February 2019. 16. Ozobax [package insert]. Athens, GA: Metacel Pharmaceuticals, LLC; May 2020. 17. Drizalma Sprinkle [package insert]. Cranbury, NJ: Sun Pharmaceuticals Industries, Inc; July 2020. 18. Carafate [package insert]. Madison, NJ: Allergan USA, Inc; June 2018. 19. Alkindi Sprinkle [package insert]. Baden-Wuerttemberg, Germany: Glatt Pharmaceuticals Services GmbH & Co; October 2020. 20. Qdolo [package insert]. Athens, GA: Athena Bioscience, LLC; September 2020.

4 . Revision History

Date Notes

3/18/2021 02/2021 P&T - Qdolo added to criteria.

Page 505 Non-steroidal Anti-Inflammatory Agents

Prior Authorization Guideline

GL-37299 Non-steroidal Anti-Inflammatory Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 11/18/2008; P&T Revision Date: 7/27/2016, 9/27/2017 **Effective 11/1/2017**

1 . Indications Drug Name: Sprix (ketorolac tromethamine) nasal spray Moderate to moderately severe pain Indicated in adult patients for the short term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level.

Drug Name: Tivorbex (indomethacin) capsules Mild to moderate pain Indicated for treatment of mild to moderate acute pain in adults.

Drug Name: Cambia (diclofenac) powder

Page 506 Migraine Indicated for the acute treatment of migraine attacks with or without aura in adults (18 years of age or older). Limitations of use: Cambia is not indicated for the prophylactic therapy of migraine. The safety and effectiveness of Cambia have not been established for cluster headache, which is present in an older, predominantly male population.

2 . Criteria

Product Name: Sprix nasal spray Approval Length 5 Days [A] Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to moderately severe pain

AND

2 - One of the following:

2.1 Trial and failure, contraindication, or intolerance to oral ketorolac* tablets

2.2 Patient is unable to take medications orally Notes *Ketorolac is recommended only for patients less than 65 years old. [B, C]

Product Name: Tivorbex*, Cambia* Guideline Type Step Therapy

Approval Criteria

1 - Trial and failure, contraindication, or intolerance to two of the following:

Page 507 • diclofenac or diclofenac ER • diflunisal • etodolac • fenoprofen • flurbiprofen • ibuprofen • indomethacin • ketoprofen • ketorolac • meclofenamate • meloxicam • nabumetone • naproxen • oxaprozin • piroxicam • sulindac • tolmetin

Notes *Per the American Geriatrics Society 2012 updated Beers criteria, chro nic use of NSAIDs, including indomethacin, is not recommended for pa tients greater than or equal to 65 years old unless other alternatives ar e not effective and patient can take gastroprotective agent (proton pum p inhibitor or misoprostol) [C]

3 . Endnotes

A. The total duration of use of Sprix alone or sequentially with other formulations of ketorolac (IM/IV or oral) must not exceed 5 days because of the potential for increasing the frequency and severity of adverse reactions associated with the recommended doses. Treat patients for the shortest duration possible, and do not exceed 5 days of therapy with Sprix. [21] B. This drug is included on the 2012 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults greater than or equal to 65 years old. [24] C. This drug is included on the 2013 Health Plan Employer Data and Information Set (HEDIS) list of high-risk medications in the elderly (greater than or equal to 65 years old) [25]

4 . References

1. Ponstel Prescribing Information. Shinogi Inc, September 2013. 2. Flector Patch Prescribing Information. King Pharmaceuticals. August 2011. 3. Naprelan Prescribing Information. Almatica Pharma, Inc., October 2013. 4. Solaraze Prescribing Information. PharmaDerm. December 2012.

Page 508 5. Zipsor Prescribing Information. Depomed. December 2012. 6. Hawkey C, Kahan A, Steinbruck, et al. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. Br J Rheumatol 1998;37:937-945. 7. Micklewright R, Lane S, Linley W, McQuade C, Thompson F, Maskrey N. Review article: NSAIDs, gastroprotection and cyclo-oxygenase-II-selective inhibitors. Aliment Pharmacol Ther 2003;17:321-332. 8. Dequeker J, Hawkey C, Kahan A, et al. Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the safety and efficacy large-scale evaluation of cox-inhibiting therapies (SELECT) trial in osteoarthritis. Br J Rheumatol 1998;37:946-951. 9. Schoenfeld P. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. Am J Med 1999;107(6A):48S-54S. 10. Ruperto N, Nikishina I, Pachanov ED, et al. A randomized, double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: short- and long-term efficacy and safety results. Arthritis Rheum 2005;52(2):563-572. 11. National Institute for Clinical Excellence. Guidance on the use of cyclo-oxygenase (Cox) II selective inhibitors, celecoxib, rofecoxib, meloxicam and etodolac for osteoarthritis and rheumatoid arthritis. Reviewed May 2004. London (UK): National Institute for Clinical Excellence; 2001 July. Available at: http://www.nice.org.uk/pdf/coxiifullguidance.pdf. Accessed September 8, 2005. 12. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000;43:1905-1915. 13. American College of Rheumatology. Juvenile Arthritis. Atlanta (GA): American College of Rheumatology; 2003 September. Available at: http://www.rheumatology.org/public/ factsheets/jra.asp. Accessed September 19, 2005. 14. National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS). Questions and answers about juvenile rheumatoid arthritis. Bethesda (MD): National Institutes of Health; 2001 July. Available at: http://www.niams.nih.gov/hi/topics/juvenile_arthritis/ juvarthr.htm. Accessed September 8, 2005. 15. American College of Rheumatology. Overview of the Evaluation and Management of Gout and Hyperuricemia. Atlanta (GA): American College of Rheumatology; 2004 October. Available at: http://www.rheumatology.org/publications/primarycare/number4/ hrh0021498.asp. Accessed September 19, 2005. 16. Ankylosing Spondylitis Information from MedicineNet.com, 2004. Available at: http://www.medicinenet.com/ankylosing_spondylitis/article.htm. Accessed September 19, 2005. 17. Mayo Clinic Menstrual cramps (dysmenorrhea), 2005. Available at: http://www.mayoclinic.com/invoke.cfm?id=DS00506. Accessed September 19, 2005. 18. de Berker D., McGregor JM, and Hughes BR on behalf of the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Guidelines for the management of actinic keratoses. Br J Dermatol. 2007;156:222-230. 19. Berman B, Bienstock L, Kuritzky L, Mayeaux EJ Jr, Tyring SK. Actinic keratoses: sequelae and treatments. Recommendatinos from a consensus panel. J Fam Pract. 2006;55:suppl 1-8. 20. Riff DS, Duckor S, Gottlieb I, et al. Diclofenac potassium liquid-filled soft gelatin capsules in the management of patients with postbunionectomy pain: a Phase III, multicenter, randomized, double-blind, placebo-controlled study conducted over 5 days. Clin Ther. 2009;31:2072-2085. 21. Sprix Prescribing Information. American Regent, Inc. June 2015.

Page 509 22. Indocin Prescribing Information. IROKO Pharmaceuticals, LLC. November 2012. 23. Pennsaid Prescribing Information. Mallinckrodt Brand Pharmaceuticals, Inc. January 2015. 24. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2012 Apr;60(4):616-31. 25. The National Committee for Quality Assurance (NCQA). Use of high-risk medications in the elderly (DAE). Available at www.ncqa.org. Accessed September 10, 2014. 26. Ibuprofen Comfort Pac Prescribing Information. Amneal Pharmaceuticals, August 2013. 27. Tivorbex Prescribing Information. Iroko Pharmaceuticals, February 2014. 28. Cambia Prescribing Information. Depomed, Inc., November 2014.

Page 510 NonFormulary Exception Process

Prior Authorization Guideline

GL-67151 NonFormulary Exception Process

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2020 P&T Approval Date: 3/18/2020

P&T Revision Date:

1 . Criteria

Approval Length 12 month(s) Guideline Type Non Formulary

Approval Criteria

1 - Patient has a failure, contraindication, or intolerance to at least three clinically similar formulary drugs. If only one or two clinically similar formulary drugs are available, the patient must have a failure, contraindication, or intolerance to all available clinically similar formulary drugs.

Page 511 OR

2 - No clinically similar formulary drug is appropriate to treat the patient’s condition.

2 . Background

Benefit/Coverage/Program Information

Background

The purpose of this guideline is to establish policies and procedures on how to handle nonformulary drugs that do not have official criteria posted or available. This guideline will not apply to drugs that are benefit exclusions, drugs with step therapy edits, drugs that require quantity limit review only, or drugs that are not reviewed for prior authorization by OptumRx.

3 . Revision History

Date Notes

5/29/2020 3/2020 P&T - New program

Page 512 Nourianz (istradefylline) - PA/Med Nec

Prior Authorization Guideline

GL-79311 Nourianz (istradefylline) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 3/1/2021 P&T Approval Date: 12/18/2019 P&T Revision Date: 12/16/2020

1 . Indications Drug Name: Nourianz (istradefylline) Parkinson's Disease Indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease experiencing “off” episodes.

2 . Criteria

Product Name: Nourianz [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 513

Approval Criteria

1 - Diagnosis of Parkinson's disease

AND

2 - Used as adjunctive treatment to levodopa/carbidopa in patients experiencing “off” episodes

AND

3 - History of failure, contraindication, or intolerance to TWO anti-Parkinson’s disease therapy from the following adjunctive pharmacotherapy classes (trial must be from two different classes):

• Dopamine agonists (e.g., pramipexole, ropinirole) • Catechol-O-methyl transferase (COMT) inhibitors (e.g., entacapone) • Monoamine oxidase (MAO) B inhibitors (e.g., rasagiline, selegiline)

Product Name: Nourianz [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Nourianz therapy

AND

2 - Patient will continue to receive treatment with a carbidopa/levodopa-containing medication

Page 514 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background: Nourianz (istradefylline) is indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease experiencing “off” episodes Additional Clinical Rules:

4 . References

1. Nourianz [package insert]. Bedminster; NJ: Kyowa Kirin, Inc; August 2019. 2. Lang, T, Tarsy D. Medical management of motor fluctuations and dyskinesia in Parkinson disease. In: UpToDate, Hurtig HI (ed). UpToDate. Waltham, MA. Accessed October 2020.

5 . Revision History

Date Notes

1/6/2021 Annual review. Updated references.

Page 515 Nucynta (tapentadol), Tramadol-containing Products

Prior Authorization Guideline

GL-32590 Nucynta (tapentadol), Tramadol-containing Products

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 6/23/2009; P&T Revision Date: 9/28/2016 **Effective 1/1/2017**

1 . Indications Drug Name: ConZip (tramadol) extended-release capsules; generic tramadol ER capsules (100 mg, 200 mg, 300 mg); brand and generic tramadol ER 150 mg capsules; Ultram ER (tramadol) extended-release tablets; and generic tramadol ER tablets [biphasic, non-biphasic] Moderate to moderately severe chronic pain Indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time

Drug Name: Nucynta (tapentadol) tablets Moderate to severe acute pain Indicated for the management of moderate to severe acute

Page 516 pain in adults

Drug Name: Ultracet (tramadol/acetaminophen) tablets Acute pain Indicated for the short-term (five days or less) management of acute pain

Drug Name: Ultram (tramadol) tablets Moderate to moderately severe pain Indicated for the management of moderate to moderately severe pain in adults

2 . Criteria

Product Name: ConZip or Brand Tramadol ER 100, 150, 200, 300 mg capsules (biphasic) Approval Length 12 Month Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to moderately severe chronic pain

AND

2 - History of failure, contraindication, or intolerance to both of the following:

2.1 Tramadol containing product [e.g., Ultram (tramadol), Ultracet (tramadol/acetaminophen)]

AND

2.2 All of the following opioids: [D]

• Acetaminophen with codeine (e.g., Tylenol #3) • Hydrocodone-containing product [e.g., Vicodin (hydrocodone/acetaminophen), Norco (hydrocodone/acetaminophen)] • Morphine extended-release (e.g., MS Contin) • OxyContin (oxycodone extended-release)

Page 517 Product Name: Brand Ultram ER, Generic tramadol ER tablet, or Generic tramadol ER tablet (biphasic) Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following:

• tramadol • tramadol/acetaminophen

Product Name: Brand Ultracet or Brand Ultram Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - History of failure, contraindication, or intolerance to two of the following formulary immediate-release (IR) opioids: [B]

• Tramadol containing product (e.g., generic tramadol, generic tramadol/acetaminophen) • Acetaminophen with codeine (e.g., Tylenol #3) • Hydrocodone-containing product [e.g., Vicodin (hydrocodone/acetaminophen), Norco (hydrocodone/acetaminophen)]

Product Name: Nucynta Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - History of failure, contraindication, or intolerance to both of the following formulary immediate-release (IR) opioids:

1.1 Tramadol containing product [e.g., Ultram (tramadol), Ultracet (tramadol/acetaminophen)] [C]

Page 518

AND

1.2 One of the following: [A]

• Oxycodone immediate-release (e.g., OxyIR) • Morphine immediate-release (e.g., MSIR) • Dilaudid (hydromorphone immediate-release)

3 . Background

Benefit/Coverage/Program Information

Quantity Limit

These products are subject to a standard quantity limit. The quantity limit may vary from the standard limit based upon plan-specific benefit design. Please refer to your benefit materials.

4 . Endnotes

A. Effective June 22, 2009 Nucynta was placed into schedule II of the Controlled Substances Act (CSA). [12] In clinical trials Nucynta was compared to oxycodone IR and morphine. Nucynta 50 mg and 75 mg was found noninferior to oxycodone 10 mg IR. [13] B. Short-acting, weak opioids, such as Darvon, Darvocet, Tylenol w/codeine, and Vicodin are appropriate alternatives for non-scheduled tramadol products. [15] C. A trial of Ultram prior to Nucynta is recommended. If a patient has to fail only one drug, then it would be a trial of Ultram, not a CII. All patients should be required to have a trial of Ultram before getting Nucynta, including those who have already tried oxycodone or morphine. It would also be preferable and appropriate to require failure to two agents. [19] D. Don't have any good efficacy data for Conzip-don't know why the FDA approved this drug. IR component is highly abused: get a rapid increase in opioid concentration. Conzip criteria should include failure of all available opioids (CII and CIII, as well as tramadol). [15]

5 . References

Page 519 1. Nucynta Prescribing Information. Janssen Pharmaceuticals, Inc., September 2013. 2. Tramadol Extended-Release Tablets Prescribing Information. PAR Pharmaceutical Companies, Inc., September 2014. 3. Ultram ER Prescribing Information. Janssen Pharmaceuticals, Inc., July 2014. 4. Tramadol Extended-Release Capsules (100 mg, 200 mg, 300 mg) Prescribing Information. Trigen Laboratories, LLC., June 2015. 5. Health care guidelines. Acute Pain Assessment and Opioid Prescribing Protocol. Institute for Clinical Systems Improvement (ICSI) Web site. https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/ catalog_pain_guidelines/opioids/. Accessed November 4, 2015. 6. International Association of the Study of Pain. Dworkin RH, O'Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237-251. 7. Chou R, Qaseem A, Snow V et al. Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007;147:478-491. 8. Antman EM, Bennett JS, Daugherty A et al. Use of nonsteroidal antiinflammatory drugs: An Update for clinician: a scientific statement from the American Heart Association. Circulation. 2007; 115:1634-1642. 9. Burkhardt C.S., Goldenberg, D, Crofford L et al. Guidelines for the Management of Fibromyalgia Syndrome Pain in Adults and Children. APS Clinical Practice Guidelines Series, No. 4. Glenview, IL: American Pain Society 2005. 10. Simon LS, Lipman AG, Caudill-Slosberg M. Guidelines for the Management of Pain in Osteoarthritis, Rheumatoid Arthritis, and Juvenile Chronic Arthritis. APS Clinical Practice Guidelines Series, No. 2. Glenview, IL: American Pain Society 2002. 11. American College of Rheumatology (ACR) 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. ACR Web site. http://www.rheumatology.org/Portals/0/Files/ACR%20Recommendations%20for%20the %20Use%20of%20Nonpharmacologic%20and%20Pharmacologic%20Therapies%20in %20OA%20of%20the%20Hand,%20Hip%20and%20Knee.pdf. Accessed November 4, 2015. 12. Department of Justice. Drug Enforcement Administration. Schedules of Controlled Substances: Placement of Tapentadol into Schedule II. DEA Web site. http://www.deadiversion.usdoj.gov/fed_regs/rules/2009/fr05212.htm. Accessed November 4, 2015. 13. Hartrick C, Van Hove I, Stegmann J-U et al. Efficacy and tolerability of tapentadol immediate release and oxycodone HCl immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: a 10 day, phase III, randomized, double-blind, active- and placebo-controlled study. Clin Therap. 2009; April 31(2):260- 271. 14. Hale M, Upmalis D, Okamoto A et al. Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study. Curr Med Research and Opinions 2009; 25(5): 1095- 1104. 15. Per clinical consultation with pain specialist, September 21, 2010. 16. Ultracet Prescribing Information. Janssen Pharmaceuticals, Inc., July 2014. 17. Ultram Prescribing Information. Janssen Pharmaceuticals, Inc., July 2014. 18. Conzip Prescribing Information. Vectical Pharmaceuticals, Inc., June 2011. 19. Per clinical consultation with pain specialist, February 16, 2010.

Page 520 20. Per clinical consultation with pain specialist, November 1, 2011. 21. Tramadol Extended-Release Capsules (150 mg) Prescribing Information. STA3, LLC., May 2015. 22. NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain. v.2.2015. National Comprehensive Cancer Network Web site. Available at: http://www.nccn.org/professionals/physician_gls/pdf/pain.pdf. Accessed November 6, 2015. 23. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758-65. 24. Per clinical consultation with pain specialist, November 6, 2015.

Page 521 Nuedexta (dextromethorphan/quinidine) – PA/Med Nec

Prior Authorization Guideline

GL-71799 Nuedexta (dextromethorphan/quinidine) – PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/15/2020

P&T Revision Date:

1 . Indications Drug Name: Nuedexta (dextromethorphan/quinidine) Pseudobulbar affect (PBA) Indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying.

2 . Criteria

Product Name: Nuedexta [a] Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 522

Approval Criteria

1 - Diagnosis of pseudobulbar affect

AND

2 - One of the following

• Amyotrophic lateral sclerosis (ALS) • Alzheimer's disease • Multiple sclerosis (MS) • Parkinson's disease • Stroke • Traumatic brain injury

AND

3 - Documented absence of cardiac rhythm disorders

AND

4 - Prescribed by or in consultation with a neurologist Notes State mandates may apply. Any federal regulatory requirements and th e member specific benefit plan coverage may also impact coverage crit eria. Other policies and utilization management programs may apply.

Product Name: Nuedexta [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to therapy Notes State mandates may apply. Any federal regulatory requirements and th e member specific benefit plan coverage may also impact coverage crit

Page 523 eria. Other policies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background:

Nuedexta, a combination product containing dextromethorphan hydrobromide and quinidine sulfate, is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or are inappropriate to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury. Additional Clinical Programs: Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Nuedexta [package insert]. Aliso Viejo, CA: Avanir Pharmaceuticals, Inc.; January 2019. 2. Ahmed, A, Simmons, Z. Pseudobulbar affect: prevalence and management. Ther Clin Risk Manag. 2013: 9; 483-89.

5 . Revision History

Date Notes

8/27/2020 New program

Page 524 Nuplazid (pimavanserin tartrate)

Prior Authorization Guideline

GL-77864 Nuplazid (pimavanserin tartrate)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 7/27/2016 P&T Revision Date: 08/16/2019 ; 10/16/2019 ; 11/13/2020

1 . Indications Drug Name: Nuplazid Parkinson's disease psychosis Indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

2 . Criteria

Product Name: Nuplazid Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Page 525

Approval Criteria

1 - Diagnosis of Parkinson's disease

Product Name: Nuplazid Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to Nuplazid therapy.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place. Background Nuplazid (pimavanserin) is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.

4 . References

1. Nuplazid [package insert]. San Diego, CA: Acadia Pharmaceuticals Inc.; September 2019.

5 . Revision History

Page 526

Date Notes

12/4/2020 Annual review. Updated references.

Page 527 Nurtec ODT (rimegepant), Ubrelvy (ubrogepant) - PA/Med Nec

Prior Authorization Guideline

GL-81875 Nurtec ODT (rimegepant), Ubrelvy (ubrogepant) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 9/1/2020 P&T Revision Date: 09/16/2020 ; 2/19/2021

1 . Indications Drug Name: Nurtec ODT (rimegepant) Migraine Indicated for the acute treatment of migraine with or without aura in adults

Drug Name: Ubrelvy (ubrogepant) Migraine Indicated for the acute treatment of migraine with or without aura in adults

2 . Criteria

Product Name: Ubrelvy [a] Diagnosis Migraine Approval Length 12 month(s)

Page 528 Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Used for acute treatment of migraine

AND

2 - Documentation of a one month trial resulting in therapeutic failure, contraindication or intolerance to two of the following:

• almotriptan (Axert) • eletriptan (Relpax) • frovatriptan (Frova) • naratriptan (Amerge) • rizatriptan (Maxalt/Maxalt MLT) • sumatriptan (Imitrex) • zolmitriptan (Zomig)

AND

3 - Prescribed by or in consultation with one of the following specialists with expertise in the acute treatment of migraine:

• Neurologist • Pain Specialist • Headache Specialist [b]

AND

4 - One of the following:

4.1 Patient is currently treated with one of the following prophylactic therapies:

• Amitriptyline (Elavil) • A beta-blocker (i.e., atenolol, metoprolol, nadolol, propranolol, or timolol) • A biologic calcitonin gene-related peptide receptor (CGRP) antagonist for preventive treatment of migraine [i.e., Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Vyepti (eptinezumab-jjmr)] • Divalproex sodium (Depakote/Depakote ER)

Page 529 • OnabotulinumtoxinA (Botox) [c] • Topiramate (Topamax) • Venlafaxine (Effexor/Effexor XR)

4.2 Patient has less than 4 migraine days per month

4.3 Patient has greater than or equal to 4 migraine days per month and has contraindication or intolerance to one of the following prophylactic therapies:

AND

5 - Medication will not be used in combination with another acute calcitonin gene-related peptide receptor (CGRP) antagonists (i.e., Nurtec ODT*) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Headache specialists are physicians certified by the United Coun cil for Neurologic Subspecialties (UCNS). [c] Coverage of onabotulinu mtoxinA (Botox) may be subject to additional benefit and coverage revi ew requirements. *Nurtec ODT is typically excluded from coverage

Product Name: Nurtec ODT* [a] Diagnosis Migraine Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 530 Guideline Type Prior Authorization

Approval Criteria

1 - Used for acute treatment of migraine

AND

2 - Documentation of a one month trial resulting in therapeutic failure, contraindication or intolerance to both of the following:

2.1 Two of the following:

• almotriptan (Axert) • eletriptan (Relpax) • frovatriptan (Frova) • naratriptan (Amerge) • rizatriptan (Maxalt/Maxalt MLT) • sumatriptan (Imitrex) • zolmitriptan (Zomig)

AND

2.2 Ubrelvy

AND

3 - Prescribed by or in consultation with one of the following specialists with expertise in the acute treatment of migraine:

• Neurologist • Pain Specialist • Headache Specialist [b]

AND

4 - One of the following:

4.1 Patient is currently treated with one of the following prophylactic therapies:

Page 531 • Amitriptyline (Elavil) • A beta-blocker (i.e., atenolol, metoprolol, nadolol, propranolol, or timolol) • A biologic calcitonin gene-related peptide receptor (CGRP) antagonist for preventive treatment of migraine [i.e., Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Vyepti (eptinezumab-jjmr)] • Divalproex sodium (Depakote/Depakote ER) • OnabotulinumtoxinA (Botox) [c] • Topiramate (Topamax) • Venlafaxine (Effexor/Effexor XR)

4.2 Patient has less than 4 migraine days per month

4.3 Patient has greater than or equal to 4 migraine days per month and has contraindication or intolerance to one of the following prophylactic therapies:

AND

5 - Medication will not be used in combination with another acute calcitonin gene-related peptide receptor (CGRP) antagonists (i.e., Ubrelvy) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Headache specialists are physicians certified by the United Coun cil for Neurologic Subspecialties (UCNS). *Nurtec ODT is typically excl uded from coverage

Page 532 Product Name: Nurtec ODT*, Ubrelvy [a] Diagnosis Migraine Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to therapy

AND

2 - Medication will not be used in combination with another acute calcitonin gene-related peptide receptor (CGRP) antagonists [i.e., Nurtec ODT for Ubrelvy requests, Ubrelvy for Nurtec ODT requests] Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. *Nurtec ODT is typically excluded from coverage

3 . Background

Benefit/Coverage/Program Information

Background: Nurtec ODT (rimegepant)* and Ubrelvy (ubrogepant) are calcitonin gene-related peptide receptor antagonists indicated for the acute treatment of migraine with or without aura in adults. The American Headache Society recommends the use of NSAIDs (including aspirin), non- opioid analgesics, acetaminophen, or caffeinated analgesic combinations (e.g., aspirin/acetaminophen/caffeine) for mild‐to‐moderate attacks and migraine‐specific agents (i.e.,triptans, dihydroergotamine [DHE]) for moderate or severe attacks and mild‐to‐moderate attacks that respond poorly to NSAIDs or caffeinated combinations. This program requires a member to try two generic triptans prior to receiving coverage for Nurtec ODT* or Ubrelvy. Additional Clinical Programs:

Page 533 *Nurtec ODT is typically excluded from coverage

• Supply limits may apply. • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Nurtec ODT [package insert]. New Haven, CT: Biohaven Pharmaceuticals, Inc.; March 2020. 2. Ubrelvy [package insert]. Madison, NJ: Allergan USA, Inc.; June 2020. 3. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache: The Journal of Head and Face Pain. 2019:59; 1-18.

5 . Revision History

Date Notes

3/5/2021 Removed moderate to severe migraine requirement. Added requireme nt for less than 4 migraines per month. Simplified criteria for greater th an or equal to 4 migraines per month. Added biologic CGRP to prophyl actic therapies. Removed prescriber requirement from reauthorization.

Page 534 Ophthalmic Anti-Allergic Agents

Prior Authorization Guideline

GL-35989 Ophthalmic Anti-Allergic Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 10/4/2005; CPS Revision Date: 8/20/2013

1 . Indications Drug Name: Alocril (nedocromil) ophthalmic solution Allergic Conjunctivitis Indicated for the treatment of itching associated with allergic conjunctivitis. [8]

Drug Name: Alomide (lodoxamine) Allergic Conjunctivitis Indicated in the treatment of the ocular disorders referred to by the terms vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis. [9]

Drug Name: Bepreve (bepotastine) Allergic Conjunctivitis Indicated for the treatment of itching associated with allergic

Page 535 conjunctivitis. [3]

Drug Name: Crolom (cromolyn) ophthalmic solution Allergic Conjunctivitis Indicated for the treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis. [6]

Drug Name: Bromsite (bromfenac) ophthalmic solution Postoperative Inflammation and Prevention of Ocular Pain Indicated for the treatment of postoperative inflammation and prevention of ocular pain in patients undergoing cataract surgery.

Drug Name: Elestat (epinastine) ophthalmic solution Allergic Conjunctivitis Indicated for the prevention of itching associated with allergic conjunctivitis. [4]

Drug Name: Emadine (emedastine) Allergic Conjunctivitis Indicated for the temporary relief of the signs and symptoms of allergic conjunctivitis. [10]

Drug Name: Lastacaft (alcaftadine) ophthalmic solution Allergic Conjunctivitis Indicated for the prevention of itching associated with allergic conjunctivitis. [13]

Drug Name: Optivar (azelastine) Allergic Conjunctivitis Indicated for the treatment of itching of the eye associated with allergic conjunctivitis. [5]

Drug Name: Pataday (olopatadine) Allergic Conjunctivitis Indicated for the treatment of ocular itching associated with allergic conjunctivitis. [2]

Drug Name: Patanol (olopatadine) Allergic Conjunctivitis Indicated for the treatment of the signs and symptoms of allergic conjunctivitis. [1]

2 . Criteria

Page 536 Product Name: Bepreve Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following:

• Epinastine • Azelastine

Product Name: Bromsite Approval Length 12 Month Guideline Type Step Therapy

Approval Criteria

1 - History of failure or intolerance to at least one of the following generic single ingredient ophthalmic NSAID solutions:

• diclofenac • flurbiprofen • ketorolac

Product Name: Emadine, Lastacaft, Pataday, or Patanol Guideline Type Non Formulary

Approval Criteria

1 - History of failure, contraindication, or intolerance to both of the following:

• Generic epinastine • Generic azelastine

Product Name: Alocril, Alomide Guideline Type Non Formulary

Page 537

Approval Criteria

1 - History of failure, contraindication, or intolerance to generic cromolyn

3 . Definitions

Definition Description

Allergic Conjunctivitis The types of allergic conjunctivitis include atopic keratoconjunctivitis, [12] simple allergic conjunctivitis, seasonal or perennial conjunctivitis, vernal conjunctivitis, and giant papillary conjunctivitis.

4 . References

1. Patanol Prescribing Information. Alcon., November 2007. 2. Pataday Prescribing Information. Alcon., July 2011. 3. Bepreve Prescribing Information. ISTA Pharmaceuticals, May 2012. 4. Elestat Prescribing Information. Allergan, Inc., December 2011. 5. Optivar Prescribing Information. Meda Pharmaceuticals Inc., July 2010. 6. Crolom Prescribing Information. Bausch&Lomb Incorporated, March 2011. 7. Alamast Prescribing Information. Vistakon, March 2010. 8. Alocril Prescribing Information. Allergan, December 2012. 9. Alomide 1% Prescribing Information. Alcon, July 2011. 10. Emadine Prescribing Information. Alcon, July 2011. 11. American Academy of Ophthalmology. Preferred Practice Pattern-Limited Revision: Conjunctivitis 2011 . Available at http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=79f4327d-6b7d-42e7- bbf3-585e7c3852c7. Accessed July 10, 2013. 12. American Optometric Association. Optometric Clinical Practice Guideline: Care of the patient with conjunctivitis. 2nd ed. St. Louis (MO): American Optometric Association; 2002 Nov 8. Available at: http://www.aoa.org/documents/optometrists/CPG-11.pdf. Accessed July 10, 2013. 13. Lastacaft Prescribing Information. Allergan, Inc., September 2011. 14. Bromsite Prescribing Information. Sun Pharmaceutical Industries, Inc. April 2016.

Page 538 Ophthalmic Corticosteroids (Alrex, Lotemax, Vexol)

Prior Authorization Guideline

GL-5934 Ophthalmic Corticosteroids (Alrex, Lotemax, Vexol)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 7/21/2005; CPS Revision Date: 4/10/2012

1 . Indications Drug Name: Alrex (loteprednol etabonate ophthalmic suspension 0.2%) Allergic conjunctivitis [1-3, 16] Is indicated for the temporary relief of signs and symptoms of seasonal allergic conjunctivitis.

Drug Name: Lotemax suspension/drops (loteprednol etabonate ophthalmic suspension 0.5%) [1-3, 16] Steroid-responsive inflammatory conditions such as allergic conjunctivitis Is indicated for the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctuate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitides, when the inherent hazard of steroid use is accepted to obtain an advisable

Page 539 diminution in edema and inflammation. Is less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis, where 72% of patients treated with Lotemax experienced resolution of anterior chamber cells, compared to 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in IOP (≥10 mmHg) was 1% with Lotemax and 6% with prednisolone acetate 1%. Lotemax should not be used in patients who require a more potent corticosteroid for this indication.

Post-operative inflammation Lotemax is also indicated for the treatment of post-operative inflammation following ocular surgery.

Drug Name: Lotemax ointment (loteprednol etabonate ophthalmic ointment 0.5%) Post-operative inflammation [1-3, 16] Is a corticosteroid indicated for the treatment of postoperative inflammation and pain following ocular surgery.

Drug Name: Vexol (rimexolone ophthalmic suspension 1%) [1-3, 16] Post-operative inflammation Is indicated for the treatment of post-operative inflammation after ocular surgery.

Anterior uveitis Is indicated for the treatment of anterior uveitis.

2 . Criteria

Product Name: Alrex or Lotemax suspension Diagnosis Allergic Conjunctivitis Guideline Type Non Formulary

Approval Criteria

1 - Diagnosis of allergic conjunctivitis

AND

2 - History of failure, contraindication, or intolerance to both of the following: [4]

• azelastine (Optivar) • cromolyn (Crolom )

Page 540 Product Name: Vexol or Lotemax Diagnosis Post-Operative Inflammation Approval Length 1 Time Guideline Type Non Formulary

Approval Criteria

1 - Diagnosis of post-operative ocular inflammation

AND

2 - Prescribed by an ophthalmologist

AND

3 - One of the following:

3.1 Patients who are intolerant of increase in intraocular pressure (IOP) [5, 6, 7, A, B] (ie, patients with glaucoma)

3.2 History of failure, contraindication, or intolerance to three of the following:

• prednisolone acetate (eg, Pred Forte) • prednisolone sodium phosphate (eg, Pred-Phosphate) • fluorometholone (eg, FML , FML Forte, FML Liquifilm) • dexamethasone (eg, Decadron-phosphate) • ketorolac (eg, Acular, Acular LS) • flurbiprofen (Ocufen)

Product Name: Vexol Diagnosis Anterior Uveitis Guideline Type Non Formulary

Page 541 Approval Criteria

1 - Diagnosis of anterior uveitis

AND

2 - Prescribed by an ophthalmologist

AND

3 - One of the following:

3.1 Patients who are intolerant of increase in intraocular pressure (IOP) (ie, patients with glaucoma) [5, 6, 7, B]

3.2 History of failure, contraindication, or intolerance to three of the following:

• prednisolone acetate (eg, Pred Forte) • prednisolone sodium phosphate (eg, Pred-Phosphate) • fluorometholone (eg, FML , FML Forte, FML Liquifilm) • dexamethasone (eg, Decadron-phosphate)

Product Name: Lotemax suspension Diagnosis Other Steroid Responsive Conditions [C] Guideline Type Non Formulary

Approval Criteria

1 - Prescribed by an ophthalmologist

AND

2 - One of the following:

Page 542 2.1 Patients who are intolerant of increase in intraocular pressure (IOP) [5, 6, 7, A] (ie, patients with glaucoma)

2.2 History of failure, contraindication, or intolerance to two of the following:

• prednisolone acetate (eg, Pred Forte) • prednisolone sodium phosphate (eg, Pred-Phosphate) • fluorometholone (eg, FML , FML Forte, FML Liquifilm) • dexamethasone (eg, Decadron-phosphate)

3 . Definitions

Definition Description

Allergic Conjunctivitis The types of allergic conjunctivitis include atopic keratoconjunctivitis, [7] simple allergic conjunctivitis, seasonal or perennial conjunctivitis, vernal conjunctivitis, and giant papillary conjunctivitis.

IOP Intraocular pressure

Uveitis [6] Is characterized by inflammation affecting the iris (iritis), ciliary body (cyclitis), and choroid (choroiditis). The inflammation may occur acutely or recurrently or may chronically manifest itself over months or even years. Although uveitis may affect anterior or posterior ocular structures, or both, anterior uveitis is approximately four times as common as posterior uveitis and occurs most frequently between the ages of 20 and 50 years.

4 . Endnotes

A. In Novack et al. [5], a meta-analysis of all subjects (healthy volunteers, patients with inflammation, or allergy) in all sponsored loteprednol etabonate studies up to the time of the analysis, loteprednol etabonate appeared to have less propensity to cause clinically significant elevations in IOP (greater than or equal to 10 mmHg) than prednisolone acetate. B. Leibowitz et al. [14] conducted a double-masked, randomized, single-eye, crossover protocol study on glucocorticoid topical agents in asymptomatic patients. The results

Page 543 showed that rimexolone has IOP-elevating potential that is significantly lower than dexamethasone sodium phosphate and prednisolone acetate. C. Lotemax suspension/drops is indicated for the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctuate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitides, when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation.

5 . References

1. Alrex Prescribing Information. Bausch & Lomb, April 2011. 2. Lotemax suspension/drops Prescribing Information. Bausch & Lomb, April 2011. 3. Vexol Prescribing Information. Alcon Laboratories, Inc., July 2011. 4. American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Volume 3. Available at: http://www.aaaai.org/ar/working_vol3/i.asp. Accessed on September 8, 2005. 5. Novack GD, Howes J, Crockett RS, Sherwood MB. Change in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma 1998;7(4):266-9. 6. Foster CS, Alter G, DeBarg LR, Raizman MB, Crabb JL, Santos CI, Feiler LS, Friedlaender MH. Efficacy and safety of rimexolone 1% ophthalmic suspension vs. 1% prednisolone acetate in the treatment of uveitis. Am J of Ophthalmol 1996; 122:171-82. 7. American Optometric Association. Optometric Clinical Practice Guideline: Care of the patient with conjunctivitis. 2nd ed. St. Louis (MO): American Optometric Association; 2002 Nov 8. Available at: http://www.aoanet.org/documents/CPG-11.pdf. Accessed on September 30, 2010. 8. American Optometric Association. Clinical Practice Guideline: Care of the patient with anterior uveitis. St. Louis (MO): American Optometric Association; 1999 March. Available at: http://www.aoanet.org/documents/CPG-7.pdf. Accessed on September 30, 2010. 9. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically. Accessed September 30, 2010. 10. Dell SJ, Lowry GM, Northcutt JA, et al. A randomized, double-masked, placebo- controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol 1998;102:251-5. 11. Stewart R, Horwitz B, Howes J, Novack GD, Hart K. Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. J Cataract Refract Surg 1998;24:1480-9. 12. American Optometric Association. Clinical Practice Guideline: Care of the adult patient with cataract. St. Louis (MO): American Optometric Association; 1999 March. Available at: http://www.aoanet.org/documents/CPG-8.pdf. Accessed on September 7, 2005. 13. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern® Guidelines. Conjunctivitis. San Francisco, CA: American Academy of Ophthalmology; 2008. Available at: http://www.aao.org/ppp. Accessed September 30, 2010. 14. Leibowitz HM, Bartlett JD, Rich R, et al. Intraocular pressure-raising potential of 1.0% rimexolone in patients responding to corticosteroids. Arch Ophthalmol. 1996;114: 933- 937.

Page 544 15. Gold Standard, Inc. Drugs indicated for postoperative ocular inflammation. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: September 30, 2010. 16. Lotemax ointment Prescribing Information. Bausch & Lomb, April 2011.

Page 545 Opioid Dependence

Prior Authorization Guideline

GL-78567 Opioid Dependence

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 4/18/2018 P&T Revision Date: 07/17/2019 ; 06/19/2019 ; 06/17/2020 ; 07/15/2020 ; 11/13/2020

1 . Criteria

Product Name: Bunavail Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - The patient is being treated for opioid dependence

AND

Page 546

2 - History of failure, contraindication, or intolerance to BOTH of the following:

• Zubsolv • buprenorphine/naloxone (generic tablet or film)

2 . Background

Benefit/Coverage/Program Information

Background:

Bunavail is a Schedule III narcotic medication available under the Drug Abuse Treatment Act (DATA) of 2000 for the treatment of opioid dependence. Only qualified prescribers with the necessary DEA (Drug Enforcement Agency) identification number can prescribe or dispense buprenorphine products for opioid addiction therapy.

Bunavail contains buprenorphine, a schedule III narcotic and naloxone, an opiate antagonist. Buprenorphine, like other opioids has the potential for being abused. Naloxine is used to guard against misuse by blocking the effects of opiates if the drug is manipulated for injection.

Additional Clinical Rules:

• Supply limits may be in place. • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

3 . References

1. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004. 2. Bunavail [package insert]. Raleigh, NC: BioDelivery Sciences International, Inc.; October 2019.

Page 547

4 . Revision History

Date Notes

12/18/2020 Removed criteria for DATA2000 prescriber. Removed pain manageme nt confirmation.

Page 548 Opioid-containing cough medicines (including: Flowtuss, Hycofenix, Obredon, Tuzistra XR, Tussionex, Tussicaps, Tuxarin ER, Zutripo, codeine/phenylephrine/promethazine, codeine/promethazine, hydrocodone/homatropine, hydrocodone bitartrate/guaifenesin) - PA/Med Nec

Prior Authorization Guideline

GL-73040 Opioid-containing cough medicines (including: Flowtuss, Hycofenix, Obredon, Tuzistra XR, Tussionex, Tussicaps, Tuxarin ER, Zutripo, codeine/phenylephrine/promethazine, codeine/promethazine, hydrocodone/homatropine, hydrocodone bitartrate/guaifenesin) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 3/21/2018 P&T Revision Date: 08/16/2019 ; 08/16/2019 ; 8/14/2020

1 . Criteria

Product Name: Opioid containing cough and cold products Approval Length 1 month(s) Guideline Type Prior Authorization

Page 549 Approval Criteria

1 - Prescriber attests they are aware of FDA labeled contraindications regarding use of opioid containing cough and cold products in patients less than 18 years of age and feels the treatment with the requested product is medically necessary (Document rationale for use).

AND

2 - Patient does not have a comorbid condition that may impact respiratory depression (e.g., asthma or other chronic lung disease, sleep apnea, body mass index > 30)

AND

3 - Patient has tried and failed at least one non-opioid containing cough and cold remedy

2 . Background

Benefit/Coverage/Program Information

Background

Opioid (codeine or hydrocodone) containing cough and cold products are FDA labeled for use in adults 18 years of age and older. Use of prescription opioid cough and cold medicines containing codeine or hydrocodone should be limited in children younger than 18 years old due to serious risks associated with use. Coverage for patients age 18 or greater will process automatically.

3 . References

1. FlowTuss [package insert]. San Antonio, Tx: Mission Pharmacal Company.;October 2018. 2. Zutripro [package insert]. Morristown, NJ: Hawthorn Pharmaceuticals, Inc ; June 2018. 3. Hycofenix [package insert].. San Antonio, Tx: Mission Pharmacal Company; June 2018. 4. Tuzistra XR [package insert]. Englewood, CO: Aytu BioScience, Inc; October 2018.

Page 550 5. Tussionex Pennkinetic ER [package insert]. Smyrna, GA; UCB, Inc; June 2018. 6. Tuxarin ER [package insert]. Louisville, KY: Mainpointe Pharmaceuticals; August 2018. 7. TussiCaps [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals; March 2018. 8. Approach to Cough in Children. UpToDate. February 2018. FDA Round Table. Use of Cough Suppressants in Children; Expert Roundtable Meeting; April 27, 2017. 9. FDA Drug Safety Communication (2018a). FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. US Food and Drug Administration website. https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm. Published January 22, 2018. Accessed July 6, 2020.

4 . Revision History

Date Notes

9/10/2020 Annual review. Updated references.

Page 551 Oriahnn (elagolix and estradiol/norethindrone) - PA/Med Nec

Prior Authorization Guideline

GL-75234 Oriahnn (elagolix and estradiol/norethindrone) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 9/16/2020

P&T Revision Date:

1 . Indications Drug Name: Oriahnn Uterine leiomyomas (fibroids) Indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.

2 . Criteria

Product Name: Oriahnn [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 552

Approval Criteria

1 - Diagnosis of uterine fibroids (leiomyomas)

AND

2 - Used for the management of heavy menstrual bleeding

AND

3 - Patient is premenopausal

AND

4 - History of trial and failure [b], contraindication, or intolerance after a three-month trial to one of the following:

• Estrogen/progestin contraceptive (e.g., Loestrin FE) • Progestin-releasing intrauterine devices (IUDs) (e.g., Mirena) • Progestin-only contraceptive [e.g., norethindrone (generic Micronor)]

AND

5 - History of trial and failure [b], contraindication, or intolerance after a three-month trial of tranexamic acid (e.g., Lysteda)

AND

6 - Prescribed by or in consultation with one of the following:

• Obstetrics/Gynecologist (OB/GYN) • Reproductive endocrinologist

Page 553 y. [b] For Connecticut and Kentucky business, only a 30 day trial will be required.

Product Name: Oriahnn [a] Approval Length 6 months up to a maximum of 24 months Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to therapy

AND

2 - Impact to bone mineral density has been considered

AND

3 - Treatment duration has not exceeded a total of 24 months Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. NOTE: Oriahnn is indicated for a maximum of 24 months

3 . Background

Benefit/Coverage/Program Information

Background Oriahnn is a gonadotropin-releasing hormone (GnRH) receptor antagonist, elagolix, co- packaged with estradiol/norethindrone indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and re-

Page 554 authorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place.

4 . References

1. Oriahnn [package insert]. North Chicago, IL: AbbVie Inc.; May 2020 2. Sabry, M, Al-Hendy, Ayman. Medical Treatment of Uterine Leiomyoma. Reprod Sci. 2012:19(4):339-53.

5 . Revision History

Date Notes

10/13/2020 New program

Page 555 Osphena (ospemifene)

Prior Authorization Guideline

GL-84799 Osphena (ospemifene)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 3/20/2019 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Indications Drug Name: Osphena (ospemifene) Moderate to severe dyspareunia Indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause and for the treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy (VVA) due to menopause.

2 . Criteria

Product Name: Osphena Diagnosis Benefit designs covering medications to treat sexual dysfunction Approval Length 12 month(s)

Page 556 Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - Diagnosis of one of the following:

• Treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause • Treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy (VVA) due to menopause

Product Name: Osphena Diagnosis Benefit designs excluding medications to treat sexual dysfunction Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - Treatment of moderate to severe vaginal dryness, a symptom of VVA due to menopause

Product Name: Osphena Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to therapy

3 . Background

Page 557 Benefit/Coverage/Program Information

Additional Clinical Rules:

• Supply limits may be in place • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. Background:

Osphena (ospemifene) is indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause and for the treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy (VVA) due to menopause.

4 . References

1. Osphena [package insert]. Florham Park, NJ: Shionogi Inc.; January 2019.

5 . Revision History

Date Notes

4/5/2021 Annual review. No changes.

Page 558 Overactive Bladder Agents

Prior Authorization Guideline

GL-31907 Overactive Bladder Agents

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 12/6/2004; P&T Revision Date: 8/18/2016. **Effective 1/1/2017**

1 . Indications Drug Name: Detrol LA (tolterodine extended-release), Myrbetriq (mirabegron) Overactive Bladder Indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

2 . Criteria

Product Name: Brand Detrol LA or Myrbetriq

Page 559 Guideline Type Step Therapy

Approval Criteria

1 - History of both of the following:

• oxybutynin IR/ER • VESIcare

3 . References

1. Detrol LA Prescribing Information. Pfizer, September 2013. 2. Mybetriq Prescribing Information. Astellas Pharma US, Inc., August 2016.

Page 560 Oxistat (oxiconazole) cream - PA/Med Nec

Prior Authorization Guideline

GL-76615 Oxistat (oxiconazole) cream - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2021 P&T Approval Date: 8/20/2014 P&T Revision Date: 09/18/2019 ; 10/21/2020

1 . Indications Drug Name: Oxistat Tinea dermal infections including tinea versicolor (i.e., pityriasis versicolor) Indicated for patients with tinea dermal infections including tinea versicolor (i.e., pityriasis versicolor) a common superficial fungal infection. Tinea versicolor often presents as hypopigmented, hyperpigmented, or erythematous macules on the trunk and proximal upper extremities. The causative organisms are yeasts in the genus Malassezia (formerly known as Pityrosporum).

2 . Criteria

Product Name: Oxistat Cream [a] Diagnosis Tinea dermal infections including tinea versicolor (i.e., pityriasis versicolor)

Page 561 Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of tinea versicolor

AND

2 - History of failure, contraindication, or intolerance to one of the following topical antifungal agents:

• Ketoconazole 2% cream (generic Nizoral) • Ciclopirox 0.77% cream (generic Loprox)

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

• Supply limits and/or Step Therapy may be in place • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. Background:

Oxistat (oxiconazole) cream is indicated for patients with tinea dermal infections including tinea versicolor (i.e., pityriasis versicolor) a common superficial fungal infection. Tinea versicolor often presents as hypopigmented, hyperpigmented, or erythematous macules on the trunk and proximal upper extremities. The causative organisms are yeasts in the genus Malassezia (formerly known as Pityrosporum). Most tinea dermal infections are treatable with over-the- counter medications. Coverage of Oxistat cream will only be provided for tinea versicolor infections after meeting these requirements.

Page 562 4 . References

1. Oxistat [package insert]. Melville, NY: E. Fougera & CO; February 2019. 2. Ketoconazole [package insert]. Melville, NY: E. Fougera & CO; August 2020. 3. Loprox [package insert]. Fairfield, NJ: Medimetriks Pharmaceuticals, Inc; November 2018.

5 . Revision History

Date Notes

11/4/2020 Annual review. Updated references.

Page 563 Pancreatic Enzyme Products (PEPs) - Step Therapy

Prior Authorization Guideline

GL-72495 Pancreatic Enzyme Products (PEPs) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/8/2014 P&T Revision Date: 07/17/2019 ; 7/15/2020

1 . Criteria

Product Name: Pancreaze, Pertzye or Viokace [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to both of the following medications:

• Creon • Zenpep

Page 564 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

2 . Background

Benefit/Coverage/Program Information

Background:

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try Creon and Zenpep before providing coverage for Pancreaze, Pertzye or Viokace.

Members, who have received at least a 90 day supply of Pancreaze, Pertzye or Viokace in the past 120 days as documented in claims history, will be allowed continued coverage of their current therapy.

Additional Clinical Rules:

3 . References

1. Creon [package insert]. North Chicago IL: AbbVie Inc.; March 2020. 2. Pancreaze [package insert]. Campbell, CA: Vivus, Inc; October 2018. 3. Pertzye [package insert]. Bethlehem, PA: Digestive Care, Inc.; March 2020. 4. Viokace [package insert]. Irvine, CA: Allergan, USA; March 2020. 5. Zenpep [package insert]. Irvine, CA: Allergan, USA; March 2020.

4 . Revision History

Page 565 Date Notes

8/27/2020 Annual review. Updated references.

Page 566 Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel- PA/Med Nec

Prior Authorization Guideline

GL-88657 Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel- PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 10/21/2020 P&T Revision Date: 03/17/2021 ; 5/21/2021

1 . Indications Drug Name: Phexxi Prevention of Pregnancy Indicated for the prevention of pregnancy in females of reproductive potential for use as an on-demand method of contraception.

2 . Criteria

Product Name: Phexxi [a] Approval Length 12 month(s) Guideline Type Prior Authorization

Page 567

Approval Criteria

1 - Used for the prevention of pregnancy

AND

2 - Patient is unable to use all of following other methods of contraception due to failure, contraindication, intolerance or refusal (document reason for each method):

• Injection (e.g., Depo-Provera) • Oral Contraceptive [e.g., norethindrone (generic Micronor), Yaz] • Transdermal Patch (e.g. Twirla, Xulane) • Vaginal Contraceptive Ring (e.g., Annovera, NuvaRing) • Diaphragm • Sponge (e.g. Today) • Cervical Cap (e.g., FemCap) • Female Condom

AND

3 - History of failure, contraindication, or intolerance to nonoxynol-9 based spermicide

AND

4 - Provider attests they have counseled the patient regarding a higher rate of pregnancy prevention with the use of other methods of contraception (e.g., injection, oral contraception, transdermal patch, vaginal ring) compared to Phexxi Notes a State mandates may apply. Any federal regulatory requirements and the member specific benefit plan coverage may also impact coverage c riteria. Other policies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Page 568 Background: Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel is indicated for the prevention of pregnancy in females of reproductive potential for use as an on-demand method of contraception. Phexxi is not effective for the prevention of pregnancy when administered after intercourse. Additional Clinical Programs:

4 . References

1. Phexxi [package insert]. San Diego, CA: Evofem, Inc; July 2020.

5 . Revision History

Date Notes

6/21/2021 Modified provider attestation statement.

Page 569 Praluent (alirocumab) - PA/Med Nec

Prior Authorization Guideline

GL-89588 Praluent (alirocumab) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 5/20/2015 P&T Revision Date: 12/19/2018 ; 12/18/2019 ; 02/14/2020 ; 02/19/2021 ; 6/16/2021

1 . Indications Drug Name: Praluent (alirocumab) Primary hyperlipidemia Indicated as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C).[1]

Cardiovascular Disease Indicated to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.

Homozygous Familial Hypercholesterolemia Indicated as an adjunct to other lipid-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C. [1]

2 . Criteria

Page 570

Product Name: Praluent* [a] Diagnosis Hyperlipidemia Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

1.1 Heterozygous familial hypercholesterolemia (HeFH) as confirmed by one of the following**¥:

1.1.1 Both of the following:[14-16]

1.1.1.1 Pre-treatment LDL-C greater than 190 mg/dL (greater than 155 mg/dL if less than 16 years of age)

AND

1.1.1.2 One of the following:

• Family history of myocardial infarction in first-degree relative less than 60 years of age • Family history of myocardial infarction in second-degree relative less than 50 years of age • Family history of LDL-C greater than 190 mg/dL in first- or second-degree relative • Family history of heterozygous or homozygous familial hypercholesterolemia in first- or second-degree relative • Family history of tendinous xanthomata and/or arcus cornealis in first- or second-degree relative

1.1.2 Both of the following:[14-16]

1.1.2.1 Pre-treatment LDL-C greater than 190 mg/dL (greater than 155 mg/dL if less than 16 years of age)

AND

Page 571

1.1.2.2 One of the following:

• Functional mutation in LDL, apoB, or PCSK9 gene* • Tendinous xanthomata • Arcus cornealis before age 45

1.2 Atherosclerotic cardiovascular disease (ASCVD) as confirmed by one of the following:

• Acute coronary syndromes • History of myocardial infarction • Stable or unstable angina • Coronary or other arterial revascularization • Stroke • Transient ischemic attack • Peripheral arterial disease presumed to be of atherosclerotic origin

AND

2 - One of the following:

2.2 Both of the following:

2.2.1 Patient is unable to tolerate high-intensity statin as evidenced by one of the following intolerable and persistent (i.e. more than 2 weeks) symptoms:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations less than 10 times upper limit of normal [ULN])

AND

2.2.2 One of the following:

Page 572

2.2.2.1 Patient has been receiving at least 12 consecutive weeks of moderate-intensity [i.e. atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin greater than or equal to 20 mg, pravastatin greater than or equal to 40 mg, lovastatin 40 mg, Lescol XL (fluvastatin XL) 80 mg, fluvastatin 40 mg twice daily or Livalo (pitavastatin) greater than or equal to 2 mg] and will continue to receive a moderate-intensity statin at maximally tolerated dose

2.2.2.2 Patient has been receiving at least 12 consecutive weeks of low-intensity [i.e. simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg, fluvastatin 20-40 mg, or Livalo (pitavastatin) 1 mg] statin therapy and will continue to receive a low-intensity statin at maximally tolerated dose

2.3 Patient is unable to tolerate low or moderate-, and high-intensity statins as evidenced by one of the following:

2.3.1 One of the following intolerable and persistent (i.e. more than 2 weeks) symptoms for low or moderate-, and high-intensity statins:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations less than 10 times upper limit of normal [ULN])

2.3.2 Patient has a labeled contraindication to all statins

2.3.3 Patient has experienced rhabdomyolysis or muscle symptoms with statin treatment with CK elevations greater than 10 times ULN

AND

3 - One of the following:

Page 573 3.1 One of the following LDL-C values while on maximally tolerated lipid lowering therapy for a minimum of at least 12 weeks within the last 120 days:

• LDL-C greater than or equal to 100 mg/dL with ASCVD • LDL-C greater than or equal to 130 mg/dL without ASCVD

3.2 Both of the following:

3.2.1 One of the following LDL-C values while on maximally tolerated lipid lowering therapy for a minimum of at least 12 weeks within the last 120 days:

• LDL-C between 70 mg/dL and 99 mg/dL with ASCVD • LDL-C between 100 mg/dL and 129 mg/dL without ASCVD

AND

3.2.2 One of the following:

• Patient has been receiving at least 12 consecutive weeks of ezetimibe (Zetia) therapy as adjunct to maximally tolerated statin therapy • Patient has a history of contraindication, or intolerance to ezetimibe

AND

4 - History of failure, contraindication, or intolerance to Repatha (evolocumab) (document date of trial and list reason for therapeutic failure, contraindication, or intolerance)

AND

5 - Used as an adjunct to a low-fat diet and exercise

AND

6 - Not used in combination with another proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor [e.g., Repatha (evolocumab)]

Page 574 AND

7 - Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided Notes *Praluent is excluded from coverage for the majority of our benefits **R esults of prior genetic testing can be submitted as confirmation of diagn osis of HeFH, however please note that UnitedHealthcare does not cur rently cover genetic testing for evidence of an LDL-receptor mutation, f amilial defective apo B-100 or a PCSK9 mutation. ¥ No coverage of Pr aluent will be provided for the primary prevention of cardiovascular eve nts and/or for the lowering of low-density lipoprotein cholesterol in patie nts with primary hyperlipidemia who do not have heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular dis ease (ASCVD) as the use of PCSK9 inhibitors in this population is not supported by the 2018 American College of Cardiology/ American Hear t Association Cholesterol Clinical Practice Guidelines. [a] State mandat es may apply. Any federal regulatory requirements and the member sp ecific benefit plan coverage may also impact coverage criteria. Other p olicies and utilization management programs may apply.

Product Name: Praluent* [a] Diagnosis Homozygous Familial Hypercholesterolemia Approval Length 12 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of homozygous familial hypercholesterolemia (HoFH) as confirmed by both of the following:**

1.1 One of the following:

• Pre-Treatment LDL-C greater than 500 mg/dL • Treated LDL-C greater than 300 mg/dL

AND

1.2 One of the following:

• Xanthoma before 10 years of age

Page 575 • Evidence of heterozygous familial hypercholesterolemia (HeFH) in both parents

AND

2 - Used as an adjunct to a low-fat diet and exercise

AND

3 - Patient is receiving other lipid-lowering therapy (e.g., statin, ezetimibe, LDL apheresis)

AND

4 - Not used in combination with another proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor [e.g., Repatha (evolocumab)]

AND

5 - Not used in combination with Juxtapid (lomitapide)

AND

6 - History of failure, contraindication, or intolerance to Repatha (evolocumab) (document date of trial and list reason for therapeutic failure, contraindication, or intolerance)

AND

Page 576 es and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background: Praluent® (alirocumab) is a PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor antibody indicated:

• To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. • As adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C). ¥ • As an adjunct to other lipid-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.1 Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class • Supply limits may be in place • Step therapy may be in place

4 . References

1. Praluent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals; April 2021. 2. WHO Familial Hypercholesterolemia Consultation Group. Familial Hypercholesterolemia (FH): report of a second WHO consultation. Geneva: World Health Organization; 1999. 3. Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ. 1991;303:893-6. 4. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-934. 5. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015a; DOI: 10.1056/NEJMoa1410489 [Epub ahead of print]. 6. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251:365-74.

Page 577 7. ATP III Final Report PDF. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421. 8. Per clinical drug consult with cardiologist. August 3, 2015 9. Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370:1809-19. 10. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223:262-8. 11. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double- blind, placebo-controlled trial. Lancet. 2015;385:341-50. 12. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercohlesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35:2146-57. 13. Lloyd-Jones D, Morris P, Ballantyne C, et al. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholersterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2016;68:92-125. 14. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. American journal of epidemiology. 2004;160:407-420. 15. Haase A, Goldberg AC. Identification of people with heterozygous familial hypercholesterolemia. Current opinion in lipidology. 2012;23:282-289. 16. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. European heart journal. 2013;34:3478-3490a. 17. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017; Suppl 2;23:1-87. 18. Lloyd-Jones D, Morris P, Ballantyne C, et al. 2017 Focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL- cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2017. 19. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; DOI: 10.1161/CIR.0000000000000625.

5 . Revision History

Date Notes

7/8/2021 Added Praluent exclusion statement. Added history of failure, contrain

Page 578 dication, or intolerance to Repatha to all criteria. Removed prescriber s pecialist requirement. Removed submission of medical records require ment throughout criteria. Changed initial authorization duration to 12 m onths to align all PCSK9 programs. Removed reauthorization criteria. Added HoFH criteria per new indication. Updated references.

Page 579 Premenstrual Dysphoric Disorder Agents (Sarafem, Selfemra)

Prior Authorization Guideline

GL-5991 Premenstrual Dysphoric Disorder Agents (Sarafem, Selfemra)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 9/8/2000; CPS Revision Date: 8/16/2011

1 . Indications Drug Name: Sarafem (fluoxetine) and Selfemra (fluoxetine) Premenstrual Dysphoric Disorder (PMDD) [1, 2] Are indicated for the treatment of premenstrual dysphoric disorder (PMDD). The efficacy of fluoxetine in the treatment of PMDD was established in 3 placebo-controlled trials. The essential features of PMDD, according to the DSM-IV, include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating, and weight gain. These symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school or with usual social activities and relationships with others. In making the diagnosis, care should be taken to rule out other cyclical mood disorders that may be exacerbated by treatment

Page 580 with an antidepressant. The effectiveness of fluoxetine in long-term use, that is, for more than 6 months, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use fluoxetine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

2 . Criteria

Product Name: Sarafem or Selfemra Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of premenstrual dysphoric disorder (PMDD)

AND

2 - History of failure, contraindication, or intolerance to two of the following:

• Paxil CR (paroxetine controlled-release) • Prozac (fluoxetine) • Zoloft (sertraline)

3 . References

1. Sarafem Prescribing Information. Eli Lilly and Company, June 2009. 2. Selfemra Prescribing Information. Teva Phrmaceuticals, March 2009.

Page 581 Prevpac (lansoprazole, amoxicillin and clarithromycin)

Prior Authorization Guideline

GL-40869 Prevpac (lansoprazole, amoxicillin and clarithromycin)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 6/16/2006; P&T Revision Date: 5/21/2014, 12/20/2017; **Effective Date: 02/01/2018**

1 . Indications Drug Name: Prevpac (lansoprazole, amoxicillin, and clarithromycin) Eradication of H. pylori infection to reduce the risk of duodenal ulcer recurrence The components in Prevpac (lansoprazole, amoxicillin, and clarithromycin) are indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Prevpac and other antibacterial drugs, Prevpac should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of

Page 582 therapy.

2 . Criteria

Product Name: Brand Prevpac Approval Length 12 Months Guideline Type Step Therapy

Approval Criteria

1 - History of one of the following:

• Omeclamox-Pak • Pylera

Notes NOTE TO PRESCRIBER: In patients with persistent H.pylori infection, every effort should be made to avoid antibiotics that have been previou sly taken by the patient. [4]

3 . Endnotes

A. In the United States, the recommended primary therapies for H. pylori infection include: a PPI, clarithromycin, and amoxicillin, or metronidazole (clarithromycin-based triple therapy) for 14 days or a PPI or H2RA, bismuth, metronidazole, and tetracycline (bismuth quadruple therapy) for 10–14 days. [4] B. The most important predictors of treatment failure following anti-H. pylori therapy include poor compliance and antibiotic resistance. It is critical for clinicians to stress the importance of taking the medications as prescribed to minimize the likelihood of treatment failure and development of antibiotic resistance. [4]

4 . References

1. Helidac Prescribing Information. Prometheus Laboratories, Inc., June 2012. 2. Prevpac Prescribing Information. Takeda Pharmaceuticals America, Inc., October 2013. 3. Pylera Prescribing Information. Aptalis Pharma US Inc., September 2012.

Page 583 4. Chey WD, Wong BCY, and the Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808-1825. 5. Omeclamox-Pak Prescribing Information. Pernix Therapeutics. February 2012.

Page 584 Progesterone Products

Prior Authorization Guideline

GL-11546 Progesterone Products

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 8/21/1998; CPS Revision Date: 10/14/2014

1 . Indications Drug Name: Crinone 8% (progesterone vaginal gel) Assisted Reproductive Technology Is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency.

Secondary Amenorrhea Is indicated for use in women who have failed to respond to treatment with Crinone 4%

Drug Name: Endometrin (progesterone vaginal insert) Assisted Reproductive Technology Is a progesterone indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an

Page 585 Assisted Reproductive Technology treatment program for infertile women.

Drug Name: Crinone 4% (progesterone vaginal gel) Secondary Amenorrhea Is indicated for the treatment of secondary amenorrhea.

Drug Name: Prometrium (progesterone oral capsules) Secondary Amenorrhea Is indicated for use in secondary amenorrhea.

Endometrial Hyperplasia Is indicated for use in the prevention of endometrial hyperplasia in nonhysterectomized postmenopausal women who are receiving conjugated estrogen tablets.

Drug Name: Progesterone Suppositories (extemporaneously compounded) Off Label Uses: Non-FDA Approved Product Is used as part of an Assisted Reproductive Technology program and are used to maintain pregnancy in patients who are at high risk for threatened abortions or recurrent miscarriages.

2 . Criteria

Product Name: Crinone 8% or Endometrin Diagnosis Assisted Reproductive Technology Approval Length 3 Month Guideline Type Prior Authorization

Approval Criteria

1 - To be used as part of an Assisted Reproductive Technology program

AND

2 - Not a benefit exclusion

Product Name: Crinone 8% Diagnosis Secondary Amenorrhea Approval Length 12 Month

Page 586 Guideline Type Prior Authorization

Approval Criteria

1 - For patients with secondary amenorrhea (the absence of menses in women who have already started menstruation who are not pregnant, breastfeeding, or in menopause)

AND

2 - History of failure, contraindication, or intolerance to Provera (medroxyprogesterone) or Aygestin (norethindrone)

Product Name: Progesterone Suppositories Diagnosis Assisted Reproductive Technology Approval Length 3 Month Guideline Type Non Formulary

Approval Criteria

1 - To be used as part of an Assisted Reproductive Technology program

AND

2 - Not a benefit exclusion

Product Name: Progesterone Suppositories Diagnosis Threatened Abortions/Recurrent Miscarriages Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - For high risk pregnancies

Page 587 AND

2 - Verification of pregnancy is necessary for each authorization

AND

3 - Not a benefit exclusion

Product Name: Crinone 4%, Brand Prometrium, or generic progesterone micronized capsule Diagnosis Secondary Amenorrhea Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - For patients with secondary amenorrhea (the absence of menses in women who have already started menstruation who are not pregnant, breastfeeding, or in menopause)

AND

2 - History of failure, contraindication, or intolerance to Provera (medroxyprogesterone) or Aygestin (norethindrone)

Product Name: Brand Prometrium or generic progesterone micronized capsule Diagnosis Prevention of Endometrial Hyperplasia in Patients Taking Hormone Therapy Approval Length 12 Month Guideline Type Non Formulary

Approval Criteria

1 - Patient is concurrently taking Estrogen Therapy [5,6]

3 . References

Page 588 1. Crinone Prescribing Information. Watson Pharma, Inc., August 2013. 2. Endometrin Prescribing Information. Ferring Pharmaceuticals, Inc., October 2012. 3. Prochieve Prescribing Information. Columbia Laboratories, Inc., October 2008. 4. Prometrium Prescribing Information. AbbVie, Inc., September 2013. 5. American Association of Clinical Endocrinologists (AACE). Medical guidelines for clinical practice for the diagnosis and treatment of menopause – AACE Menopause Guidelines Revision Task Force. Endocrine Pract. 2011; 17(Suppl 6): 1-25. 6. The North American Menopause Society. The 2012 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2012; 19(3): 257- 271. 7. Practice Committee of the American Society for Reproductive Medicine. Progesterone supplementation during luteal phase and in early pregnancy in the treatment of infertility: an educational bulletin. Fertil Steril. 2008;89(4):789-92.

Page 589 Proton Pump Inhibitors

Prior Authorization Guideline

GL-43294 Proton Pump Inhibitors

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 2/15/2011; P&T Revision Date: 10/26/2016. **Effective 1/1/2017** The following PPIs may be administered via a nasogastric tube: Dexilant capsules, Esomeprazole strontium capsules, Nexium capsules/oral suspension, Prevacid capsules/SoluTab, Prilosec capsules/oral suspension, Protonix oral suspension, and Zegerid oral suspension. The following PPIs may be administered via gastric tube: Nexium oral suspension, Prilosec oral suspension, Protonix oral suspension, and Zegerid oral suspension.

1 . Indications Drug Name: Aciphex (rabeprazole) Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) in Adults Indicated for the treatment of daytime and nighttime heartburn and other symptoms associated with GERD in adults.

Healing of Erosive or Ulcerative GERD in Adults Indicated for short-term (4 to 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative GERD. For those

Page 590 patients who have not healed after 8 weeks of treatment, an additional 8-week course of Aciphex may be considered.

Maintenance of Healing of Erosive or Ulcerative GERD in Adults Indicated for maintaining healing and reduction in relapse rates of heartburn symptoms in patients with erosive or ulcerative gastroesophageal reflux disease (GERD Maintenance). Controlled studies do not extend beyond 12 months.

Pathological Hypersecretory Conditions including Zollinger-Ellison Syndrome in Adults Indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults In combination with amoxicillin and clarithromycin as a three drug regimen, indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted.

Healing of Duodenal Ulcers in Adults Indicated for short-term (up to 4 weeks) treatment in the healing and symptomatic relief of duodenal ulcers. Most patients heal within 4 weeks.

Short-term Treatment of Symptomatic GERD in Adolescent Patients 12 years of Age and Older Indicated for the treatment of symptomatic GERD in adolescents 12 years of age and above for up to 8 weeks.

Treatment of GERD in Pediatric Patients 1 to 11 Years of Age Indicated for treatment of GERD in children 1 to 11 years of age for up to 12 weeks.

Drug Name: Dexilant (dexlansoprazole) Symptomatic Non-Erosive GERD Indicated for the treatment of heartburn associated with symptomatic non-erosive GERD for 4 weeks.

Healing of Erosive Esophagitis Indicated for healing of all grades of erosive esophagitis for up to 8 weeks.

Maintenance of Healed Erosive Esophagitis Indicated to maintain healing of erosive esophagitis and relief of heartburn for up to 6 months.

Drug Name: Esomeprazole strontium Healing of Erosive Esophagitis Indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis. For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4 to 8 week course of esomeprazole strontium may be considered.

Maintenance of Healing of Erosive Esophagitis Indicated to maintain symptom resolution and healing of erosive esophagitis. Controlled studies do not extend beyond 6 months.

Page 591

Symptomatic Gastroesophageal Reflux Disease Indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults.

Risk Reduction of NSAID-Associated Gastric Ulcer in Adults Indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk for developing gastric ulcers. Patients are considered to be at risk either due to their age (greater than or equal to 60) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults In combination with amoxicillin and clarithromycin, indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted.

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome in Adults Indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome.

Drug Name: Nexium (esomeprazole) Symptomatic GERD Indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults and children 1 year or older.

Healing of Erosive Esophagitis Indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis. For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4 to 8 week course of Nexium may be considered. In infants 1 month to less than 1 year, Nexium is indicated for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-medicated GERD.

Maintenance of Healing of Erosive Esophagitis Indicated to maintain symptom resolution and healing of erosive esophagitis. Controlled studies do not extend beyond 6 months.

Pathological Hypersecretory Conditions including Zollinger-Ellison Syndrome Indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence In combination with amoxicillin and clarithromycin, indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted.

Risk Reduction of NSAID-Associated Gastric Ulcer Indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk for

Page 592 developing gastric ulcers. Patients are considered to be at risk due to their age (greater than or equal to 60) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months.

Drug Name: Prevacid (lansoprazole) Short-Term Treatment of Active Duodenal Ulcer Indicated for short-term treatment (for 4 weeks) for healing and symptom relief of active duodenal ulcer.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence In combination with amoxicillin plus clarithromycin as triple therapy, indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. In combination with amoxicillin as dual therapy, indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Maintenance of Healed Duodenal Ulcers Indicated to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months.

Short-Term Treatment of Active Benign Gastric Ulcer Indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of active benign gastric ulcer.

Healing of NSAID-Associated Gastric Ulcer Indicated for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled studies did not extend beyond 8 weeks.

Risk Reduction of NSAID-Associated Gastric Ulcer Indicated for reducing the risk of NSAID- associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an NSAID. Controlled studies did not extend beyond 12 weeks.

Short-Term Treatment of Symptomatic GERD Indicated for the treatment of heartburn and other symptoms associated with GERD.

Maintenance of Healing of Erosive Esophagitis Indicated to maintain healing of erosive esophagitis. Controlled studies did not extend beyond 12 months.

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Short-Term Treatment of Erosive Esophagitis Indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of all grades of erosive esophagitis. For patients who do not heal with Prevacid for 8 weeks (5 to 10%), it may be helpful to give an additional 8 weeks of treatment. If there is a recurrence of erosive esophagitis, an additional 8-week course of Prevacid may be considered

Page 593 Drug Name: Prilosec (omeprazole) Duodenal Ulcer (adults) Indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy. In combination with clarithromycin and amoxicillin, indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults. In combination with clarithromycin, indicated for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Among patients who fail therapy, Prilosec with clarithromycin is more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted.

Gastric Ulcer (adults) Indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults.

Treatment of Symptomatic GERD (adults and pediatric patients) Indicated for the treatment of heartburn and other symptoms associated with GERD in pediatric patients and adults. The efficacy of Prilosec used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of GERD symptoms (eg, heartburn), additional 4 to 8 week courses of omeprazole may be considered.

Maintenance of Healing of Erosive Esophagitis (adults and pediatric patients) Indicated to maintain healing of erosive esophagitis in pediatric patients and adults. Controlled studies do not extend beyond 12 months.

Pathological Hypersecretory Conditions (adults) Indicated for the long-term treatment of pathological hypersecretory conditions (eg, Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.

Erosive Esophagitis (adults and pediatric patients) Indicated for the short-term treatment (4 to 8 weeks) of erosive esophagitis that has been diagnosed by endoscopy in pediatric patients and adults. The efficacy of Prilosec used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of erosive esophagitis, additional 4 to 8 week courses of omeprazole may be considered.

Drug Name: Protonix (pantoprazole) Short-Term Treatment of Erosive Esophagitis Associated With GERD Indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis. For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of Protonix may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established.

Maintenance of Healing of Erosive Esophagitis Indicated for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months.

Page 594

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Drug Name: Zegerid (omeprazole/sodium bicarbonate) Duodenal Ulcer Indicated for short-term treatment of active duodenal ulcer. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.

Gastric Ulcer Indicated for short-term treatment (4-8 weeks) of active benign gastric ulcer.

Symptomatic GERD Indicated for the treatment of heartburn and other symptoms associated with GERD. The efficacy of Zegerid used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, it may be helpful to give up to an additional 4 weeks of treatment. If there is recurrence of GERD symptoms (eg, heartburn), additional 4-8 week courses of Zegerid may be considered.

Maintenance of Healing of Erosive Esophagitis Indicated to maintain healing of erosive esophagitis. Controlled studies do not extend beyond 12 months.

Reduction of Risk of Upper Gastrointestinal Bleeding in CriticallyIll Patients (40 mg oral suspension only) Indicated for the reduction of risk of upper GI bleeding in critically ill patients.

Erosive Esophagitis Indicated for the short-term treatment (4 to 8 weeks) of erosive esophagitis which has been diagnosed by endoscopy. The efficacy of Zegerid used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, it may be helpful to give up to an additional 4 weeks of treatment. If there is recurrence of erosive esophagitis, additional 4-8 week courses of Zegerid may be considered.

2 . Criteria

Product Name: Brand Aciphex tablets, Generic rabeprazole tablets, Prilosec suspension, Brand Protonix tablets, Protonix suspension Diagnosis Once-daily PPI Therapy Guideline Type Step Therapy

Approval Criteria

1 - History of two of the following:

• Dexilant

Page 595 • omeprazole • pantoprazole

Product Name: Aciphex Sprinkle or Prevacid Solutab Diagnosis Once-daily PPI Therapy Guideline Type Step Therapy

Approval Criteria

1 - History of two of the following:

• Dexilant • omeprazole • pantoprazole

Product Name: Aciphex Sprinkle**, Brand Aciphex tablets**, Generic rabeprazole tablets**, Dexilant capsules, Esomeprazole strontium capsules**, Nexium capsules, Nexium suspension, Brand Prevacid capsules**, Generic lansoprazole capsules, Prevacid Solutab**, Brand Prilosec capsules**, Generic omeprazole capsules, Prilosec suspension**, Brand Protonix tablets**, Generic pantoprazole tablets, Protonix suspension**, Brand Zegerid capsules**, Generic omeprazole/sodium bicarbonate capsules**, First-Lansoprazole suspension**, or First- Omeprazole suspension** Diagnosis Twice-daily (BID) PPI Therapy*** Guideline Type Quantity Limit

Approval Criteria

1 - One of the following:

1.1 Failure of once-daily PPI regimen

1.2 One of the following diagnoses:

• Barrett's esophagus (with the need for complete acid control) [6] • Symptomatic GERD [6]

Page 596 • Presence of extraesophageal symptoms (exacerbation of cough or asthma, non-cardiac chest pain, dysphagia) [7] • Laryngopharyngeal reflux/spasm [9] • Zollinger-Ellison syndrome [8] • H. pylori eradication (esomeprazole, rabeprazole, omeprazole, lansoprazole, and pantoprazole only) [1, 2, 12, 13]*

AND

2 - One of the following:

2.1 Dose per day (mg/day) is supported in the dosage and administration section of the manufacturer's prescribing information

2.2 Dose per day (mg/day) is supported by one of the following compendia:

• American Hospital Formulary Service Drug Information • Micromedex DRUGDEX System

Notes Authorization of therapy will be issued for long-term for all diagnoses, e xcept for H. pylori eradication. For H. pylori eradication, authorization w ill be issued for 14 days. *Protonix has been used off-label for the treat ment of H.pylori eradication. [17] **These products may require step th erapy. ***Requests for greater than twice-daily dosing must be reviewe d using the Quantity Limit General Administrative Guideline.

3 . References

1. Aciphex Prescribing Information. Eisai Co., Ltd., November 2013. 2. Prilosec Prescribing Information. AstraZeneca Pharmaceuticals, October 2012. 3. Protonix Prescribing Information. Wyeth Pharmaceuticals, Inc., October 2012. 4. Zegerid Prescribing Information. Santarus, Inc., May 2011. 5. Caro JJ, Salas M, Ward A. Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials. Clin Ther. 2001 Jul;23(7):998-1017. 6. DeVault KR, Castell DO; American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2005 Jan;100(1):190-200. 7. Nord HJ. Extraesophageal symptoms: what role for the proton pump inhibitors? Am J Med. 2004 Sep 6;117 Suppl 5A:56S-62S.

Page 597 8. Metz DC, Soffer E, Forsmark CE, et al. Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion. Am J Gastroenterol. 2003 Feb;98(2):301-7. 9. Ford CN. Evaluation and management of laryngopharyngeal reflux. JAMA. 2005 Sep 28;294(12):1534-40. 10. American Gastroenterological Association (AGA) Medical position statement on the management of gastroesophageal reflux disease. Gastroenterology. 2008; 135:1383- 1391. 11. Dexilant Prescribing Information. Takeda Pharmaceuticals America, Inc., August 2013. 12. Nexium Prescribing Information. AstraZeneca Pharmaceuticals, November 2012. 13. Prevacid Prescribing Information. Takeda Pharmaceuticals, Inc., September 2012. 14. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-28. 15. First-Omeprazole Prescribing Information. CutisPharma, Inc., December 2011. 16. First-Lansoprazole Prescribing Information. CutisPharma, Inc., December 2011. 17. Gilbert DN, Moellering RC, Eliopoulos GM, Sande MA, eds. The Sanford Guide to Antimicrobial Therapy 2007. 37th ed. Sperryville, VA: Antimicrobial Therapy, Inc: 2007. 18. Esomeprazole strontium Prescribing Information. Amneal Pharmaceuticals, August 2013.

Page 598 Provigil (modafinil) and Nuvigil (armodafinil)

Prior Authorization Guideline

GL-80540 Provigil (modafinil) and Nuvigil (armodafinil)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 4/1/2021 P&T Approval Date: 1/1/2002 P&T Revision Date: 01/15/2020 ; 1/20/2021

1 . Indications Drug Name: Modafinil (Provigil*) and armodafinil (Nuvigil*) Narcolepsy, obstructive sleep apnea/hypopnea syndrome, shift work sleep disorder. To improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder

Drug Name: Modafinil Off Label Uses: Idiopathic hypersomnia, fatigue associated with multiple sclerosis, depression augmentation Has been shown to be beneficial in the treatment of excessive sleepiness in patients with idiopathic hypersomnia, treatment of fatigue associated with multiple sclerosis, and in the augmentation therapy for the treatment of depression.

2 . Criteria

Page 599 Product Name: Provigil* (modafinil) and Nuvigil* (armodafinil) Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - One of the following:

• Diagnosis of narcolepsy • Diagnosis of idiopathic hypersomnia • Diagnosis of excessive sleepiness due to obstructive sleep apnea • Diagnosis of excessive sleepiness due to shift work disorder • Diagnosis of fatigue associated with multiple sclerosis • For adjunctive therapy for the treatment of major depressive disorder or bipolar depression

Notes *Brand Provigil and Nuvigil are typically excluded from coverage. Tried/ failed criteria may be in place. Please refer to plan specifics to determi ne exclusion status.

Product Name: Provigil* (modafinil) and Nuvigil* (armodafinil) Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of positive clinical response to therapy Notes *Brand Provigil and Nuvigil are typically excluded from coverage. Tried/ failed criteria may be in place. Please refer to plan specifics to determi ne exclusion status.

3 . Background

Benefit/Coverage/Program Information

Page 600 Background:

Modafinil (Provigil*) and armodafinil (Nuvigil*) are wakefulness-promoting agents for oral administration. Both products are approved by the Food and Drug Administration (FDA) to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. Modafinil has been shown to be beneficial in the treatment of excessive sleepiness in patients with idiopathic hypersomnia, treatment of fatigue associated with multiple sclerosis, and in the augmentation therapy for the treatment of depression.

Additional Clinical Rules: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class • Supply limits may be in place. • *Brand Provigil and Nuvigil are typically excluded from coverage.Tried/Failed criteria may be in place.Please refer to plan specifics to determine exclusion status.

4 . References

1. Provigil [package insert]. Frazer, PA: Cephalon, Inc., July 2019. 2. Nuvigil [package insert]. Frazer, PA: Cephalon, Inc., July 2019. 3. Morgranthaler TI, Kapur VK, Brown T, et al. Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007;30(12)1705-116. 4. Rammohan KW, Rosenberg JH, Lynn DJ, et al. Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two center phase 2 study. J Neurol Neurosurg Psychiatry 2002;72:179-183. 5. Zifko UA, Rupp M, Schwarz S, et al. Modafinil in treatment of fatigue in multiple sclerosis. Results of an open-label study. J Neurol 2002;249:983-987. 6. Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH. Modafinil Augmentation Therapy in Unipolar and Bipolar Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Psychiatry 74:11, November 2013. 7. Practice guideline for the treatment of patients with major depressive disorder. Third edition. American Psychiatric Association. Arlington, VA. October 2010.

5 . Revision History

Date Notes

2/3/2021 Annual review. No changes.

Page 601 Quantity Limit General

Prior Authorization Guideline

GL-88346 Quantity Limit General

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 5/20/2008 P&T Revision Date: 11/14/2019 ; 08/13/2020 ; 7/21/2021

Note:

For all other drugs subject to quantity limits, OptumRx may authorize coverage for additional quantities of medications listed on the Standard QL list for patients who meet the following criteria.

1 . Criteria

Product Name: Less than or equal to the maximum dose as specified in the product prescribing information OR compendia for off-label uses (in the absence of a drug-specific guideline)* Approval Length 12 Months (except for titration of loading-dose purposes) Guideline Type Administrative

Page 602 Approval Criteria

1 - One of the following:

1.1 Quantity limit override requests must involve an FDA-approved indication

1.2 Quantity limit override requests involving off-label indications must meet off-label guideline approval criteria

AND

2 - One of the following:

2.1 For titration or loading-dose purposes (one time authorization)

2.2 Requested strength/dose is commercially unavailable

2.3 Patient is on a dose alternating schedule

2.4 For topical applications, patient requires a larger quantity to cover a larger surface area Notes Not to exceed maximum dose as specified in the product prescribing in formation or compendia for off-label uses. No override requests will be permitted for acetaminophen, alone or in combination with other agents , which will exceed a total of 4 grams of acetaminophen per day. *This guideline only applies in the absence of a drug-specific quantity limit ov erride guideline

Product Name: Greater than the maximum dose as specified in the product prescribing information OR compendia for off-label uses (in the absence of a drug-specific guideline)*

Page 603 Approval Length 12 month(s) Guideline Type Administrative

Approval Criteria

1 - One of the following:

1.1 Quantity limit override requests must involve an FDA-approved indication

1.2 Quantity limit override requests involving off-label indications must meet off-label guideline requirements

AND

2 - One of the following:

2.1 The maximum doses specified under the quantity restriction have been tried for an adequate period of time and been deemed ineffective in the treatment of the member's disease or medical condition

2.2 If lower doses have not been tried, there is clinical support (i.e., clinical literature, patient attributes, or characteristics of the drug) that the number of doses available under the quantity restriction will be ineffective in the treatment of the member's disease or medical condition

AND

3 - One of the following:**

3.1 Higher dose or quantity is supported in the dosage and administration section of the manufacturer's prescribing information

Page 604 3.2 Higher dose or quantity is supported by one of following compendia:

• American Hospital Formulary Service Drug Information • Micromedex DRUGDEX System

Notes *This guideline only applies in the absence of a drug-specific quantity li mit override guideline. No override requests will be permitted for aceta minophen, alone or in combination with other agents, which will exceed a total of 4 grams of acetaminophen per day. **NOTE: Published biom edical literature may be used as evidence to support safety and additio nal efficacy at higher than maximum doses for the diagnosis provided.

2 . Revision History

Date Notes

6/30/2021 Annual review - no changes

Page 605 Regranex (becaplermin gel)

Prior Authorization Guideline

GL-75653 Regranex (becaplermin gel)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 12/1/2020 P&T Approval Date: 1/1/2004 P&T Revision Date: 08/16/2019 ; 9/16/2020

1 . Indications Drug Name: Regranex (becaplermin gel) Lower extremity diabetic neuropathic ulcers Indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue, or beyond, and have an adequate blood supply. Regranex should be used as an adjunct to, and not a substitute for, good ulcer care practices including initial sharp debridement, pressure relief and infection control. The efficacy of Regranex gel has not been established for the treatment of pressure ulcers or venous stasis ulcers.

2 . Criteria

Product Name: Regranex Approval Length 6 month(s)

Page 606 Guideline Type Notification

Approval Criteria

1 - Patient has a lower extremity diabetic neuropathic ulcer

AND

2 - Treatment will be given in combination with ulcer wound care (e.g., debridement, infection control and/or pressure relief)

3 . Background

Benefit/Coverage/Program Information

Background:

Regranex is indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue, or beyond, and have an adequate blood supply. Regranex should be used as an adjunct to, and not a substitute for, good ulcer care practices including initial sharp debridement, pressure relief and infection control. The efficacy of Regranex gel has not been established for the treatment of pressure ulcers or venous stasis ulcers. If a member has a prescription for a diabetic medication within the last 180 days of claim’s history, the prescription for Regranex will automatically process.

Additional Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place.

4 . References

1. Regranex [package insert]. Fort Worth, Tx: Smith & Nephew, Inc; August 2019.

5 . Revision History

Page 607 Date Notes

10/19/2020 Annual review. References updated.

Page 608 Relistor (methylnaltrexone bromide) - PA/Med Nec

Prior Authorization Guideline

GL-71183 Relistor (methylnaltrexone bromide) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 2/26/2016 P&T Revision Date: 7/15/2020

1 . Indications Drug Name: Relistor (methylnaltrexone bromide) Opioid-induced constipation Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Relistor injection is also indicated for the treatment of opioid-induced constipation in patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.

2 . Criteria

Product Name: Relistor Injection [a] Approval Length 12 month(s)

Page 609 Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Relistor Injection will be approved based on documentation (e.g. chart notes) demonstrating one of the following:

1.1 Diagnosis of opioid induced constipation in patients with advanced illness receiving palliative care

1.2 Both of the following:

1.2.1 ONE of the following:

1.2.1.1 Diagnosis of opioid induced constipation with chronic, non-cancer pain

1.2.1.2 Diagnosis of opioid induced constipation in patients with chronic pain related to prior cancer diagnosis or cancer treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

AND

1.2.2 One of the following:

1.2.2.1 The patient is not able to swallow oral medications

1.2.2.2 History of failure, contraindication or intolerance to BOTH of the following:

1.2.2.2.1 An OTC laxative (document name and date tried)

Page 610 AND

1.2.2.2.2 Symproic Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Relistor Injection [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Relistor Injection therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Relistor Tablets*,[a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - ONE of the following:

1.1 Diagnosis of opioid induced constipation with chronic, non-cancer pain

1.2 Diagnosis of opioid induced constipation in patients with chronic pain related to prior cancer diagnosis or cancer treatment who do not require frequent (e.g., weekly) opioid dosage

Page 611 escalation

AND

2 - History of failure, contraindication or intolerance to BOTH of the following:

2.1 An OTC laxative (document name and date tried)

AND

2.2 Symproic Notes *Relistor tablets are typically excluded from coverage [a] State mandat es may apply. Any federal regulatory requirements and the member sp ecific benefit plan coverage may also impact coverage criteria. Other p olicies and utilization management programs may apply.

Product Name: Relistor Tablets*,[a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Relistor Tablet therapy Notes *Relistor tablets are typically excluded from coverage [a] State mandat es may apply. Any federal regulatory requirements and the member sp ecific benefit plan coverage may also impact coverage criteria. Other p olicies and utilization management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background:

Relistor (methylnaltrexone bromide) and Symporic (naldemedine) are opioid antagonists

Page 612 indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Relistor injection is also indicated for the treatment of opioid-induced constipation in patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care. Physicians and patients should periodically assess the need for continued treatment with Relistor.

4 . References

1. Relistor prescribing information. Bridgewater, NJ: Salix Pharmaceuticals, Inc.; November 2018. 2. Symproic [package insert]. Raleigh, NC: BioDelivery Sciences International. April 2019.

5 . Revision History

Date Notes

8/25/2020 Annual review. Updated initial authorization and references.

Page 613 Repatha (evolocumab) - PA/Med Nec

Prior Authorization Guideline

GL-90377 Repatha (evolocumab) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 5/20/2015 P&T Revision Date: 01/16/2019 ; 12/18/2019 ; 02/14/2020 ; 02/19/2021 ; 6/16/2021

1 . Indications Drug Name: Repatha (evolocumab) Hyperlipidemia Indicated as an adjunct to diet, alone or in combination with other lipid- lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C)¥

Homozygous familial hypercholesterolemia (HoFH) Indicated as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C [1]

Cardiovascular disease Indicated to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease

2 . Criteria

Page 614

Product Name: Repatha [a] Diagnosis Hyperlipidemia Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

1.1 Heterozygous familial hypercholesterolemia (HeFH) as confirmed by one of the following*¥:

1.1.1 Both of the following: [14-16]

1.1.1.1 Pre-treatment LDL-C greater than 190 mg/dL (greater than 155 mg/dL if less than 16 years of age)

AND

1.1.1.2 One of the following:

1.1.2 Both of the following: [14-16]

1.1.2.1 Pre-treatment LDL-C greater than 190 mg/dL (greater than 155 mg/dL if less than 16 years of age)

Page 615 AND

1.1.2.2 One of the following:

• Functional mutation in LDL, apoB, or PCSK9 gene* • Tendinous xanthomata • Arcus cornealis before age 45

1.2 Atherosclerotic cardiovascular disease (ASCVD) as confirmed by one of the following:

AND

2 - One of the following:

2.2 Both of the following:

2.2.1 Patient is unable to tolerate high-intensity statin as evidenced by one of the following intolerable and persistent (i.e. more than 2 weeks) symptoms:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations less than 10 times upper limit of normal [ULN])

AND

Page 616

2.2.2 One of the following:

2.3 Patient is unable to tolerate low or moderate-, and high-intensity statins as evidenced by one of the following:

2.3.1 One of the following intolerable and persistent (i.e. more than 2 weeks) symptoms for low or moderate-, and high-intensity statins:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations less than 10 times upper limit of normal [ULN])

2.3.2 Patient has a labeled contraindication to all statins

2.3.3 Patient has experienced rhabdomyolysis or muscle symptoms with statin treatment with CK elevations greater than 10 times ULN

AND

Page 617 3 - One of the following:

3.1 One of the following LDL-C values while on maximally tolerated lipid lowering therapy for a minimum of at least 12 weeks within the last 120 days:

• LDL-C greater than or equal to 100 mg/dL with ASCVD • LDL-C greater than or equal to 130 mg/dL without ASCVD

3.2 Both of the following:

3.2.1 One of the following LDL-C values while on maximally tolerated lipid lowering therapy for a minimum of at least 12 weeks within the last 120 days:

• LDL-C between 70 mg/dL and 99 mg/dL with ASCVD • LDL-C between 100 mg/dL and 129 mg/dL without ASCVD

AND

3.2.2 One of the following:

AND

4 - Used as an adjunct to a low-fat diet and exercise

AND

5 - Not used in combination with another proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor [e.g., Praluent (alirocumab)]

AND

6 - Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and

Page 618 request the medical information necessary to verify the accuracy of the information provided Notes *Results of prior genetic testing can be submitted as confirmation of dia gnosis of HeFH, however please note that UnitedHealthcare does not c urrently cover genetic testing for evidence of an LDL-receptor mutation, familial defective apo B-100 or a PCSK9 mutation. ¥ No coverage of R epatha will be provided for the primary prevention of cardiovascular ev ents and/or for the lowering of low-density lipoprotein cholesterol in pati ents with primary hyperlipidemia who do not have heterozygous familia l hypercholesterolemia or established atherosclerotic cardiovascular di sease (ASCVD) as the use of PCSK9 inhibitors in this population is not supported by the 2018 American College of Cardiology/ American Hea rt Association Cholesterol Clinical Practice Guidelines. [a] State manda tes may apply. Any federal regulatory requirements and the member sp ecific benefit plan coverage may also impact coverage criteria. Other p olicies and utilization management programs may apply.

Product Name: Repatha [a] Diagnosis Hyperlipidemia Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient continues to receive statin at maximally tolerated dose (unless patient has an inability to take statins)

AND

2 - Patient is continuing a low-fat diet and exercise regimen

AND

3 - Documentation of a positive clinical response to therapy from pre-treatment baseline

AND

4 - Not used in combination with another proprotein convertase subtilisin/kexin type 9 (PCSK9)

Page 619 inhibitor [e.g., Praluent (alirocumab)]

AND

5 - Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Repatha [a] Diagnosis Homozygous Familial Hypercholesterolemia Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of homozygous familial hypercholesterolemia (HoFH) as confirmed by both of the following:*

1.1 One of the following:

• Pre-treatment LDL-C greater than 500 mg/dL • Treated LDL-C greater than 300 mg/dL

AND

1.2 One of the following:

• Xanthoma before 10 years of age • Evidence of heterozygous familial hypercholesterolemia (HeFH) in both parents

AND

Page 620 2 - Used as an adjunct to a low-fat diet and exercise

AND

3 - Patient is receiving other lipid-lowering therapy (e.g., statin, ezetimibe, LDL apheresis)

AND

4 - Not used in combination with another proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor [e.g., Praluent (alirocumab)]

AND

5 - Not used in combination with Juxtapid (lomitapide)

AND

6 - Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided Notes *Results of prior genetic testing can be submitted as confirmation of dia gnosis of HoFH, however please note that UnitedHealthcare does not c urrently cover genetic testing for evidence of an LDL-receptor mutation, familial defective apo B-100 or a PCSK9 mutation. [a] State mandates may apply. Any federal regulatory requirements and the member specif ic benefit plan coverage may also impact coverage criteria. Other polici es and utilization management programs may apply.

Product Name: Repatha [a] Diagnosis Homozygous Familial Hypercholesterolemia Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Page 621

1 - Patient is continuing a low-fat diet and exercise regimen

AND

2 - Patient continues to receive other lipid-lowering therapy (e.g., statin, LDL apheresis)

AND

3 - Documentation of a positive clinical response to therapy from pre-treatment baseline

AND

4 - Not used in combination with another proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor [e.g., Praluent (alirocumab)]

AND

5 - Not used in combination with Juxtapid (lomitapide)

AND

3 . Background

Benefit/Coverage/Program Information

Page 622 Background:

Repatha™ (evolocumab) is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody indicated :

• to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease • as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C)¥ • as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C1

Additional Clinical Rules: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class • Supply limits may be in place • Step Therapy may be in place.

4 . References

1. Repatha [package insert]. Thousand Oaks, CA : Amgen Inc.; February 2021. 2. WHO Familial Hypercholesterolemia Consultation Group. Familial Hypercholesterolemia (FH): report of a second WHO consultation. Geneva: World Health Organization; 1999. 3. Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ. 1991;303:893-6. 4. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-934. 5. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015a; DOI: 10.1056/NEJMoa1410489 [Epub ahead of print]. 6. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251:365-74. 7. ATP III Final Report PDF. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421 8. Per clinical drug consult with cardiologist. August 3, 2015. 9. Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370:1809-19. 10. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223:262-8.

Page 623 11. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double- blind, placebo-controlled trial. Lancet. 2015;385:341-50. 12. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercohlesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35:2146-57. 13. Lloyd-Jones D, Morris P, Ballantyne C, et al. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholersterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2016;68:92-125. 14. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. American journal of epidemiology. 2004;160:407-420 15. Haase A, Goldberg AC. Identification of people with heterozygous familial hypercholesterolemia. Current opinion in lipidology. 2012;23:282-289. 16. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. European heart journal. 2013;34:3478-3490a. 17. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017; Suppl 2;23:1-87. 18. Lloyd-Jones D, Morris P, Ballantyne C, et al. 2017 Focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL- cholersterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2017. 19. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; DOI: 10.1161/CIR.0000000000000625.

5 . Revision History

Date Notes

7/26/2021 Aligned language to step therapy program. Removed prescriber specia list requirement. Removed submission of medical records requirement throughout criteria. Changed initial authorization duration to 12 months to align all PCSK9 programs. Updated reference.

Page 624 Rexulti (brexpiprazole) - PA/Med Nec

Prior Authorization Guideline

GL-68967 Rexulti (brexpiprazole) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2020 P&T Approval Date: 2/17/2017 P&T Revision Date: 6/17/2020

1 . Indications Drug Name: Rexulti (brexpiprazole) Major Depressive Disorder (MDD) FDA approved for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). The use of adjunctive atypical antipsychotics in the treatment of major depressive disorder is reserved for those who fail to demonstrate response to adequate trials of antidepressant monotherapy.

Schizophrenia FDA approved for the treatment of schizophrenia. For the treatment of schizophrenia, the selection of which antipsychotic medication to use for an individual patient with schizophrenia should be made based on patient clinical factors and the side effect profiles of antipsychotic drugs. With the exception of clozapine for patients with refractory symptoms, there is not convincing evidence to favor one antipsychotic over the others based on efficacy.

2 . Criteria

Page 625 Product Name: Rexulti [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Submission of medical records documenting ALL of the following:

1.1.1 The patient has a diagnosis of schizophrenia

AND

1.1.2 The patient has a history of failure, contraindication or intolerance to a trial of aripiprazole. (Document date and duration of trial).

AND

1.1.3 The patient has a history of failure, contraindication or intolerance to a trial of at least TWO of the following atypical antipsychotics. (Document drug, date and duration of trial):

• risperidone • quetiapine IR or XR • ziprasidone • olanzapine

1.2 Submission of medical records documenting ALL of the following:

1.2.1 The patient has a diagnosis of major depressive disorder

AND

1.2.2 Rexulti is being used in combination with an antidepressant medication.

Page 626

AND

1.2.3 The patient has a history of failure, contraindication or intolerance to a trial of at least one selective serotonin reuptake inhibitor (SSRI). (Document drug, date and duration of trial).

AND

1.2.4 The patient has a history of failure, contraindication or intolerance to a trial of at least one serotonin norepinephrine reuptake inhibitor (SNRI), mirtazapine, or bupropion. (Document drug, date and duration of trial).

AND

1.2.5 The patient has a history of failure, contraindication or intolerance to a trial of at least one of the following atypical antipsychotics approved by the FDA for the adjunctive treatment of major depressive disorder with an antidepressant (Document drug, date and duration of trial):

• olanzapine • aripiprazole • quetiapine extended-release

1.3 Treatment with Rexulti was initiated at a recent behavioral inpatient admission (discharge within the past 3 months) and the member is currently stable on therapy. (Document date of discharge from inpatient admission).

1.4 Both of the following:

1.4.1 Patient is currently on Rexulti therapy

AND

1.4.2 Patient has not received a manufacturer supplied sample at no cost in the prescriber’s

Page 627 office, or any form of assistance from the manufacturer (e.g., sample card which can be redeemed at a pharmacy for a free supply of medication) as a means to establish as a current user of Rexulti*

1.5 All of the following:

1.5.1 Patient is currently on Rexulti therapy

AND

1.5.2 Patient has received a manufacturer supplied sample at no cost in the prescriber’s office, or any form of assistance from the manufacturer (e.g., sample card which can be redeemed at a pharmacy for a free supply of medication) as a means to establish as a current user of Rexulti

AND

1.5.3 Provider attests switching to an alternative preferred agent could lead to deterioration of the patient’s condition requiring emergent medical care. Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Patients requesting initial authorization who were established on th erapy via the receipt of a manufacturer supplied sample at no cost in th e prescriber’s office or any form of assistance from the manufacturer s hall be required to meet initial authorization criteria as if patient were n ew to therapy, unless provider attests to the risk of deterioration with a change in medication.

Product Name: Rexulti [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Page 628 1 - Documentation of positive clinical response to Rexulti Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Programs:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class • Supply limits may be in place. • Prior Authorization/Step Therapy may be in place.

4 . References

1. Rexulti [package insert]. Rockville, MD: Otsuka America Pharmaceutical, Inc; March 2020. 2. Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 2010; 36:71. 3. Stroup TS, Marder S. Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UptoDate. April 2020. 4. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia Second Edition. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizop hrenia.pdf 5. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines

5 . Revision History

Date Notes

7/14/2020 Annual review. Updated references.

Page 629

Page 630 Rexulti (brexpiprazole) - Step Therapy

Prior Authorization Guideline

GL-90383 Rexulti (brexpiprazole) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 11/18/2015 P&T Revision Date: 03/18/2020 ; 6/16/2021

1 . Indications Drug Name: Rexulti (brexpiprazole) Schizophrenia FDA approved for the treatment of schizophrenia.

Major depressive disorder (MDD) FDA approved for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD).

2 . Criteria

Product Name: Rexulti [a] Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 631 Guideline Type Step Therapy

Approval Criteria

1 - One of the following:

1.1 Diagnosis of schizophrenia and history of failure, contraindication, or intolerance to both of the following:

1.1.1 aripiprazole (Document date and duration tried)

AND

1.1.2 At least one of the following (Document date, duration and drug tried):

• risperidone • olanzapine • quetiapine IR or XR • ziprasidone

1.2 Diagnosis of major depressive disorder, and used in combination with an antidepressant, and history of failure, contraindication, or intolerance to all of the following:

1.2.1 At least one selective serotonin reuptake inhibitor (SSRI) (Document date, duration and drug tried)

AND

1.2.2 At least one of the following: serotonin norepinephrine reuptake inhibitor (SNRI), mirtazapine, or bupropion (Document date, duration and drug tried)

AND

1.2.3 At least one of the following atypical antipsychotics approved by the FDA for the adjunctive treatment of major depressive disorder with an antidepressant (Document drug, date and duration tried):

Page 632 • olanzapine • aripiprazole • quetiapine extended-release

1.4 All of the following:

• The member is new to the plan (as evidenced by coverage effective date of less than or equal to 120 days) • The member is currently stabilized on Rexulti

1.5 All other diagnoses (not specified above):

1.5.1 History of failure, contraindication or intolerance to aripiprazole and quetiapine. (Document the diagnosis, date and duration of trial for each preferred product). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Rexulti [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Step Therapy

Approval Criteria

1 - Documentation of positive clinical response.

Page 633 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. Rexulti (brexpiprazole) is FDA approved for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) and for the treatment of schizophrenia.

For the treatment of schizophrenia, treatment guidelines recommend the use of any atypical antipsychotic (with the exception of clozapine) as first-line. The use of adjunctive atypical antipsychotics in the treatment of major depressive disorder is reserved for those who fail to demonstrate response to adequate trials of antidepressant monotherapy.

This program requires a member to try two atypical antipsychotics (aripiprazole plus the choice of at least one of the following: risperidone, olanzapine, ziprasidone, quetiapine IR or Seroquel XR) before providing coverage for Rexulti for schizophrenia. For major depressive disorder, this program requires the trial of two adequate antidepressant trials (at least two trials from different antidepressant classes) as well as Seroquel XR prior to the coverage of Rexulti. If a member has a prescription for Rexulti in the claims history within the previous 12 months, the claim will automatically process.

Additional Clinical Programs:

• Supply limits may also be in place. • Prior Authorization/Medical Necessity may be in place. • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Rexulti [package insert]. Rockville, MD: Otsuka Pharmaceutical Co.; March 2020.

Page 634 2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia Second Edition. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizop hrenia.pdf 3. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. Available at: https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.p df 4. Nelson, C. Unipolar depression in adults: Treatment with second-generation antipsychotics. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on May 4, 2021).

5 . Revision History

Date Notes

7/26/2021 Annual review. Updated references.

Page 635 Reyvow (lasmiditan) - PA/Med Nec

Prior Authorization Guideline

GL-90716 Reyvow (lasmiditan) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 3/18/2020 P&T Revision Date: 07/15/2020 ; 02/19/2021 ; 7/21/2021

1 . Indications Drug Name: Reyvow (lasmiditan) Migraine with or without aura Indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: Reyvow is not indicated for the preventive treatment of migraine.

2 . Criteria

Product Name: Reyvow [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 636

Approval Criteria

1 - All of the following:

1.1 Used for acute treatment of migraine

AND

1.2 Patient is 18 years of age or older

AND

1.3 History of a therapeutic failure (after at least 3 migraine episodes and a minimum of a 30- day trial), contraindication or intolerance to two of the following (document name and date tried):

• almotriptan (Axert) • eletriptan (Relpax) • frovatriptan (Frova) • naratriptan (Amerge) • rizatriptan (Maxalt/Maxalt MLT) • sumatriptan (Imitrex) • zolmitriptan (Zomig)

AND

1.4 Prescribed by or in consultation with one of the following specialists with expertise in the acute treatment of migraine:

• Neurologist • Pain Specialist • Headache Specialist [b]

AND

1.5 Prescriber attests to ALL of the following:

1.5.1 Patient has been informed the use of Reyvow may result in significant CNS impairment, and may impact the patient’s ability to drive or operate machinery for 8 hours after each dose

Page 637

AND

1.5.2 If used concurrently with a benzodiazepine or other drugs that could potentially cause central nervous system (CNS) depression, the prescriber has acknowledged that they have completed an assessment of increased risk for sedation and other cognitive and/or neuropsychiatric adverse events

AND

1.5.3 The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided

AND

1.6 One of the following:

1.6.1 Patient is currently treated with one of the following prophylactic therapies:

1.6.2 Patient has less than 4 migraine days per month

1.6.3 Patient has greater than or equal to 4 migraine days per month and has contraindication or intolerance to one of the following prophylactic therapies:

Page 638 • Amitriptyline (Elavil) • A beta-blocker (i.e., atenolol, metoprolol, nadolol, propranolol, or timolol) • A biologic calcitonin gene-related peptide receptor (CGRP) antagonist for preventive treatment of migraine [i.e., Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Vyepti (eptinezumab-jjmr)] • Divalproex sodium (Depakote/Depakote ER) • OnabotulinumtoxinA (Botox) [c] • Topiramate (Topamax) • Venlafaxine (Effexor/Effexor XR)

Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. [b] Headache specialists are physicians certified by the United Coun cil for Neurologic Subspecialties (UCNS). [c] Coverage of onabotulinu mtoxinA (Botox) may be subject to additional benefit and coverage revi ew requirements.

Product Name: Reyvow [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Benefit/Coverage/Program Information

Background:

Page 639 Reyvow (lasmiditan) is a serotonin 5-HT1F receptor agonist indicated for the acute treatment of migraine with or without aura in adults. Sedation was reported up to 8 hours after a single dose of Reyvow. Patients should be advised to not engage in activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, for at least 8 hours after each dose of Reyvow.

The American Headache Society recommends use of NSAIDs (including aspirin), non- opioid analgesics, acetaminophen, or caffeinated analgesic combinations (e.g., aspirin/acetaminophen/caffeine) for mild‐to‐moderate attacks and migraine‐specific agents (i.e., triptans, dihydroergotamine [DHE]) for moderate or severe attacks and mild‐to‐moderate attacks that respond poorly to NSAIDs or caffeinated combinations.

This program requires a member to try two generic triptans prior to receiving coverage for Reyvow. Additional Clinical Programs:

• Supply limits may apply. • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Reyvow [package insert]. Indianapolis, IN: Lilly USA, LLC; January 2020. 2. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache: The Journal of Head and Face Pain. 2019:59; 1-18.

5 . Revision History

Date Notes

8/5/2021 Updated the trial language to include 3 migraine episodes. Updated ref erences.

Page 640 Sedative Hypnotic Agents - Step Therapy

Prior Authorization Guideline

GL-88416 Sedative Hypnotic Agents - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 8/1/2021 P&T Approval Date: 8/1/2008 P&T Revision Date: 04/15/2020 ; 10/21/2020 ; 10/21/2020 ; 5/21/2021

1 . Criteria

Product Name: Belsomra, Dayvigo, or Zolpimist [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of trial and failure of at least 2 weeks, contraindication, or intolerance to two of the following sedative-hypnotic alternatives:

• Zolpidem (generic Ambien) • Zaleplon (generic Sonata)

Page 641 • Eszopiclone (generic Lunesta)

Product Name: ramelteon (generic Rozerem*) [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - One of the following:

1.1 History of trial and failure of at least 2 weeks, contraindication, or intolerance to two of the following sedative-hypnotic alternatives:

• Zolpidem (generic Ambien) • Zaleplon (generic Sonata) • Eszopiclone (generic Lunesta)

1.2 History of or potential for a substance abuse disorder Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. *Brand Rozerem is typically excluded from coverage

Product Name: Rozerem* [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - Both of the following:

Page 642 1.1 History of trial and failure of at least 2 weeks, contraindication, or intolerance to two of the following sedative-hypnotic alternatives:

• Zolpidem (generic Ambien) • Zaleplon (generic Sonata) • Eszopiclone (generic Lunesta)

AND

1.2 History of trial and failure of at least 2 weeks, contraindication, or intolerance to ramelteon (generic Rozerem)

2 - Both of the following:

2.1 History of or potential for a substance abuse disorder

AND

2.2 History of trial and failure of at least 2 weeks, contraindication, or intolerance to ramelteon (generic Rozerem) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. •*Brand Rozerem is typically excluded from coverage

2 . Background

Benefit/Coverage/Program Information

Background:

Step Therapy programs are utilized to encourage use of lower cost alternatives for certain therapeutic classes. This program requires a member to try a lower cost sedative hypnotic agent before providing coverage for Belsomra, Dayvigo, Rozerem* or Zolpimist. There will be exceptions if the patient has had an inadequate response or is intolerant to the lower cost sedative hypnotic agent. If a member has a prescription for two of the first step sedative

Page 643 hypnotics in claims history within the previous 12 months, the prescription for Belsomra, Dayvigo, ramelteon or Zolpimist will automatically process.

Other Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply Limits may be in place. • *Brand Rozerem is typically excluded from coverage.

3 . References

1. Belsomra [package insert]. Whitehouse Station, NJ: Merck & Co. March 2020. 2. Rozerem [package insert]. Deerfield, IL: Takeda Global. December 2018. 3. Zolpimist [package insert]. Englewood, CO: Aytu BioScience, Inc; August 2019. 4. Dayvigo [package insert]. Woodcliff Lake, NJ: Easai Inc; April 2020.

4 . Revision History

Date Notes

6/30/2021 Updated criteria to note brand Rozerem is typically excluded from cove rage and will require a step through the generic. Updated references.

Page 644 Selzentry (maraviroc)

Prior Authorization Guideline

GL-81814 Selzentry (maraviroc)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 1/1/2012 P&T Revision Date: 02/15/2019 ; 02/14/2020 ; 2/19/2021

1 . Indications Drug Name: Selzentry (maraviroc) CCR5-tropic HIV-1 Indicated for combination antiretroviral treatment of patients 2 years of age and older infected with only CCR5-tropic HIV-1.

2 . Criteria

Product Name: Selzentry Diagnosis CCR5-tropic HIV-1 Approval Length 24 month(s) Guideline Type Notification

Page 645

Approval Criteria

1 - Patient has CCR5-tropic HIV-1 infection as confirmed by a highly sensitive tropism assay

AND

2 - Patient is currently taking or will be prescribed an optimized background antiretroviral therapy regimen

3 . Background

Benefit/Coverage/Program Information

CCR5-tropic HIV-1

Selzentry (maraviroc) is a CCR5 co-receptor antagonist indicated for combination antiretroviral treatment of patients 2 years of age and older infected with only CCR5-tropic HIV-1. Tropism testing with a highly sensitive tropism assay is required for the appropriate use of Selzentry. [1]

4 . References

1. Selzentry [Package Insert]. Research Triangle Park, NC: ViiV Healthcare; July 2018.

5 . Revision History

Date Notes

3/4/2021 Annual review. No changes to coverage criteria.

Page 646 Sensipar (cinacalcet) - PA/Med Nec

Prior Authorization Guideline

GL-73252 Sensipar (cinacalcet) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 8/19/2016 P&T Revision Date: 08/16/2019 ; 08/16/2019 ; 8/14/2020

1 . Indications Drug Name: Sensipar (cinacalcet) Secondary hyperparathyroidism Indicated for the treatment of secondary hyperparathyroidism (HPT) in patients with chronic kidney disease on dialysis.

Parathyroid carcinoma Indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma.

Primary hyperparathyroidism Indicated for the treatment of hypercalcemia in patients with primary HPT for whom parathryoidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy.

2 . Criteria

Page 647 Product Name: Sensipar [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Prescribed by or in consultation with an oncologist, endocrinologist, or nephrologist

AND

2 - One of the following:

2.1 All of the following:

2.1.1 Diagnosis of secondary hyperparathyroidism with chronic kidney disease

AND

2.1.2 Patient is on dialysis

AND

2.1.3 Both of the following:

• Patient has therapeutic failure, contraindication or intolerance to one phosphate binder (e.g., PhosLo, Fosrenol, Renvela, Renagel, etc.) • Patient has therapeutic failure, contraindication or intolerance to one vitamin D analog (e.g., calcitriol, Hectorol, Zemplar, etc.)

2.2 Diagnosis of hypercalcemia with parathyroid carcinoma

Page 648 2.3 Both of the following:

• Diagnosis of severe hypercalcemia (level greater than 12.5 mg/dL) with primary hyperparathyroidism • Patient is unable to undergo parathyroidectomy

Product Name: Sensipar [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient has experienced a reduction in serum calcium from baseline Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . References

1. Sensipar Prescribing Information. Amgen Inc., Thousand Oaks, CA. December 2019. 2. Marcocci C1, Bollerslev J, Khan AA, Shoback DM. Medical management of primary hyperparathyroidism: proceedings of the fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2014 Oct;99(10):3607-18. doi: 10.1210/jc.2014-1417. Epub 2014 Aug 27. 3. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB. KDIGO 2017 Clinical Practice Guideline Update For The Diagnosis, Evaluation, Prevention, And Treatment Of Chronic Kidney Disease–Mineral And Bone Disorder (CKD-MBD) Ann Intern Med. 2018 Mar 20;168(6):422-430.

4 . Revision History

Page 649 Date Notes

9/11/2020 Annual review with no change to coverage criteria. Updated reference.

Page 650 Short-Acting Opioid Review Criteria for opioid naïve members

Prior Authorization Guideline

GL-87159 Short-Acting Opioid Review Criteria for opioid naïve members

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 12/20/2017 P&T Revision Date: 04/15/2020 ; 4/21/2021

1 . Criteria

Product Name: Short-Acting Opioids [a] Approval Length Up to 24 months for cancer, end of life or palliative care pain; 1 month for all others Guideline Type Supply Limit

Approval Criteria

1 - Opioid naïve members (defined as not having filled an opioid in the past 120 days) may receive greater than the supply limit* based on ALL of the following:

1.1 One of the following:

Page 651

1.1.1 Cancer diagnosis

1.1.2 End- of- life pain, including hospice care

1.1.3 Palliative care

1.1.4 Sickle cell anemia

1.1.5 Both of the following:

1.1.5.1 One of the following:

• Traumatic injury • Post-surgical procedures, excluding dental procedures • Prescriber attests the patient has received an opioid in the past 120 days.

AND

1.1.5.2 Prescriber attests to both of the following:

• The information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided. • If requested for traumatic injury or post-surgical procedure, prescriber attests that based on the injury or surgical procedure performed the member requires greater than a 7 day supply* of short-acting opioids to adequately control pain.

AND

Page 652

1.2 If the request is for 50 MME or greater, one of the following:

1.2.1 Diagnosis of cancer, end of life pain (including hospice care), palliative care or sickle cell anemia

1.2.2 Patient is currently at or exceeding 50 MME and prescriber attests patient has been on an opioid in the past 120 days

1.2.3 Document all of the following:

• The diagnosis associated with the need for pain management with opioids • If used in patients with medical comorbidities or if used concurrently with a benzodiazepine or other drugs that could potentially cause drug-drug interactions, the prescriber has acknowledged that they have completed an assessment of increased risk for respiratory depression • The prescriber has acknowledged that they have completed an addiction risk and risk of overdose assessment • Prescriber attests the member requires more than 50 MME per day to adequately control pain. (please note initial fill will be limited to 90 MME)

AND

1.3 Request does not exceed four grams of acetaminophen per day. Notes Authorization for cancer, end of life pain or palliative care pain or sickle cell anemia will be issued or a quantity of 9999 for 24 months to preve nt further disruption in therapy if the patient’s dose is increased. Memb ers new to plan (coverage effective date of <120 days) will be approve d for one month for the requested MME not to exceed the plan’s supply limit. All other approvals will be issued for one month for the requested MME not to exceed the maximum labeled FDA dosing where a maxim um exists, the plan’s supply limit OR 90 MME. [a] State mandates may apply. Any federal regulatory requirements and the member specific be nefit plan coverage may also impact coverage criteria. Other policies a nd utilization management programs may apply. * Patients age 19 year s and under new to opioid therapy are restricted to a 3-day supply for i nitial fill. Members age 20 years and older new to opioid therapy are re stricted to up to a 7-day supply for initial fill. Initial fill for all ages is limit ed to <50 MME.

Page 653

2 . Background

Benefit/Coverage/Program Information

Background:

The Center for Disease Control (CDC) recommends that clinicians should prescribe the lowest effective dosage when opioids are started. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to 50 morphine milligram equivalents (MME) or more per day, and should avoid increasing dosage to 90 MME or more per day or carefully justify a decision to titrate dosage to 90 MME or more per day.

Patients new to opioid therapy will be limited to a 7 day supply* and less than 50 MME per day. Opioid naïve members are defined as not having filled an opioid in the past 120 days.

* Patients age 19 years and under new to opioid therapy are restricted to a 3-day supply for initial fill. Members age 20 years and older new to opioid therapy are restricted to up to a 7-day supply for initial fill. Initial fill for all ages is limited to <50 MME.

Additional Clinical Programs

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place. • Opioid Cumulative Dose Review may be in place.

EI 90 MME Table for Drug Name and Strength 49 MME 90 MME Equivalent Equivalent (Max units/day) (Max units/day)

ACETAMINOPHEN-CAFFEINE- 12 capsules/day Requests over 49 MME exceed the DIHYDROCODEINE CAP 320.5-30- FDA max. 16 MG

ACETAMINOPHEN-CAFFEINE- 12 tablets/day Requests over 49 MME exceed the DIHYDROCODEINE TAB 325-30-16 FDA max. MG

ACETAMINOPHEN W/ CODEINE 136mL/day 250mL/day. Plan's supply limit from the master supply limit grid is more

Page 654 SOLN 120-12 MG/5ML restrictive.

ACETAMINOPHEN W/ CODEINE 13 tablets/day Requests over 49 MME exceed the TAB 300-15 MG FDA max.

CARISOPRODOL W/ ASPIRIN & 8 tablets/day Requests over 49 MME exceed the CODEINE TAB 200-325-16 MG FDA max.

CODEINE SULFATE TAB 15 MG 21 tablets/day 40 tablets/day. FDA max dose is 24 tablets/day. 90 MME/plan supply limit will exceed FDA max.

CODEINE SULFATE TAB 30 MG 10 tablets/day 20 tablets/day. FDA max dose is 12 tablets/day. 90 MME/plan supply limit will exceed FDA max.

CODEINE SULFATE TAB 60 MG 5 tablets/day 10 tablets/day. FDA max dose is 6 tablets/day. 90 MME/plan supply limit will exceed FDA max.

DEMEROL (MEPERIDINE HCL) 9 tablets/day 18 tablets/day TAB 50 MG

DEMEROL (MEPERIDINE HCL) 4 tablets/day 9 tablets/day TAB 100 MG

DILAUDID (HYDROMORPHONE 12.25mL/day 22.5mL/day HCL) LIQD 1 MG/ML

DILAUDID (HYDROMORPHONE 6 tablets/day 11 tablets/day HCL) TAB 2 MG

DILAUDID (HYDROMORPHONE 3 tablets/day 5 tablets/day HCL) TAB 4 MG

DILAUDID (HYDROMORPHONE 1 tablet/day 2 tablets/day HCL) TAB 8 MG

HYCET (HYDROCODONE- 98mL/day 180mL/day ACETAMINOPHEN) SOLN 7.5-325 MG/15ML

HYDROCODONE- 12 tablets/day Requests over 49 MME exceed the ACETAMINOPHEN TAB 2.5-325 FDA max. MG

HYDROCODONE- 4 tablets/day 9 tablets/day ACETAMINOPHEN TAB 10-300 MG

Page 655 HYDROCODONE-IBUPROFEN TAB 9 tablets/day Requests over 49 MME exceed the 5-200 MG FDA max.

HYDROCODONE-IBUPROFEN TAB 6 tablets/day Requests over 49 MME exceed the 7.5-200 MG FDA max.

HYDROCODONE-IBUPROFEN TAB 4 tablets/day 9 tablets/day. FDA max dose is 5 10-200 MG tablets/day. 90 MME/plan supply limit will exceed FDA max.

HYDROMORPHONE HCL SUPPOS 4 7 suppositories/day 3 MG suppositories/day

LORTAB (HYDROCODONE- 73.5mL/day 135mL/day ACETAMINOPHEN) SOLN 10-300 MG/15ML

MEPERIDINE HCL ORAL SOLN 50 49mL/day 90mL/day MG/5ML

MEPERIDINE W/ PROMETHAZINE 9 capsules/day Requests over 49 MME exceed the CAP 50-25 MG FDA max.

MORPHINE SULFATE ORAL SOLN 24.5mL/day 45mL/day 10 MG/5ML

MORPHINE SULFATE ORAL SOLN 12.25mL/day 22.5mL/day 20 MG/5ML

MORPHINE SULFATE ORAL SOLN 2.4mL/day 4.5mL/day 100 MG/5ML (20 MG/ML)

MORPHINE SULFATE SUPPOS 5 9 18 suppositories/day MG suppositories/day

MORPHINE SULFATE SUPPOS 10 4 9 suppositories/day MG suppositories/day

MORPHINE SULFATE SUPPOS 20 2 4 suppositories/day MG suppositories/day

MORPHINE SULFATE SUPPOS 30 1 suppository/day 3 suppositories/day MG

MORPHINE SULFATE TAB 15 MG 3 tablets/day 6 tablets/day

MORPHINE SULFATE TAB 30 MG 1 tablet/day 3 tablets/day

NALOCET TAB 2.5-300 13 tablets/day Requests over 49 MME exceed the

Page 656 FDA max.

NORCO (HYDROCODONE- 9 tablets/day 18 tablets/day. Plan's supply limit from ACETAMINOPHEN) TAB 5-325 MG the master supply limit grid is more restrictive.

NORCO (HYDROCODONE- 4 tablets/day 9 tablets/day ACETAMINOPHEN) TAB 10-325 MG

NORCO (HYDROCODONE- 6 tablets/day 12 tablets/day ACETAMINOPHEN) TAB 7.5-325 MG

NUCYNTA (TAPENTADOL HCL) 2 tablets/day 4 tablets/day TAB 50 MG

NUCYNTA (TAPENTADOL HCL) 1 tablet/day 3 tablets/day TAB 75 MG

NUCYNTA (TAPENTADOL HCL) 1 tablet/day 2 tablets/day TAB 100 MG

OPANA (OXYMORPHONE HCL) 3 tablets/day 6 tablets/day TAB 5 MG

OPANA (OXYMORPHONE HCL) 1 tablet/day 3 tablets/day TAB 10 MG

OXAYDO (OXYCODONE HCL) TAB 6 tablets/day 12 tablets/day ABUSE DETER 5 MG

OXAYDO (OXYCODONE HCL) TAB 4 tablets/day 8 tablets/day ABUSE DETER 7.5 MG

OXYCODONE HCL CAP 5 MG 6 capsules/day 12 capsules/day

OXYCODONE HCL CONC 100 1.6mL/day 3mL/day MG/5ML (20 MG/ML)

OXYCODONE HCL SOLN 5 32.6mL/day 60mL/day MG/5ML

OXYCODONE HCL TAB 10 MG 3 tablets/day 6 tablets/day

OXYCODONE HCL TAB 20 MG 1 tablet/day 3 tablets/day

OXYCODONE W/ 32.6mL/day 60mL/day ACETAMINOPHEN SOLN 5-325

Page 657 MG/5ML

OXYCODONE-ASPIRIN TAB 6 tablets/day 12 tablets/day 4.8355-325 MG

OXYCODONE-IBUPROFEN TAB 5- 6 tablets/day Requests over 49 MME exceed the 400 MG FDA max.

PENTAZOCINE W/ NALOXONE 2 tablets/day 4 tablets/day TAB 50-0.5 MG

PERCOCET (OXYCODONE W/ 12 tablets/day Requests over 49 MME exceed the ACETAMINOPHEN) TAB 2.5-325 FDA max. MG

PERCOCET (OXYCODONE W/ 6 tablets/day 12 tablets/day ACETAMINOPHEN) TAB 5-325 MG

PERCOCET (OXYCODONE W/ 4 tablets/day 8 tablets/day ACETAMINOPHEN) TAB 7.5-325 MG

PERCOCET (OXYCODONE W/ 3 tablets/day 6 tablets/day ACETAMINOPHEN) TAB 10-325 MG

PRIMLEV (OXYCODONE W/ 6 tablets/day 12 tablets/day ACETAMINOPHEN) TAB 5-300 MG

PRIMLEV (OXYCODONE W/ 4 tablets/day 8 tablets/day ACETAMINOPHEN) TAB 7.5-300 MG

PRIMLEV (OXYCODONE W/ 3 tablets/day 6 tablets/day ACETAMINOPHEN) TAB 10-300 MG

ROXYBOND TAB 15MG 2 tablets/day 4 tablets/day

ROXYBOND TAB 30MG 1 tablet/day 2 tablets/day

ROXICODONE (OXYCODONE 6 tablets/day 12 tablets/day HCL) TAB 5 MG

ROXICODONE (OXYCODONE 2 tablets/day 4 tablets/day HCL) TAB 15 MG

Page 658 ROXICODONE (OXYCODONE 1 tablet/day 2 tablets/day HCL) TAB 30 MG

SYNAPRYN (TRAMADOL ) ORAL 40mL/day Requests over 49 MME exceed the SUSP 10MG/ML CPDKT FDA max.

TYLENOL/COD TAB #3 10 tablets/day 20 tablets/day. Plan's supply limit from (ACETAMINOPHEN W/ CODEINE) the master supply limit grid is more TAB 300-30 MG restrictive.

TYLENOL/COD TAB #4 5 tablets/day 10 tablets/day (ACETAMINOPHEN W/ CODEINE) TAB 300-60 MG

ULTRAM (TRAMADOL HCL) TAB 8 tablets/day Requests over 49 MME exceed the 50MG FDA max.

ULTRACET (TRAMADOL- 10 tablets/day Requests over 49 MME exceed the ACETAMINOPHEN) TAB 37.5-325 FDA max.

XODOL (HYDROCODONE- 9 tablets/day 18 tablets/day. Plan's supply limit from ACETAMINOPHEN) TAB 5-300 MG the master supply limit grid is more restrictive.

XODOL (HYDROCODONE- 6 tablets/day 12 tablets/day ACETAMINOPHEN) TAB 7.5-300 MG

3 . References

1. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. JAMA. Published online March 15, 2016.

4 . Revision History

Date Notes

5/19/2021 Annual review. Administrative change for formatting.

Page 659 Silenor (doxepin)

Prior Authorization Guideline

GL-6092 Silenor (doxepin)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

CPS Approval Date: 12/7/2010

1 . Indications Drug Name: Silenor (doxepin) Insomnia [1] Is indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. The clinical trials performed in support of efficacy were up to 3 months in duration.

2 . Criteria

Product Name: Silenor (doxepin)

Page 660 Guideline Type Non Formulary

Approval Criteria

1 - History of failure, contraindication, or intolerance to both of the following:

• Ambien (zolpidem) • Lunesta (eszopiclone)

3 . References

1. Silenor Prescribing Information. Somaxon Pharmaceuticals, Inc., March 2010.

Page 661 Slynd (drospirenone) - PA/Med Nec

Prior Authorization Guideline

GL-87098 Slynd (drospirenone) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 1/15/2020 P&T Revision Date: 07/15/2020 ; 4/21/2021

1 . Indications Drug Name: Slynd (drospirenone) Pregnancy Prevention Oral contraceptives are available as either combination estrogen/progesterone-containing contraceptives or as progesterone-only contraceptives. Progesterone-only contraceptives should be used when estrogen-containing contraceptives are contraindicated. Slynd (drospirenone) is a progesterone-only contraceptive indicated for use by females of reproductive potential to prevent pregnancy.

2 . Criteria

Product Name: Slynd [a] Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 662 Guideline Type Prior Authorization

Approval Criteria

1 - Used for the prevention of pregnancy

AND

2 - Use of estrogen-containing contraceptives is contraindicated (e.g., breast feeding, comorbidities/health conditions)

AND

3 - History of failure, contraindication, or intolerance to norethindrone (generic Ortho Micronor)

AND

4 - Prescriber attests the benefits of drospirenone-containing, progestin-only contraceptives outweigh the potential risk of venous thromboembolism Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Slynd [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Slynd therapy

AND

Page 663

2 - Use of estrogen-containing contraceptives is contraindicated (e.g., breast feeding, comorbidities/health conditions) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

Oral contraceptives are available as either combination estrogen/progesterone-containing contraceptives or as progesterone-only contraceptives. Progesterone-only contraceptives should be used when estrogen-containing contraceptives are contraindicated. Slynd (drospirenone) is a progesterone-only contraceptive indicated for use by females of reproductive potential to prevent pregnancy.

Additional Clinical Programs: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Slynd [package insert]. Florham Park, NJ: Exeltis USA, Inc; May 2019. 2. Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep 2016;65(No. RR-4):1–66. DOI: http://dx.doi.org/10.15585/mmwr.rr6504a1

5 . Revision History

Date Notes

5/18/2021 Simplified contraindication language and added documentation of cont raindication.

Page 664

Page 665 Solaraze (diclofenac 3% gel)

Prior Authorization Guideline

GL-71188 Solaraze (diclofenac 3% gel)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 8/19/2015 P&T Revision Date: 7/15/2020

1 . Indications Drug Name: Solaraze (diclofenac 3% gel) Actinic Keratosis Indicated for the topical treatment of actinic keratosis (AK).

2 . Criteria

Product Name: Solaraze* Approval Length 3 month(s) Guideline Type Notification

Approval Criteria

Page 666

1 - Diagnosis of actinic keratosis Notes *Applies to brand and generic Solaraze

3 . Background

Benefit/Coverage/Program Information

Background:

The recommended duration of therapy is from 60 to 90 days.

4 . References

1. Solaraze prescribing information. PharmDerm. Melville, NY. May, 2016.

5 . Revision History

Date Notes

8/7/2020 Annual review. No changes.

Page 667 Solosec (secnidazole) - Step Therapy

Prior Authorization Guideline

GL-84788 Solosec (secnidazole) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 4/18/2018 P&T Revision Date: 03/01/2020 ; 3/17/2021

1 . Indications Drug Name: Solosec (secnidazole) bacterial vaginosis Indicated for the treatment of bacterial vaginosis.

2 . Criteria

Product Name: Solosec [a] Approval Length 1 month(s) Guideline Type Step Therapy

Approval Criteria

Page 668

1 - History of failure, contraindication or intolerance to one of the following:

• clindamycin capsules (generic Cleocin) • clindamycin vaginal cream (generic Cleocin, Clindesse) • clindamycin vaginal suppository (Cleocin) • metronidazole tablets (generic Flagyl) • metronidazole vaginal gel (Metrogel-Vaginal) • tinidazole tablets (generic Tindamax)

3 . Background

Benefit/Coverage/Program Information

Background:

Solosec (secnidazole) is indicated for the treatment of bacterial vaginosis. Solosec is available as a two gram oral granule and should be taken as a single dose.

Step therapy programs are intended to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try an alternative antibacterial agent before providing coverage for Solosec.

Additional Clinical Rules

4 . References

1. Solosec [package insert]. Baltimore, MD: Lupin Pharmaceuticals, Inc.; January 2021. 2. 2015 Sexually Transmitted Diseases Treatment Guidelines. Bacterial Vaginosis. Centers for Disease Control and Prevention. June 2015. https://www.cdc.gov/std/tg2015/bv.htm. Accessed January 2021.

Page 669

5 . Revision History

Date Notes

4/30/2021 Annual review. Updated references.

Page 670 Sprix (ketorolac) - Step Therapy

Prior Authorization Guideline

GL-90389 Sprix (ketorolac) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 4/15/2020 P&T Revision Date: 6/16/2021

1 . Indications Drug Name: Sprix (ketorolac) Moderate to moderately severe pain Indicated in adult patients for the short-term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level.

2 . Criteria

Product Name: Sprix (ketorolac) [a] Diagnosis moderate to moderately severe pain Approval Length 12 month(s) Guideline Type Step Therapy

Page 671

Approval Criteria

1 - History of failure, contraindication, or intolerance to three of the following oral products:

• diclofenac • flurbiprofen • ibuprofen (prescription strength) • naproxen (prescription strength)

2 - Member is unable to swallow oral products due to dysphagia, esophagitis, mucositis, or uncontrollable nausea/vomiting Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Programs:

4 . References

1. Sprix [package insert]. Wayne, PA: Zyla Life Sciences US Inc.; March 2020

5 . Revision History

Date Notes

Page 672 7/26/2021 Annual review with no changes.

Page 673 Statins - NonFormulary and Step Therapy

Prior Authorization Guideline

GL-76604 Statins - NonFormulary and Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 1/1/2021 P&T Approval Date: 4/17/2019 P&T Revision Date: 10/16/2019 ; 10/21/2020

1 . Criteria

Product Name: [Lescol XL (fluvastatin extended-release, brand only)*, Livalo (pitavastatin calcium)*, or Zypitamag (pitavastatin magnesium)*] [a] Approval Length 12 Months Guideline Type NonFormulary and Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to three of the following:

• atorvastatin (generic Lipitor) • fluvastatin (generic Lescol)

Page 674 • lovastatin (generic Mevacor) • pravastatin (generic Pravachol) • rosuvastatin (generic Crestor) • simvastatin (generic Zocor)

Notes *Brand Lescol XL, Livalo, and Zypitamag may be excluded from covera ge depending on benefit design. [a] State mandates may apply. Any fe deral regulatory requirements and the member specific benefit plan cov erage may also impact coverage criteria. Other policies and utilization management programs may apply.

2 . Background

Benefit/Coverage/Program Information

Background:

This program requires a member to try three alternative statin medications before providing coverage for Lescol XL, Livalo, or Zypitamag.

Additional Clinical Rules:

• Supply limits may apply • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

3 . References

1. Lescol XL [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corporation; December 2018. 2. Livalo [package insert]. Montgomery, AL: Kowa Pharmaceuticals America, Inc. May 2019. 3. Zypitamag [package insert]. Somerset, NJ: Medicure. August 2019. 4. Grundy et. al. 2018 HA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):3168- 3209.

Page 675 4 . Revision History

Date Notes

11/4/2020 Annual review. Updated references.

Page 676 Sublingual Immunotherapy (SLIT) - PA/Med Nec

Prior Authorization Guideline

GL-84766 Sublingual Immunotherapy (SLIT) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 5/21/2014 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Indications Drug Name: Sublingual Immunotherapy (SLIT) Medications Allergic rhinitis Indicated for patients who have symptoms of allergic rhinitis with natural exposure to allergens and who demonstrate specific IgE antibodies to the relevant allergen.

Drug Name: Grastek, Oralair Allergic rhinitis Indicated for patients with grass pollen-induced allergic rhinitis.

Drug Name: Odactra Allergic rhinitis Indicated for house dust mite (HDM)-induced allergic rhinitis.

Drug Name: Ragwitek Allergic rhinitis Indicated for ragweed pollen-induced allergic rhinitis.

Page 677

2 . Criteria

Product Name: Grastek [a] Diagnosis grass pollen-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe grass pollen-induced allergic rhinitis

AND

2 - Diagnosis confirmed by one of the following:

2.1 Positive skin test to Timothy grass or cross-reactive grass pollens (e.g., Sweet Vernal, Orchard/Cocksfoot, Perennial Rye, Kentucky blue/June grass, Meadow Fescue, or Redtop)

2.2 in vitro testing for pollen-specific IgE antibodies for Timothy grass or cross-reactive grass pollens (e.g., Sweet Vernal, Orchard/Cocksfoot, Perennial Rye, Kentucky blue/June grass, Meadow Fescue, or Redtop)

AND

3 - Treatment is started or will be started at least 12 weeks before the beginning of the grass pollen season

AND

4 - History of failure, contraindication, or intolerance to two of the following:

Page 678 • oral antihistamine [e.g. cetirizine (Zyrtec)] • intranasal antihistamine [e.g. azelastine (Astelin)] • intranasal corticosteroid [e.g. fluticasone (Flonase)] • leukotriene inhibitor [e.g. montelukast (Singulair)]

AND

5 - Not received in combination with similar cross-reactive grass pollen immunotherapy (e.g., Oralair)

AND

6 - Patient does not have unstable and/or uncontrolled asthma

AND

7 - Prescribed by or in consultation with a specialist in allergy and immunology Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Grastek [a] Diagnosis grass pollen-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Grastek therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 679 Product Name: Oralair [a] Diagnosis grass pollen-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe grass pollen-induced allergic rhinitis

AND

2 - Diagnosis confirmed by one of the following:

2.1 Positive skin test to any of the five grass species contained in Oralair [(i.e., Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue grass mixed pollens) or cross-reactive grass pollens (e.g., Cocksfoot, Meadow Fescue, or Redtop)]

2.2 in vitro testing for pollen-specific IgE antibodies for any of the five grass species contained in Oralair [(i.e., Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue grass mixed pollens) or cross-reactive grass pollens (e.g., Cocksfoot, Meadow Fescue, or Redtop)]

AND

3 - Treatment is started or will be started at least 4 months before the beginning of the grass pollen season

AND

4 - History of failure, contraindication, or intolerance to two of the following:

• oral antihistamine [e.g. cetirizine (Zyrtec)] • intranasal antihistamine [e.g. azelastine (Astelin)] • intranasal corticosteroid [e.g. fluticasone (Flonase)]

Page 680 • leukotriene inhibitor [e.g. montelukast (Singulair)]

AND

5 - Not received in combination with similar cross-reactive grass pollen immunotherapy (e.g., Grastek)

AND

6 - Patient does not have unstable and/or uncontrolled asthma

AND

Product Name: Oralair [a] Diagnosis grass pollen-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Oralair therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Ragwitek [a] Diagnosis ragweed pollen-induced allergic rhinitis

Page 681 Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of moderate to severe short ragweed pollen-induced allergic rhinitis

AND

2 - Diagnosis confirmed by one of the following:

• Positive skin test to short ragweed pollen • in vitro testing for pollen-specific IgE antibodies for short ragweed pollen

AND

3 - Treatment is started or will be started at least 12 weeks before the beginning of the short ragweed pollen season

AND

4 - History of failure, contraindication, or intolerance to two of the following:

• oral antihistamine [e.g. cetirizine (Zyrtec)] • intranasal antihistamine [e.g. azelastine (Astelin)] • intranasal corticosteroid [e.g. fluticasone (Flonase)] • leukotriene inhibitor [e.g. montelukast (Singulair)]

AND

5 - Patient does not have unstable and/or uncontrolled asthma

AND

6 - Prescribed by or in consultation with a specialist in allergy and immunology

Page 682 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Ragwitek [a] Diagnosis ragweed pollen-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Ragwitek therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Odactra [a] Diagnosis house dust mite (HDM)-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of house dust mite (HDM)-induced allergic rhinitis

AND

2 - Diagnosis confirmed by one of the following:

• Positive skin test to licensed house dust mite allergen extracts • in vitro testing for IgE antibodies to Dermatophagoides farinae or Dermatophagoides pteronyssinus house dust mites

Page 683

AND

3 - History of failure, contraindication, or intolerance to two of the following:

AND

4 - Patient does not have unstable and/or uncontrolled asthma

AND

5 - Prescribed by or in consultation with a specialist in allergy and immunology Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Odactra [a] Diagnosis house dust mite (HDM)-induced allergic rhinitis Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Odactra therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Page 684 3 . Background

Benefit/Coverage/Program Information

Background:

The sublingual immunotherapy (SLIT) medications are indicated for patients who have symptoms of allergic rhinitis with natural exposure to allergens and who demonstrate specific IgE antibodies to the relevant allergen. Grastek (Timothy grass pollen allergen extract) and Oralair (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass Mixed Pollens allergen extract) are indicated for patients with grass pollen-induced allergic rhinitis, Ragwitek (short ragweed pollen allergen extract) is indicated for ragweed pollen-induced allergic rhinitis and Odactra (Dermatophagoides farinae/Dermatophagoides pteronyssinus allergen extract), is indicated for house dust mite (HDM)-induced allergic rhinitis.

Candidates for allergen immunotherapy are patients whose symptoms are not adequately controlled by medications, and avoidance measures have been ineffective. In addition, patients experiencing unacceptable adverse effects of medications or who wish to reduce the long term use of medications may also be candidates for immunotherapy.

Additional Clinical Rules: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class • Supply limits and/or Notification may be in place.

4 . References

1. Grastek® [package insert]. Blagrove Swindon Wiltshire, UK: Catalent Pharma Solutions Limited;; August 2020 2. Oralair® [package insert]. Lenoir, NC: Greer Laboratories, Inc.: . January 2021. 3. Ragwitek® [package insert]. Blagrove Swindon, Wiltshire, UK: Catalent Pharma Solutions Limited;. August 2020. 4. Ocactra® [package insert]. Blagrove,Swindon, Wiltshire, UK: Catalent Pharma Solutions Limited: August 2019. 5. Cox, L, Nelson, H, Lockey, R, et al. Allergen immunotherapy: A practice parameter third update. American Academy of Allergy, Asthma & Immunology. December 2010. 6. Treatment of seasonal allergic rhinitis: An evidence-based focused 2017 guideline update. Dykewicz MS, Wallace DV, Baroody F, et.al. Ann Allergy Asthma Immunol. 2017 Dec;119(6):489-511.e41 7. Sublingual immunotherapy: A focused allergen immunotherapy practice parameter update. Greenhawt M, Oppenheimer J, Nelson M, et.al. Ann Allergy Asthma Immunol. 2017 Mar;118(3):276-82.e2.

Page 685

5 . Revision History

Date Notes

4/30/2021 Annual review. Updated references.

Page 686 Sunosi (solriamfetol)

Prior Authorization Guideline

GL-71341 Sunosi (solriamfetol)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 7/17/2019 P&T Revision Date: 7/15/2020

1 . Indications Drug Name: Sunosi (solriamfetol) Narcolepsy , Obstructive Sleep Apnea Indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA).

2 . Criteria

Product Name: Sunosi Diagnosis Narcolepsy Approval Length 6 month(s) Therapy Stage Initial Authorization

Page 687 Guideline Type Notification

Approval Criteria

1 - Diagnosis of narcolepsy as confirmed by sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible) [2]

AND

2 - Symptoms of excessive daytime sleepiness (including but not limited to daily periods of irrepressible need to sleep or daytime lapses into sleep) are present.

Product Name: Sunosi Diagnosis Narcolepsy Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Reduction in symptoms of excessive daytime sleepiness associated with Sunosi therapy

Product Name: Sunosi Diagnosis Obstructive Sleep Apnea Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Notification

Approval Criteria

1 - Diagnosis of obstructive sleep apnea as confirmed by sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible)

AND

Page 688

2 - Both of the following:

2.1 Standard treatments for the underlying airway obstruction (e.g., continuous positive airway pressure [CPAP], bi-level positive airway pressure [BiPAP]) have been used for one month or longer

AND

2.2 Patient is fully compliant with ongoing treatment(s) for the underlying airway obstruction

Product Name: Sunosi Diagnosis Obstructive Sleep Apnea Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Reduction in symptoms of excessive daytime sleepiness associated with Sunosi therapy

AND

2 - Patient continues to be fully compliant with ongoing treatment(s) for the underlying airway obstruction (e.g., CPAP, BiPAP)

3 . Background

Benefit/Coverage/Program Information

Background:

Sunosi is a dopamine and norepinephrine reuptake inhibitor (DNRI) indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA).1

Page 689

Limitations of Use: Sunosi is not indicated to treat the underlying airway obstruction in OSA. Ensure that the underlying airway obstruction is treated (e.g., with continuous positive airway pressure [CPAP]) for at least one month prior to initiating Sunosi for excessive daytime sleepiness. Modalities to treat the underlying airway obstruction should be continued during treatment with Sunosi. Sunosi is not a substitute for these modalities.

4 . References

1. Sunosi [package insert]. Palo Alto, CA: Jazz Pharmaceuticals, Inc; June 2019. 2. American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.

5 . Revision History

Date Notes

8/13/2020 Annual review. Updated references.

Page 690 Symlin (pramlintide acetate injection)

Prior Authorization Guideline

GL-16468 Symlin (pramlintide acetate injection)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 6/7/2005; P&T Revision Date: 2/25/2016. **Effective 7/1/2016** According to Texas State Law, all diabetic medications used for the treatment of diabetes shall be covered.

1 . Indications Drug Name: Symlin (pramlintide acetate) Type 1 Diabetes Mellitus Indicated for type 1 diabetes, as an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy.

Type 2 Diabetes Mellitus Indicated for type 2 diabetes, as an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy, with or without a concurrent sulfonylurea agent and/or metformin.

Page 691

2 . Criteria

Product Name: Symlin Approval Length 12 Month Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

• Type 1 diabetes • Type 2 diabetes

AND

2 - Age greater than or equal to 18 years [A]

AND

3 - Concurrent use of insulin therapy

AND

4 - Not used in patients with gastroparesis Notes Symlin is contraindicated in patients with hypoglycemia unawareness a nd known diagnosis of gastroparesis.

3 . Endnotes

A. Symlin has not been evaluated in the pediatric population. Safety and effectiveness of Symlin in pediatric patients have not been established. [1]

Page 692 4 . References

1. Symlin Prescribing Information. Amylin Pharmaceuticals, Inc., February 2015. 2. AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19 (No. 2) 3. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient centered approach. Diabetes Care. 2012, 19 April 2012 [Epub ahead of print] 4. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2013; 36 (suppl 1): S11-S66.

Page 693 Tasmar (tolcapone) - PA/Med Nec

Prior Authorization Guideline

GL-85964 Tasmar (tolcapone) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 3/17/2021

P&T Revision Date:

1 . Indications Drug Name: Tasmar (tolcapone) Parkinson's Disease Indicated as an adjunct to levodopa/carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson’s Disease. Due to the of the risk of liver failure, Tasmar (tolcapone) should be used in patients with Parkinson’s disease treated with levodopa/carbidopa who are experiencing symptom fluctuations and are not responding to or are not appropriate candidates for other adjunctive therapies. A patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment should be withdrawn from Tasmar therapy due to the risk of liver failure.

2 . Criteria

Product Name: Tasmar [a]

Page 694 Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Parkinson’s disease

AND

2 - Patient is currently on a stable dose of a carbidopa/levodopa-containing medication and will continue receiving treatment with a carbidopa/levodopa-containing medication while on therapy

AND

3 - History of failure, contraindication, or intolerance to all of the following anti-Parkinson’s disease adjunctive pharmacotherapy classes (trial must be from all of the different classes):

• Dopamine agonists (e.g., pramipexole, ropinirole) • Catechol-O-methyl transferase (COMT) inhibitors (e.g., entacapone) • Monoamine oxidase (MAO) B inhibitors (e.g., rasagiline, selegiline)

AND

4 - Patient has received baseline liver function tests to rule out the presence of underlying liver disease

AND

5 - Prescribed by or in consultation with a neurologist or specialist in the treatment of Parkinson’s disease

AND

6 - Prescriber attests they have had complete discussion with the patient about the risks and benefits of Tasmar use, including the risk of liver failure

Page 695 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Tasmar [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Tasmar therapy

AND

2 - Patient will continue to receive treatment with a carbidopa/levodopa-containing medication

AND

3 - Patient has received periodic evaluation of liver function tests to rule out liver failure associated with Tasmar use Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background:

Tasmar (tolcapone) is catechol-O-methyltransferase (COMT) inhibitor indicated as an adjunct to levodopa/carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson’s Disease. Due to the of the risk of liver failure, Tasmar (tolcapone) should be used in patients

Page 696 with Parkinson’s disease treated with levodopa/carbidopa who are experiencing symptom fluctuations and are not responding to or are not appropriate candidates for other adjunctive therapies. A patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment should be withdrawn from Tasmar therapy due to the risk of liver failure.

Additional Clinical Rules:

4 . References

1. Tasmar [package insert]. Bridgewater, NJ: Bausch Health US, LLC; October 2020. 2. Fox, SH, Katzenschlager, R, Lim S, et. al. International Parkinson and Movement Disorder Society Evidence-Based Medicine Review: Update on Treatments for the Motor Symptoms of Parkinson’s Disease. Movement Disorders. 2018.

5 . Revision History

Date Notes

4/20/2021 New Program.

Page 697 Temodar (temozolomide)

Prior Authorization Guideline

GL-45575 Temodar (temozolomide)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 8/1/2009; P&T Revision Date: 9/27/2017, 9/19/2018. **Effective Date: 12/1/2018**

1 . Indications Drug Name: Temodar (temozolomide) Glioblastoma multiforme Indicated for treatment in patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.[1]

Refractory anaplastic astrocytoma Indicated for treatment of adult patients with refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

Page 698 2 . Criteria

Product Name: Brand Temodar, Generic temozolomide Diagnosis Patients less than 19 years of age Approval Length 12 Month Guideline Type Prior Authorization

Approval Criteria

1 - Patient is less than 19 years of age

Product Name: Brand Temodar, Generic temozolomide Diagnosis Central Nervous Systems (CNS) Tumor Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

• Intracranial and Spinal Ependymoma (Excluding Subependymoma) • Low-Grade Infiltrative Supratentorial Astrocytoma/Oligodendroglioma • Medulloblastoma • Anaplastic Gliomas • Glioblastoma • Metastatic lesions of the CNS • Primary CNS lymphoma

Product Name: Brand Temodar, Generic temozolomide Diagnosis Central Nervous Systems (CNS) Tumor Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 699

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Melanoma/Uveal Melanoma Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of melanoma or uveal melanoma

Product Name: Brand Temodar, Generic temozolomide Diagnosis Melanoma/Uveal Melanoma Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Neuroendocrine and Adrenal Tumors Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

Page 700 1 - Diagnosis of one of the following types of neuroendocrine tumors

• Bronchopulmonary disease • GI tract, lung, or thymus • Pancreas • Pheochromocytoma/paraganglioma

Product Name: Brand Temodar, Generic temozolomide Diagnosis Neuroendocrine and Adrenal Tumors Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Non-Hodgkin Lymphoma (NHL) Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following diagnoses:

• Mycosis fungoides (MF) • Sezary syndrome (SS)

Product Name: Brand Temodar, Generic temozolomide Diagnosis Non-Hodgkin Lymphoma (NHL) Approval Length 12 Month Therapy Stage Reauthorization

Page 701 Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Soft Tissue Sarcoma Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Diagnosis of angiosarcoma

1.2 Diagnosis of unresectable or progressive retroperitoneal/ intra-abdominal soft tissue sarcoma

1.3 Diagnosis of rhabdomyosarcoma

1.4 Both of the following:

1.4.1 Diagnosis of soft tissue sarcoma of the extremity/ superficial trunk, Head/Neck

AND

Page 702

1.4.2 One of the following:

• Disease synchronous stage IV • Disease has disseminated metastases

1.5 Both of the following:

1.5.1 Diagnosis of solitary fibrous tumor/ hemangiopericytoma

AND

1.5.2 Used in combination with Avastin (bevacizumab)

Product Name: Brand Temodar, Generic temozolomide Diagnosis Soft Tissue Sarcoma Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Bone Cancer Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of one of the following:

Page 703 • Ewing's sarcoma family of tumors • Mesenchymal Chondrosarcoma

AND

2 - One of the following:

• Disease has relapsed • Disease is progressive following primary treatment • Used as second-line therapy for metastatic disease

AND

3 - Used in combination with Campostar (irinotecan)

Product Name: Brand Temodar, Generic temozolomide Diagnosis Bone Cancer Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Uterine Sarcoma Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of uterine sarcoma

Page 704

Product Name: Brand Temodar, Generic temozolomide Diagnosis Uterine Sarcoma Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

Product Name: Brand Temodar, Generic temozolomide Diagnosis Small Cell Lung Cancer (SCLC) Approval Length 12 Month Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of small cell lung cancer (SCLC)

AND

2 - One of the following:

• Relapse within 6 months following complete or partial response or stable disease with initial treatment • Primary progressive disease

Product Name: Brand Temodar, Generic temozolomide Diagnosis Small Cell Lung Cancer (SCLC) Approval Length 12 Month Therapy Stage Reauthorization

Page 705 Guideline Type Prior Authorization

Approval Criteria

1 - Patient does not show evidence of progressive disease while on Temodar therapy

3 . Background

Benefit/Coverage/Program Information

Background:

Temodar (temozolomide) is an alkylating drug indicated for treatment in patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.[1] It is also indicated for treatment of adult patients with refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine. The National Comprehensive Cancer Network (NCCN) also recommends Temodar for the treatment of CNS cancers - primary astrocytoma/oligodendroglioma or anaplastic glioma central nervous system tumors, ependymoma, metastatic central nervous system lesions, primary central nervous system lymphoma, medulloblastoma; melanoma and uveal melanoma; pancreatic neuroendocrine disorders; NHL – mycosis fungoides (MF) and Sézary syndrome (SS); soft tissue sarcoma (STS), Ewing’s sarcoma; mesenchymal chondrosarcoma; lung neuroendocrine tumors; pheochromocytoma/paraganglioma neuroendocrine and adrenal tumors; uterine sarcoma; or small cell lung cancer (SCLC).[2]

Coverage Information

Members will be required to meet the criteria below for coverage. For members under the age of 19 years, the prescription will automatically process without a coverage review.

Some states mandate benefit coverage for off-label use of medications for some diagnoses or under some circumstances. Some states also mandate usage of other Compendium references. Where such mandates appy, they supersede language in the benefit document or in the notification criteria.

Additional Clinical Rules:

Supply limits may be in place.

4 . References

Page 706 1. Temodar [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.,.; October 2017. 2. The NCCN Drugs and Biologics Compendium (NCCN Compendium™). Available at http://www.nccn.org/professionals/drug_compendium/content/contents.asp. Accessed July 30, 2018.

Page 707 Topical Androgens

Prior Authorization Guideline

GL-49285 Topical Androgens

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 2/18/2014; P&T Revision Date: 2/15/2019. Guideline Effective Date: 5/1/2019.

1 . Criteria

Product Name: Preferred products (Androderm, Androgel 1.62%, generic testosterone pump 1%) Diagnosis Hypogonadism Approval Length 6 months for patients new to any topical testosterone therapy; 12 months for patients continuing testosterone therapy Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 708

Approval Criteria

1 - One of the following:

1.1 Patient has a history of one of the following:

• Bilateral orchiectomy • Panhypopituitarism • A genetic disorder known to cause hypogonadism (e.g., congenital anorchia, Klinefelter’s syndrome)

1.2 All of the following:

1.2.1 One of the following:

1.2.1.1 Two pre-treatment serum total testosterone levels less than 300 ng/dL (less than 10.4 nmol/L) or less than the reference range for the lab, taken at separate times (This may require treatment to be temporarily held. Document lab value and date for both levels)

1.2.1.2 Both of the following:

1.2.1.2.1 Patient has a condition that may cause altered sex-hormone binding globulin (SHBG) (e.g., thyroid disorder, HIV disease, liver disorder, diabetes, obesity)

AND

1.2.1.2.2 One pre-treatment calculated free or bioavailable testosterone level less than 50 pg/mL (less than 5 ng/dL or less than 0.17 nmol/L) or less than the reference range for the lab (This may require treatment to be temporarily held. Document lab value and date)

AND

1.2.2 Patient is not taking any of the following:

• One of the following growth hormones, unless diagnosed with panhypopituitarism:

Page 709 Genotropin, Humatrope, Norditropin FlexPro, Nutropin AQ, Omnitrope, Saizen • Aromatase inhibitor (eg, Arimidex [anastrozole], Femara [letrozole], Aromasin [exemestane])

AND

1.2.3 Patient was male at birth

AND

1.2.4 Diagnosis of hypogonadism

AND

1.2.5 One of the following:

• Significant reduction in weight (less than 90% ideal body weight) (eg, AIDS wasting syndrome) • Osteopenia • Osteoporosis • Decreased bone density • Decreased libido • Organic cause of testosterone deficiency (eg, injury, tumor, infection, or genetic defects)

Product Name: Non-preferred products (brand Androgel gel and pump 1%, Axiron, Fortesta (brand and generic), Natesto, brand Testim, generic testosterone gel 1%, generic testosterone gel 2%, Striant, Brand Vogelxo gel and pump) Diagnosis Hypogonadism Approval Length 6 months for patients new to any topical testosterone therapy; 12 months for patients continuing testosterone therapy Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

Page 710 1.1 Patient has a history of one of the following:

• Bilateral orchiectomy • Panhypopituitarism • A genetic disorder known to cause hypogonadism (e.g., congenital anorchia, Klinefelter’s syndrome)

1.2 All of the following:

1.2.1 One of the following:

1.2.1.2 Both of the following:

1.2.1.2.1 Patient has a condition that may cause altered sex-hormone binding globulin (SHBG) (e.g., thyroid disorder, HIV disease, liver disorder, diabetes, obesity)

AND

1.2.2 Patient is not taking any of the following:

• One of the following growth hormones, unless diagnosed with panhypopituitarism: Genotropin, Humatrope, Norditropin FlexPro, Nutropin AQ, Omnitrope, Saizen • Aromatase inhibitor (eg, Arimidex [anastrozole], Femara [letrozole], Aromasin [exemestane])

Page 711 AND

1.2.3 Patient was male at birth

AND

1.2.4 Diagnosis of hypogonadism

AND

1.2.5 One of the following:

AND

2 - History of failure or intolerance to Androgel 1.62%

Product Name: Preferred products (Androderm, Androgel 1.62%, generic testosterone pump 1%) Diagnosis Gender Dysphoria+ Approval Length 6 months for patients new to any topical testosterone therapy; 12 months for patients continuing testosterone therapy Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Using hormones to change physical characteristics

Page 712 AND

2 - The covered person must be diagnosed with gender dysphoria, as defined by the current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM)

AND

3 - Patient is not taking any of the following:

Product Name: Non-preferred products (brand Androgel gel and pump 1%, Axiron, Fortesta (brand and generic), Natesto, brand Testim, generic testosterone gel 1%, generic testosterone gel 2%, Striant, Brand Vogelxo gel and pump) Diagnosis Gender Dysphoria+ Approval Length 6 months for patients new to any topical testosterone therapy; 12 months for patients continuing testosterone therapy Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Using hormones to change physical characteristics

AND

2 - The covered person must be diagnosed with gender dysphoria, as defined by the current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM)

AND

3 - Patient is not taking any of the following:

Page 713 • One of the following growth hormones, unless diagnosed with panhypopituitarism: Genotropin, Humatrope, Norditropin FlexPro, Nutropin AQ, Omnitrope, Saizen • Aromatase inhibitor (eg, Arimidex [anastrozole], Femara [letrozole], Aromasin [exemestane])

AND

4 - History of failure or intolerance to Androgel 1.62%

Product Name: Preferred and Non-preferred products Diagnosis Non-Gender Dysphoria and Gender Dysphoria Approval Length 12 Month Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Patient has a history of one of the following:

• Bilateral orchiectomy • Panhypopituitarism • A genetic disorder known to cause hypogonadism (eg, congenital anorchia, Klinefelter’s syndrome)

1.2 Reauthorization will be approved based on both of the following:

1.2.1 One of the following:

1.2.1.1 Follow-up total serum testosterone level drawn within the past 6 months for patients new to testosterone therapy (i.e. on therapy for less than one year), or 12 months for patients continuing testosterone therapy (i.e. on therapy for one year or longer), is within or below the normal male limits of the reporting lab (document value and date)

Page 714 OR

1.2.1.2 Follow-up total serum testosterone level drawn within the past 6 months for patients new to testosterone therapy (i.e. on therapy for less than one year), or 12 months for patients continuing testosterone therapy (i.e. on therapy for one year or longer), is outside of upper male limits of normal for the reporting lab and the dose is adjusted (document value and date)

1.2.1.3 Both of the following:

1.2.1.3.1 Patient has a condition that may cause altered sex-hormone binding globulin (SHBG) (e.g., thyroid disorder, HIV disease, liver disorder, diabetes, obesity)

AND

1.2.1.3.2 One of the following:

1.2.1.3.2.1 Follow-up calculated free or bioavailable testosterone level drawn within the past 6 months for patients new to testosterone therapy (i.e. on therapy for less than one year), or 12 months for patients continuing testosterone therapy (i.e. on therapy for one year or longer), is within or below the normal male limits of the reporting lab (document lab value and date)

1.2.1.3.2.2 Follow-up calculated free or bioavailable testosterone level drawn within the past 6 months for patients new to testosterone therapy (i.e. on therapy for less than one year), or 12 months for patients continuing testosterone therapy (i.e. on therapy for one year or longer), is outside of upper male limits of normal for the reporting lab and the dose is adjusted (document value and date)

AND

1.2.2 Patient is not taking any of the following:

• One of the following growth hormones, unless diagnosed with panhypopituitarism:

Page 715 Genotropin, Humatrope, Norditropin FlexPro, Nutropin AQ, Omnitrope, Saizen • Aromatase inhibitor (eg, Arimidex [anastrozole], Femara [letrozole], Aromasin [exemestane])

2 . Background

Benefit/Coverage/Program Information

Background:

Topical testosterone products are approved by the Food and Drug Administration (FDA) for testosterone replacement therapy in males with primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired). Primary hypogonadism originates from a deficiency or disorder in the testicles. Secondary hypogonadism indicates a problem in the hypothalamus or the pituitary gland. Testosterone use has been strongly linked to improvements in muscle mass, bone density, and libido.

The purpose of this program is to provide coverage for androgens and anabolic steroid therapy for the treatment of conditions for which they have shown to be effective and are within the scope of the plan’s pharmacy benefit. Coverage for the enhancement of athletic performance or body building will not be provided.

Additional Clinical Rules:

• Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place. • +Coverage for patient population may be dependent upon benefit design

3 . References

1. AACE Hypogonadism Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients - 2002 Update. Endocr Pract. 2002; 8(No. 6): 439- 456.

Page 716 2. The World Professional Association for Transgender Health (WPATH), Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, 7th Version. 3. Cook, David M, et al. "American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update: executive summary of recommendations." Endocrine practice 15.6 (2009):580-586. 4. Gibney, James, et al. "Growth hormone and testosterone interact positively to enhance protein and energy metabolism in hypopituitary men." American journal of physiology: endocrinology and metabolism 289.2 (2005):E266-E271 5. Bhasin, S, et al. "Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels." JAMA. 2000. 283.(6) 763-770. 6. Isidori, Andrea M, et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clinical endocrinology. 2005 63(4):381-394. 7. Kenny, A M, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. The journals of gerontology. 2001. 56(5) M266- M272. 8. Tracz, Michal J, et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. The Journal of clinical endocrinology and metabolism. 2006. 91(6):2011-2016. 9. Bolona, Enrique R, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clinic proceedings.2007. 82(1):20-28. 10. Androderm (testosterone) transdermal system. Prescribing information. Parsippany, NJ: Watson Laboratories, Inc., July 2015. 11. Androgel (testosterone) 1.62% gel. Prescribing information. Abbvie Inc. Chicago, IL. May 2015. 12. Androgel (testosterone) 1% gel. Prescribing information. Abbvie Inc. Chicago, IL. October 2016. 13. Axiron (testosterone) topical solution. Prescribing Information. Indianapolis, IN: Lilly USA, LLC. October 2016. 14. Fortesta (testosterone) 2% gel. Prescribing Information. Malvern, PA: Endo Pharmaceuticals. October 2016. 15. Testim (testosterone) 1% gel. Prescribing information. Malvern, PA: Endo Pharmaceuticals, Inc., October 2016. 16. Striant (testosterone) buccal system. Prescribing information. Endo Pharmaceuticals. Malvern, PA. October 2016. 17. Natesto (testosterone) nasal gel. Prescribing information. Endo Pharmaceuticals. Malvern, PA. May 2015. 18. Vogelxo (testosterone) gel. Prescribing information. Maple Grove, MN: Upsher-Smith Laboratories, September 2016. 19. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender- Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2017; 102:3869. 20. The Endocrine Society. Testosterone therapy in Adult Men with Androgen Deficiency Syndromes. J Clin Endocrinol Metab, May 2018, 103(5):1–30. 21. Mulhall JP, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. American Urological Association Education and Research, Inc 2018.

Page 717 Topical Antifungals - PA/Med Nec

Prior Authorization Guideline

GL-66162 Topical Antifungals - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2020 P&T Approval Date: 11/19/2014 P&T Revision Date: 4/15/2020

1 . Indications Drug Name: Jublia (efinaconazole) and Kerydin (tavaborole) Onychomycosis Indicated for the treatment of onychomycosis due to Trichophyton rubrum and Trichophyton mentagrophytes.

2 . Criteria

Product Name: Jublia [a] or Kerydin [a] Approval Length 48 Week(s) Guideline Type Prior Authorization

Page 718 Approval Criteria

1 - Submission of medical records (laboratory and clinical documentation) confirming diagnosis of onychomycosis of the toenail with of one of the following infections (if request is for a subsequent course of therapy a new test must be performed):

• Trichophyton rubrum • Trichophyton mentagrophytes

AND

2 - Treatment is requested due to medical condition and not for cosmetic purposes (e.g. patients with history of cellulitis of the lower extremity who have ipsilateral toenail onychomycosis, patients with diabetes who have additional risk factors for cellulitis, patients who experience pain/discomfort associated with the infected nail)

AND

3 - History of failure (subject to minimum treatment durations indicated below [b]), contraindication, or intolerance to two of the following antifungal agents (please document date of trial):

• Minimum of 12 week treatment with itraconazole (generic Sporanox) • Minimum of 12 week treatment with oral terbinafine (generic Lamisil) • Minimum of 12 week treatment with ciclopirox (generic Penlac)

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Page 719 program and/or therapeutic class. • Supply limits may be in place. Background: Jublia (efinaconazole) and Kerydin (tavaborole) are both indicated for the treatment of onychomycosis due to Trichophyton rubrum and Trichophyton mentagrophytes. Presence of these organisms may be determined using molecular diagnostic testing. Fungal cultures require a longer turnaround time to obtain diagnosis.

4 . References

1. Jublia Prescribing Information. Valeant Pharmaceuticals North America, LLC. Bridgewater, NJ. September, 2016. 2. Terbinafine Prescribing Information. Dr. Reddy’s Laboratories Limited. Bachupally India. August 2012. 3. Kerydin Prescribing Information. Anacor Pharmaceuticals, Inc., Palo Alto, CA. August 2018. 4. Treating Onychomycosis. Am Fam Physician. 2001 Feb 15;63(4):663-72, 677-8. 5. Sporanox Prescribing Information. Janssen Pharmaceuticals. Titusville, NJ. May 2018. 6. Goldstein AO. Onychomycosis: Management. UpToDate. February 2019. https://www.uptodate.com/contents/onychomycosis- management?search=onychomycosis%20treatment&source=search_result&selectedTitl e=1~87&usage_type=default&display_rank=1 7. Penlac Prescribing Information. Valeant Pharmaceuticals North America LLC. Bridgewater, NJ. June, 2016. 8. Grag J, Tilak R, Sanjay S, et al. Evaluation of Pan-Dermatophyte Nested PCR in Diagnosis of Onychomycosis. 2007. J Clin Microbiology. 45:3443-3445.

5 . Revision History

Date Notes

5/7/2020 Annual review. Updated references.

Page 720 Topical Retinoid Products

Prior Authorization Guideline

GL-88571 Topical Retinoid Products

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 7/26/2017 P&T Revision Date: 01/15/2020 ; 06/17/2020 ; 4/21/2021

1 . Indications Drug Name: Topical retinoid products Cosmetic and medical conditions Indicated for cosmetic and medical conditions (e.g. acne vulgaris, psoriasis, precancerous skin lesions)

2 . Criteria

Product Name: Altreno, Arazlo, Avita, Aklief, Brand Atralin, Brand Differin, Brand Retin-A, Brand Retin-A Micro, Fabior, Generic adapalene, Generic tretinoin gel and lotion, or Generic tretinoin microsphere Approval Length 12 month(s) Guideline Type Prior Authorization or Non-Formulary

Page 721

Approval Criteria

1 - The member has a non-cosmetic medical condition (e.g. acne vulgaris, psoriasis, precancerous skin lesions, other conditions listed below**, etc.)

AND

2 - Medication is not being requested solely for cosmetic purposes (e.g., photoaging, wrinkling, hyperpigmentation, sun damage, melasma)

AND

3 - History of failure or intolerance to both of the following:

• OTC Differin gel • Tretinoin cream (generic Retin-A)

Product Name: Tazorac Approval Length 12 month(s) Guideline Type Prior Authorization or Non-Formulary

Approval Criteria

1 - One of the following criteria:

1.1 All of the following:

1.1.1 Diagnosis of plaque psoriasis

AND

1.1.2 One of the following:

1.1.2.1 History of failure, contraindication, or intolerance to a corticosteroid topical treatment†

Page 722 OR

1.1.2.2 Prescribed by a dermatologist

1.2 All of the following:

1.2.1 Request is for Tazorac 0.1%

AND

1.2.2 The member has a non-cosmetic medical condition other than psoriasis (e.g., acne vulgaris, precancerous skin lesions, other conditions listed below**, etc.)

AND

1.2.3 Medication is not being requested solely for cosmetic purposes (e.g., photoaging, wrinkling, hyperpigmentation, sun damage, melasma)

AND

1.2.4 History of failure or intolerance to both of the following:

• OTC Differin gel • tretinoin cream (generic Retin-A)

3 . Background

Benefit/Coverage/Program Information

** Non-cosmetic medical conditions:

Acanthosis nigricans Keratoderma Acne Keratoderma palmaris et

Page 723 plantaris Acne keloidalis nuchae Keratosis rubra figurata Acne rosacea Kyrle’s disease Acne vulgaris Lamellar ichthyosis Actinic cheilitis Leukoplakia Actinic dermatitis Lichen planus Actinic keratosis Mal de Meleda Basal cell carcinoma Malignancy Bowen’s disease Mendes da Costa syndrome Cystic acne Molluscum contagiosum Darier’s disease Non-bullous congenital ichthyosis Darier-White Disease Papillon-Lefevre syndrome Dermal mucinosis Porokeratosis Discoid lupus Pseudofollicular barbae erythematosis Epidermoid cysts Pseudoacanthosis nigricans Epidermolytic Psoriasis hyperkeratosis Erythrokeratoderma Psoriasis erythrodermic, variabilis palmoplantar Favre Raucochet disease Psoriasis pustular Flat warts Psoriatic arthritis Folliculitis Rosacea Fox Fordyce disease Sebaceous cysts Grover’s disease Senile keratosis Hidradenitis suppurativa Solar keratosis Hyperkeratosis Squamous cell carcinoma Hyperkeratosis follicularis Transient acantholytic dermatosis Hyperkeratotic eczema Tylotic eczema Ichthyoses X-linked ichthyosis Ichthyosis vulgaris Verucca planae Keratoacanthoma Von Zumbusch pustular Keratosis follicularis Warts

† Topical Corticosteroid Therapy:

Potency Brand Name Generic Name Low potency Hytone®, Cortaid® Hydrocortisone acetate Aclovate® Alclometasone DesOwen®, Tridelison® Desonide Kenalog® Triamcinolone acetonide

Page 724 Synalar® Fluocinolone acetonide Valisone® Betamethasone valerate Medium potency Cordran® Flurandrenolide Cutivate® Fluticasone Diprosone® Betamethasone dipropionate Elocon® Mometasone Kenalog® Triamcinolone acetonide Locoid® Hydrocortisone butyrate Synalar® Fluocinolone acetonide Topicort® LP Desoximetasone Westcort® Hydrocortisone valerate High Potency Cyclocort® Amcinonide Diprolene®, Diprolene® Augmented betamethasone dipropionate AF Diprosone® Betamethasone dipropionate Halog® Halcinonide Kenalog® Triamcinolone acetonide Lidex® Fluocinonide Topicort® Desoximetasone Psorcon® Diflorasone diacetate Temovate® Clobetasol propionate Ultravate® Halobetasol propionate Vanos® Fluocinonide Background:

Topical retinoid products are indicated for cosmetic and medical conditions (e.g. acne vulgaris, psoriasis, precancerous skin lesions). Cosmetic use is not a covered benefit. Therefore, Prior Authorization/Notification is in place to verify the use is for the diagnosis of a medical condition. For covered medications if members are younger than 30 years of age the topical retinoid prescription will automatically adjudicate without a coverage review.

Additional Clinical Rules:

4 . References

Page 725 1. Atralin [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC.; July 2016. 2. Avita cream [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; June 2018. 3. Avita gel [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; January 2018. 4. Differin gel [package insert]. Fort Worth, TX: Galderma Laboratories, L.P.; February 2018. 5. Differin lotion [package insert]. Fort Worth, TX: Galderma Laboratories, L.P.; February 2018. 6. Differin cream [package insert]. Fort Worth, TX: Galderma Laboratories, L.P.; February 2018. 7. Retin-A [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC.; June 2018. 8. Retin-A Micro [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC.; October 2017. 9. Tazorac cream [package insert]. Irvine, CA: Allergan; July 2017. 10. Tazorac gel [package insert]. Irvine, CA: Allergan; April 2018. 11. Fabior [package insert]. Research Trinagle Park, NC. Stiefel Laboratories, Inc.; June 2018. 12. Altreno [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC.; November 2019. 13. Aklief cream [package insert]. Fort Worth, TX: Galderma Laboratories, L.P.; October 2019. 14. Arazlo [package insert]. Bridgewater, NJ: Bausch Health Companies Inc.; December 2019.

5 . Revision History

Date Notes

6/17/2021 4/2021 P&T - Added Arazlo as target medication. Updated references.

Page 726 Tresiba (insulin degludec)

Prior Authorization Guideline

GL-14614 Tresiba (insulin degludec)

Formulary UHC Core

Formulary Note

Guideline Note:

Effective Date:

P&T Approval Date:

P&T Revision Date:

Note:

P&T Approval Date: 1/27/2016. According to Texas State Law, all diabetic medications used for the treatment of diabetes shall be covered.

1 . Indications Drug Name: Tresiba (insulin degludec) Diabetes Mellitus Indicated to improve glycemic control in adults with diabetes mellitus. Limitations of Use Tresiba is not recommended for the treatment of diabetic ketoacidosis.

2 . Criteria

Product Name: Tresiba

Page 727 Guideline Type Step Therapy

Approval Criteria

1 - History of both of the following:

• Lantus • Levemir

3 . References

1. Tresiba Prescribing Information. Novo Nordisk, September 2015.

Page 728 Trulance (plecanatide), Zelnorm (tegaserod) - PA/Med Nec

Prior Authorization Guideline

GL-79298 Trulance (plecanatide), Zelnorm (tegaserod) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 3/1/2021 P&T Approval Date: 6/28/2017 P&T Revision Date: 12/18/2019 ; 12/16/2020

1 . Indications Drug Name: Trulance (plecanatide) Chronic idiopathic constipation Indicated for the treatment of chronic idiopathic constipation.

Drug Name: Trulance (plecanatide) Irritable bowel syndrome with constipation (IBC-C) Indicated for the treatment of adults with irritable bowel syndrome with constipation

Drug Name: Zelnorm (tegaserod) Irritable bowel syndrome with constipation (IBC-C) Indicated for treatment of irritable bowel syndrome with constipation in adult women less than 65 years.

2 . Criteria

Page 729

Product Name: Trulance [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 Diagnosis of chronic idiopathic constipation

1.2 Diagnosis of irritable bowel syndrome with constipation

AND

2 - History of failure, contraindication or intolerance to one OTC medication used for the treatment of constipation (document duration of trial)

AND

3 - History of failure, contraindication, or intolerance to Linzess Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Zelnorm [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 730 Approval Criteria

1 - Diagnosis of irritable bowel syndrome with constipation

AND

2 - Patient was female at birth

AND

3 - History of failure, contraindication or intolerance to one OTC medication used for the treatment of constipation (document duration of trial)

AND

4 - History of failure, contraindication, or intolerance to Linzess Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Trulance and Zelnorm [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Page 731

Benefit/Coverage/Program Information

Background:

Linzess (linaclotide) and Trulance (plecanatide) are indicated for the treatment of chronic idiopathic constipation and for the treatment of adults with irritable bowel syndrome with constipation. Zelnorm (tegaserod) is indicated for treatment of irritable bowel syndrome with constipation in adults; however, Zelnorm is only indicated in adult woman less than 65 years. Physicians and patients should periodically assess the need for continued treatment with Linzess, Trulance or Zelnorm.

This prior authorization program is intended to encourage the use of lower cost alternatives and requires a member to try an over-the-counter medication (OTC) for constipation and Linzess before providing coverage for Trulance and Zelnorm.

4 . References

1. Linzess [package insert]. Madison, NJ: Allergan USA, Inc.; September 2020. 2. Trulance [package insert]. Bridgewater, NJ: Bausch Health US, LLC; February 2020. 3. Zelnorm [package insert]. Covington, LA: Alfasigma USA, Inc.; June 2020.

5 . Revision History

Date Notes

1/5/2021 Removed Ibsrela since noted as discontinued on FDA website. Update d references.

Page 732 Uloric (febuxostat) - Step Therapy

Prior Authorization Guideline

GL-71709 Uloric (febuxostat) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 10/1/2020 P&T Approval Date: 8/19/2015 P&T Revision Date: 7/15/2020

1 . Criteria

Product Name: Uloric* [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to both of the following:

• allopurinol (generic Zyloprim) • febuxostat (generic Uloric)

Page 733 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y. * Multi-source brand Uloric is typically excluded from coverage.

Product Name: febuxostat (generic Uloric) [a] Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to allopurinol (generic Zyloprim) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

2 . Background

Benefit/Coverage/Program Information

Background:

Uloric (febuxostat)* is a xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. Uloric* is not recommended for the treatment of asymptomatic hyperuricemia.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try allopurinol before providing coverage for Uloric*. Additional Clinical Rules:

Page 734 3 . References

1. Uloric [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; February 2019.

4 . Revision History

Date Notes

8/17/2020 Annual review. Added addition step criteria for brand Uloric and remov ed look back since excluded product. Added step for febuxostat (gener ic Uloric).

Page 735 Ultravate - Step Therapy

Prior Authorization Guideline

GL-67154 Ultravate - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2020 P&T Approval Date: 3/18/2020 P&T Revision Date: 03/18/2020

1 . Criteria

Product Name: Ultravate (halobetasol propionate 0.05% lotion) [a] Diagnosis Super Potent (group I) Approval Length 12 month(s) Guideline Type Step Therapy

Approval Criteria

1 - History of failure, contraindication or intolerance to both of the following:

• augmented betamethasone dipropionate 0.05% gel or lotion (generic Diprolene)

Page 736 • clobetasol propionate 0.05% gel or solution (generic Temovate)

2 . Background

Clinical Practice Guidelines

Topical Steroids Potency Class:

Potency Class Step 1 medications Step 2 medications

Super Potent (group -augmented betamethasone -Ultravate (halobetasol I) dipropionate 0.05% gel or propionate lotion 0.05% lotion) (generic Diprolene)

-clobetasol propionate 0.05% gel or solution (generic Temovate)

Benefit/Coverage/Program Information

Background:

Topical steroids are commonly prescribed for the treatment of rash, eczema, and dermatitis. Topical steroids have anti-inflammatory properties, and are classified into different potency classes based on their vasoconstriction abilities. A vasoconstriction bioassay provides potency measurements that correlate with clinical potency. There are numerous topical steroid products.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try one or two lower cost alternative topical steroids before providing coverage for higher cost topical steroids. Generic equivalent medications for brands listed as a step 2 agent will also be targeted when available.

Class 1: Super Potent Class 5: Lower Mid-Strength Class 2: Potent Class 6: Mild

Page 737 Class 3: Upper Mid- Strength Class 7: Least Potent Class 4:Mid-Strength Additional Clinical Rules: • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. • Supply limits may be in place.

3 . References

1. Tadicherla, Sujatha, et al. "Topical corticosteroids in dermatology." Journal of drugs in dermatology 8.12 (2009):1093-1105. 2. Psoriasis.org. 2019. Topical steroid potency chart - National Psoriasis Foundation. [online] Available at: https://www.psoriasis.org/about- psoriasis/treatments/topicals/steroids/potency-chart [Accessed: February 2, 2020]. 3. Uptodate.com. 2020. Topical corticosteroids. [online] Available at: https://www.uptodate.com/contents/image?imageKey=DERM%2F62402&topicKey=DER M%2F5565&search=topical%20corticosteroid%20potency&rank=1~150&source=see_lin k [Accessed: February 7, 2020]. 4. Menter, Alan, et al. "Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies." Journal of the American Academy of Dermatology 60.4 (2009):643-659.

4 . Revision History

Date Notes

5/29/2020 03/2020 P&T - New program.

Page 738 Upneeq (oxymetazoline) - PA/Med Nec

Prior Authorization Guideline

GL-79338 Upneeq (oxymetazoline) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 3/1/2021 P&T Approval Date: 12/16/2020

P&T Revision Date:

1 . Indications Drug Name: Upneeq (oxymetazoline) Blepharoptosis Indicated for the treatment of acquired blepharoptosis in adults.

2 . Criteria

Product Name: Upneeq [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 739 Approval Criteria

1 - Diagnosis of acquired blepharoptosis

AND

2 - Patient has a functional impairment related to the position of the eyelid

AND

3 - One of the following:

• Marginal reflex distance-1 (MRD-1) is less than or equal to 2 mm in primary gaze • Marginal reflex distance-1 (MRD-1) is less than or equal to 2 mm in down gaze • Superior visual field loss of at least 12 degrees or 24 percent

AND

4 - Other treatable causes of blepharoptosis have been ruled out (e.g., recent botulinum toxin injections, myasthenia gravis)

AND

5 - Prescribed by or in consultation with one of the following:

• Optometrist • Ophthalmologist

Product Name: Upneeq [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 740

Approval Criteria

3 . Background

Benefit/Coverage/Program Information

Background: Upneeq (oxymetazoline) 0.1% ophthalmic solution is indicated for the treatment of acquired blepharoptosis in adults.

Coverage will be provided for members who meet the following criteria. Additional Clinical Rules:

4 . References

1. Upneeq [package insert]. Bridgewater, NJ: RVL Pharmaceuticals, Inc.; August 2020. 2. Charles B. Slonim, MD; Shane Foster, OD; Mark Jaros, PhD;, et. al. Association of Oxymetazoline Hydrochloride, 0.1% Solution Administration with Visual Field in Acquired Ptosis A Pooled Analysis of 2 Randomized Clinical Trials. JAMA Ophthalmol. October 2020.

5 . Revision History

Date Notes

Page 741 1/7/2021 New program.

Page 742 Vascepa (icosapent ethyl)* - PA/Med Nec

Prior Authorization Guideline

GL-84763 Vascepa (icosapent ethyl)* - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 2/14/2020 P&T Revision Date: 10/21/2020 ; 12/16/2020 ; 3/17/2021

1 . Indications Drug Name: Vascepa Cardiovascular Risk Reduction Indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and either established cardiovascular disease or diabetes mellitus and 2 or more additional risk factors for cardiovascular disease. Also indicated as adjunctive therapy to diet and exercise to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

2 . Criteria

Product Name: Vascepa* [a] Diagnosis Cardiovascular Risk Reduction

Page 743 Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Vascepa will be approved based on all of the following criteria:

1.1 Diagnosis of Hypertriglyceridemia (pre-treatment triglyceride level ≥ 150mg/dL)

AND

1.2 Patient currently has or is considered high or very high risk for cardiovascular disease (CVD) as evidenced by one of the following:

1.2.1 Both of the following:

1.2.1.1 Age ≥ 45

AND

1.2.1.2 Established CVD confirmed by one of the following:

• Acute coronary syndrome • History of myocardial infarction • Stable or unstable angina • Coronary or other arterial revascularization • Stroke • Transient ischemic attack • Peripheral arterial disease

1.2.2 All of the following:

1.2.2.1 Diagnosis of Type 2 diabetes

AND

Page 744

1.2.2.2 Two of the following risk factors for developing cardiovascular disease:

• Men ≥ 55 years and women ≥ 65 years • Cigarette smoker or stopped smoking within the past 3 months • Hypertension (pretreatment blood pressure ≥ 140 mmHg systolic or ≥ 90 mmHg diastolic) • HDL-C ≤ 40 mg/dL for men or ≤ 50 mg/dL for women • High-sensitivity C-reactive protein > 3.0 mg/L • Creatinine clearance > 30 and < 60 mL/min • Retinopathy • Micro- or macro-albuminuria • Ankle-brachial index (ABI) <0.9 without symptoms of intermittent claudication

AND

1.3 Submission of medical records (e.g., chart notes, laboratory values) documenting one of the following (prescription claims history may be used in conjunction as documentation of medication use, dose, and duration):

1.3.1 Patient has been receiving at least 12 consecutive weeks of high-intensity statin therapy (i.e. atorvastatin 40-80 mg, rosuvastatin 20-40 mg) and will continue to receive a high-intensity statin at maximally tolerated dose

1.3.2 Both of the following:

1.3.2.1 Patient is unable to tolerate high-intensity statin as evidenced by one of the following intolerable and persistent (i.e. more than 2 weeks) symptoms:

• Myalgia (muscle symptoms without CK elevations) • Myositis (muscle symptoms with CK elevations < 10 times upper limit of normal [ULN])

AND

1.3.2.2 One of the following:

1.3.2.2.1 Patient has been receiving at least 12 consecutive weeks of moderate-intensity [i.e. atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin ≥ 20 mg, pravastatin ≥ 40 mg, lovastatin 40 mg, fluvastatin XL 80 mg, fluvastatin 40 mg twice daily or Livalo (pitavastatin) ≥ 2 mg] statin therapy and will continue to receive a moderate-intensity statin at maximally tolerated dose

Page 745

1.3.2.2.2 Patient has been receiving at least 12 consecutive weeks of low-intensity [i.e. simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg, fluvastatin 20-40 mg, or Livalo (pitavastatin) 1 mg] statin therapy and will continue to receive a low-intensity statin at maximally tolerated dose

AND

1.4 Submission of medical record (e.g., chart notes, laboratory values) documenting one of the following (prescription claims history may be used in conjunction as documentation of medication use, dose, and duration):

1.4.1 Patient has been receiving at least 12 consecutive weeks of ezetimibe (Zetia) therapy as adjunct to maximally tolerated statin therapy

1.4.2 Patient has a history of contraindication or intolerance to ezetimibe

1.4.3 Patient has a LDL-C less than 100 mg/dL while on maximally tolerated statin therapy

AND

1.5 Used as an adjunct to a low-fat diet and exercise

AND

1.6 Prescribed by or in consultation with one of the following:

• Cardiologist • Endocrinologist • Lipid specialist

Page 746

AND

1.7 Prescriber attests to the following: the information provided is true and accurate to the best of their knowledge and they understand that UnitedHealthcare may perform a routine audit and request the medical information necessary to verify the accuracy of the information provided Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Vascepa* [a] Diagnosis Cardiovascular Risk Reduction Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Vascepa will be approved based on all of the following criteria:

1.1 Used for cardiovascular risk reduction

AND

1.2 Documentation of positive clinical response to therapy

AND

1.3 Patient is on an appropriate low-fat diet and exercise regimen

AND

1.4 Patient is receiving maximally tolerated statin therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage

Page 747 criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background

Vascepa® (icosapent ethyl)* is indicated as adjunctive therapy to diet and exercise to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Vascepa* is also indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and either established cardiovascular disease or diabetes mellitus and 2 or more additional risk factors for cardiovascular disease.

Since the Pharmacy & Therapeutics Committee has determined that use of Vascepa* is not medically necessary for treatment of severe hypertriglyceridemia (TG ≥ 500 mg/dL), coverage of Vascepa* will only be provided for cardiovascular risk reduction after meeting these requirements.

Additional Clinical Rules:

* Lovaza (multi-source brand only) and Vascepa (brand and generic) are typically excluded from coverage. Tried/Failed criteria may be in place. Please refer to plan specifics to determine exclusion status.

4 . References

1. Vascepa [package insert]. Bridgewater, NJ: Amarin Pharma Inc.; December 2019. 2. Orringer, CE, Jacobson, TA, Maki, KC. National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk. J Clin Lipidol. 2019;13(6):860-72.

Page 748

5 . Revision History

Date Notes

4/6/2021 Modified pre-treatment triglyceride levels for cardiovascular risk reducti on. Noted that Vascepa is typically excluded from coverage.

Page 749 Vecamyl (mecamylamine)

Prior Authorization Guideline

GL-68938 Vecamyl (mecamylamine)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2020 P&T Approval Date: 5/21/2014 P&T Revision Date: 6/17/2020

1 . Indications Drug Name: Vecamyl (mecamylamine) Moderately Severe to Severe Essential Hypertension Indicated for the management of moderately severe to severe essential hypertension and uncomplicated cases of malignant hypertension.

2 . Criteria

Product Name: Vecamyl Diagnosis Hypertension Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 750 Guideline Type Notification

Approval Criteria

1 - One of the following:

1.1 Diagnosis of moderately severe to severe essential hypertension

1.2 Diagnosis of uncomplicated malignant hypertension

Product Name: Vecamyl Diagnosis Hypertension Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Notification

Approval Criteria

1 - Documentation of a positive clinical response to Vecamyl therapy

3 . Background

Benefit/Coverage/Program Information

Background:

Vecamyl (mecamylamine) is indicated for the management of moderately severe to severe essential hypertension and uncomplicated cases of malignant hypertension.[1] Vecamyl was originally approved under the brand name Inversine, which was launched in the 1950s. The product was withdrawn in September 2009; withdrawal was not due to safety concerns. As of March 2013, the FDA issued an approval for mecamylamine to be re-marketed in the United States.[2]

Additional Clinical Rules:

Page 751 Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and re-authorization based solely on previous claim/medication history, diagnosis codes (ICD-10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class.

4 . References

1. Vecamyl Prescribing Information. Vyera Pharmaceuticals, LLC. New York, NY. July 2018. 2. U.S. Food and Drug Administration website. www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=2 04054. Accessed April 29, 2020.

5 . Revision History

Date Notes

7/14/2020 Annual review. Added reference for mecamylamine history.

Page 752 Veregen (sinecatechins) - Step Therapy

Prior Authorization Guideline

GL-73242 Veregen (sinecatechins) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 11/1/2020 P&T Approval Date: 6/17/2020

P&T Revision Date:

1 . Indications Drug Name: Veregen (sinecatechins) Warts Indicated for the treatment of external genital and perianal warts in immunocompetent patients.

2 . Criteria

Product Name: Veregen [a] Approval Length 4 month(s) Guideline Type Step Therapy

Page 753 Approval Criteria

1 - Patient has a history of failure, contraindication, or intolerance to one of the following:

• Imiquimod (generic Aldara) • Podofilox (generic Conylox)

3 . Background

Benefit/Coverage/Program Information

Background:

Veregen (sinecatechins) is indicated for the treatment of external genital and perianal warts in immunocompetent patients.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try imiquimod or podofilox prior to receiving coverage for Veregen.

Additional Clinical Rules:

4 . References

1. Veregen [package insert]. Melville, NY: Fougera Pharmaceuticals Inc.; December 2019. 2. CDC MMWR Sexually Transmitted Diseases Treatment Guidelines, 2015. June 5, 2015.

Page 754 Verquvo (vericiguat) – PA/Med Nec

Prior Authorization Guideline

GL-90381 Verquvo (vericiguat) – PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 6/16/2021

P&T Revision Date:

1 . Indications Drug Name: Verquvo (vericiguat) Risk of cardiovascular death and heart failure (HF) Indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or the need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%. Verquvo has a boxed warning for embryo-fetal toxicity and should not be used during pregnancy.

2 . Criteria

Product Name: Verquvo Approval Length 12 month(s) Therapy Stage Initial Authorization

Page 755 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of heart failure

AND

2 - Ejection fraction is less than 45 percent

AND

3 - Heart failure is classified as one of the following:

• New York Heart Association Class II • New York Heart Association Class III • New York Heart Association Class IV

AND

4 - One of the following:

• Hospitalization for heart failure within the past six months • Outpatient IV diuretics for heart failure within the past three months

AND

5 - One of the following:

• Patient is on a stabilized dose and receiving concomitant therapy with a maximally tolerated beta-blocker (e.g. bisoprolol, carvedilol, metoprolol) • Patient has a contraindication or intolerance to beta-blocker therapy

AND

6 - One of the following:

Page 756 6.1 Patient is on a stabilized dose and receiving concomitant therapy with one of the following:

• angiotensin converting enzyme (ACE) inhibitor (e.g. captopril, enalapril) • angiotensin II receptor blocker (ARB) (e.g. candesartan, valsartan) • angiotensin receptor-neprilysin inhibitor (ARNI) (e.g. Entresto)

6.2 Patient has an allergy, contraindication, or intolerance to ACE inhibitors, ARBs, and ARNIs.

AND

7 - One of the following:

• Patient is on a stabilized dose and receiving concomitant therapy with a maximally tolerated aldosterone antagonist (e.g. eplerenone, spironolactone) • Patient has a contraindication or intolerance to aldosterone antagonist therapy

AND

8 - One of the following:

• Patient is on a stabilized dose and receiving concomitant therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (e.g. Jardiance) • Patient has a contraindication or intolerance to SGLT2 inhibitor therapy

AND

9 - Verquvo is prescribed by or in consultation with a cardiologist

Product Name: Verquvo Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Page 757 Approval Criteria

1 - Documentation of positive clinical response to therapy

3 . Background

Benefit/Coverage/Program Information

Background: Verquvo (vericiguat) is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or the need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%. Verquvo has a boxed warning for embryo-fetal toxicity and should not be used during pregnancy. Additional Clinical Rules:

4 . References

1. Verquvo [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; January 2021. 2. American Diabetes Association. Standard of Medical Care in Diabetes- 2019. Diabetes Care 2020;43 (Supplement 1) 3. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137- e161 4. Maddox TM, Januzzi JL Jr., Allen LA, Breathett K, Butler J, Davis LL, Fonarow GC, Ibrahim NE, Lindenfeld J, Masoudi FA, Motiwala SR, Oliveros E, Patterson JH, Walsh MN, Wasserman A, Yancy CW, Youmans QR. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021;77:772–810.

5 . Revision History

Page 758 Date Notes

7/30/2021 New program

Page 759 Viberzi (eluxadoline) - PA/Med Nec

Prior Authorization Guideline

GL-84834 Viberzi (eluxadoline) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 4/27/2016 P&T Revision Date: 03/18/2020 ; 3/17/2021

1 . Indications Drug Name: Viberzi (eluxadoline) Irritable bowel syndrome with diarrhea (IBS-D) Indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults

2 . Criteria

Product Name: Viberzi [a] Diagnosis Irritable bowel syndrome with diarrhea (IBS-D) Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 760

Approval Criteria

1 - Diagnosis of irritable bowel syndrome with diarrhea (IBS-D)

AND

2 - History of failure, contraindication or intolerance to a tricyclic antidepressant (e.g. amitriptyline). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y

Product Name: Viberzi [a] Diagnosis Irritable bowel syndrome with diarrhea (IBS-D) Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Viberzi therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y

3 . Background

Benefit/Coverage/Program Information

Background Viberzi (eluxadoline) is a mu-opioid receptor agonist, indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

Page 761 Additional Clinical Rules:

4 . References

1. Viberzi Prescribing Information. Madison, NJ:Allergan USA, Inc.; June 2018. 2. Lacey, BE, Pimentel, M, Brenner, DM, et. al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol. 2021; 116 (1): 17-44 Pietrzak, A., Skrzydło-Radomańska, S., Mulak, A., et. al. Guidelines on the management of irritable bowel syndrome. Gastroenterology. 2018; 13(4):259-288

5 . Revision History

Date Notes

4/6/2021 Annual review. Removed antispasmodic and antidiarrheal agent as a s tep 1 option based on updated ACG guidelines.

Page 762 Vyleesi (bremelanotide) - PA/Med Nec

Prior Authorization Guideline

GL-58181 Vyleesi (bremelanotide) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 2/1/2020 P&T Approval Date: 11/15/2019

P&T Revision Date:

1 . Indications Drug Name: Vyleesi (bremelanotide) Generalized hypoactiv sexual desire disorder (HSDD) indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance.

2 . Criteria

Product Name: Vyleesi Approval Length 2 month(s) Therapy Stage Initial Authorization

Page 763 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of one of the following:

1.1 Acquired, generalized hypoactive sexual desire disorder (HSDD)

1.2 Female sexual interest/arousal disorder

AND

2 - Symptoms of HSDD or female sexual interest/arousal disorder have persisted for at least 6 months

AND

3 - Low sexual desire is NOT due to any of the following:

• A co-existing medical or psychiatric condition • Problems within the relationship • The effects of a medication or other drug substance

AND

4 - Patient was female at birth

AND

5 - Patient is premenopausal

AND

Page 764 6 - Patient does not have uncontrolled hypertension

AND

7 - Patient does not have known cardiovascular disease Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Vyleesi Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Vyleesi therapy

AND

2 - Patient continues to be premenopausal Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

3. Additional Clinical Rules:

Page 765 10) and/or claim logic. Use of automated approval and re-approval processes varies by program and/or therapeutic class. Background:

Vyleesi is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner. Vyleesi is not indicated for the treatment of HSDD in postmenopausal women or in men and is not indicated to enhance sexual performance.

4 . References

1. Vylessi Prescribing Information. AMAG Pharmaceutical, Inc, June 2019. 2. Sexual dysfunctions. In: Diagnostic and Statistical Manual of Mental Disorders, 5th ed., American Psychiatric Association, Arlington, Virginia 2013. 3. Overview of sexual dysfunction in women: Management. UpToDate. Updated July 18, 2019. Last accessed September 23, 2019.

5 . Revision History

Date Notes

12/19/2019 New program.

Page 766 Weight Loss Agents - Prior Authorization - California, Maryland, and New York Regulatory Program

Prior Authorization Guideline

GL-87162 Weight Loss Agents - Prior Authorization - California, Maryland, and New York Regulatory Program

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 11/18/2015 P&T Revision Date: 09/16/2019 ; 11/15/2019 ; 11/13/2020 ; 4/21/2021

1 . Criteria

Product Name: benzphetamine, diethylpropion, phendimetrazine, phentermine (Includes both brand and generic versions and all formulations of the listed products unless otherwise noted) Approval Length 3 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Treatment is being requested for weight loss

Page 767

AND

2 - Patient is greater than 16 years of age

AND

3 - Failure to lose greater than or equal to 5% of body weight after at least 6 months of lifestyle modification alone (e.g., dietary or caloric restriction, exercise, behavioral support, community- based program). Document lifestyle modifications employed and total weight loss

AND

4 - One of the following:

• Failure to lose greater than or equal to 5% of body weight after six months of treatment with OTC orlistat (Alli) (document date of trial of orlistat and total body weight lost) • Contraindication (including age) or intolerance to OTC orlistat (Alli)

AND

5 - Used as an adjunct to lifestyle modification. Document which lifestyle modification will be employed.

AND

6 - One of the following:

6.1 Body Mass Index (BMI) greater than or equal to 40 kg/m2 (Obesity Class III). Documentation of current height and weight required.

6.2 Both of the following:

6.2.1 BMI greater than or equal to 30 kg/m2 (Obesity Class I). Documentation of current height and weight required

Page 768

AND

6.2.2 Documentation of a weight-related comorbidity(examples include dyslipidemia, hypertension, type 2 diabetes, sleep apnea)

Product Name: benzphetamine, diethylpropion, phendimetrazine, phentermine (Includes both brand and generic versions and all formulations of the listed products unless otherwise noted) Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of current weight showing a weight loss of greater than or equal to 5% of baseline body weight

AND

2 - Documentation of continuation of lifestyle modification

Product Name: Xenical, Contrave, or Qsymia (Includes both brand and generic versions and all formulations of the listed products unless otherwise noted): Approval Length Contrave: 4 Months; Qsymia, Xenical: 6 Months Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Treatment is being requested for weight loss

AND

2 - One of the following:

Page 769 • Patient is greater than or equal to 12 years of age for Xenical • Patient is greater than or equal to 18 years of age for Contrave, Qsymia

AND

3 - Failure to lose greater than or equal to 5% of body weight through at least 6 months of lifestyle modification alone (e.g., dietary or caloric restriction, exercise, behavioral support, community-based program). Document lifestyle modifications employed and total weight loss.

AND

4 - One of the following:

AND

5 - Used as an adjunct to lifestyle modification. Document which lifestyle modification will be employed.

AND

6 - One of the following:

6.1 Body Mass Index (BMI) greater than or equal to 40 kg/m2 (Obesity Class III) Documentation of current height and weight required.

6.2 Both of the following:

6.2.1 BMI greater than or equal to 30 kg/m2 (Obesity Class I) Documentation of current height and weight required.

Page 770 AND

6.2.2 Documentation of a weight-related comorbidity(examples include dyslipidemia, hypertension, type 2 diabetes, sleep apnea)

Product Name: Xenical, Contrave, or Qsymia (Includes both brand and generic versions and all formulations of the listed products unless otherwise noted): Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of current weight showing a weight loss of greater than or equal to 5% of baseline body weight

AND

2 - Documentation of continuation of lifestyle modification

Product Name: Saxenda Approval Length 4 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Treatment is being requested for weight loss

AND

2 - Patient is greater than or equal to 18 years of age

Page 771 AND

AND

4 - Both of the following:

4.1 One of the following:

AND

4.2 Contraindication, intolerance or failure to lose and maintain greater than or equal to 5% body weight following 3 month trial EACH, of two of the following medications (document date of trial of each medication and total body weight lost):

• Prescription Xenical • Qsymia • Contrave

AND

5 - Used as an adjunct to lifestyle modification. Document which lifestyle modification will be employed.

AND

6 - One of the following:

6.1 Body Mass Index (BMI) greater than or equal to 40 kg/m2 (Obesity Class III). Documentation of current height and weight required.

Page 772 OR

6.2 Both of the following:

6.2.1 BMI greater than or equal to 30 kg/m2 (Obesity Class I). Documentation of current height and weight required.

AND

6.2.2 Documentation of a weight-related comorbidity (examples include dyslipidemia, hypertension, type 2 diabetes, sleep apnea)

Product Name: Saxenda Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of current weight showing a weight loss of greater than or equal to 5% of baseline body weight

AND

2 - Documentation of continuation of lifestyle modification

Product Name: Imcivree Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of obesity is due to POMC, PCSK1, or LEPR gene deficiency

Page 773

AND

2 - One of the following:

2.1 Adult patient with BMI ≥ 30 kg/m2

2.2 Pediatric patient with weight > 95th percentile for age on growth chart assessment

AND

3 - Genetic testing confirming variants in POMC, PCSK1, or LEPR genes interpreted as pathogenic, likely pathogenic, or of uncertain significance

AND

4 - Patient is currently enrolled in or has history of a weight loss management program

Product Name: Imcivree Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - One of the following:

1.1 If on therapy for less than 12 months, documentation of a positive clinical response to Imcivree therapy defined as weight loss ≥5% of baseline weight

Page 774 1.2 If on therapy for ≥12 months, documentation of a positive clinical response to Imcivree therapy defined as ≥10% weight loss from baseline

2 . Background

Benefit/Coverage/Program Information

Background:

Anti-obesity agents are indicated in the management of obesity as an adjunct to lifestyle modifications including diet, exercise and behavioral modification. Medication therapy may provide modest weight reduction in conjunction with lifestyle modifications and therapy selection may be based on a specific medications side effects and warnings.

Body Mass Index (BMI) uses weight and height to create an index of underweight, overweight or obesity in adults. The international classification is as follows:

WHO Global Database on Body Mass Index

Classification BMI(kg/m2)

Underweight < 18.50

Normal range 18.50 - 24.99

Overweight ≥ 25.00

Obese ≥ 30.00

Obese class I 30.00 - 34.99

Obese class II 35.00 - 39.99

Obese class III ≥ 40.00

This program uses Obese Class III and Obese Class I (with weight related comorbidities) as markers for coverage and is designed to meet regulatory requirements for coverage of weight loss medications in Maryland and New York and morbid obesity in California.

Additional Clinical Rules:

• Supply limits may be in place

Page 775 3 . References

1. AACE position statement on obesity and obesity medicine. September/October 2012. 2. National Institutes of Health, National Heart, Lung, and Blood Institute, and North American Association for the Study of Obesity. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. 2000. 3. American Gastroenterological Association medical position statement on obesity. Gastroenterology 2002 Sep;123(3):879-81. 4. Bray, GA, Ryan, DH. Medical Therapy for the Patient with Obesity. Circulation. 2012;125:1695-1703. 5. Barlow, SE. Expert Committee Recommendations Regarding the Prevention, Assessment, and Treatment of Child and Adolescent Overweight and Obesity: Summary Report. Pediatrics 2007. 6. Benzphetamine [package insert]. HJ Harkins Company, Inc.; Heritage Pharmaceuticals. December 2019. 7. Diethylpropion [package insert]. Philadelphia, PA: Lannett Company, Inc. December 2019. 8. Phendimetrazine Slow-Release Capsules [package insert]. Princeton, NJ: Sandoz Inc. ; November 2018. 9. Adipex-P [package insert]. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; March 2020. 10. Xenical [package insert]. South San Francisco, CA: Roche Pharmaceuticals; September 2020. 11. Qsymia [package insert]. Mountain View, CA. Vivus Inc.; March 2018. 12. Contrave [package insert]. Deerfield, IL: Takeda Pharmaceuticals Inc.; September 2014. 13. Saxenda [package insert]. Plainsboro, NJ: Novo Nordisk; March 2020. 14. Bray, GA. Obesity in Adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on September 14, 2015.) 15. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497. 16. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism 2015 100:2, 342-362 17. AHA/ACC/TOS Prevention Guideline: 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report to the American College of Cardiology/American Health Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014; 129:S102-138 18. World Health Organization. (2006). Global Database on Body Mass Index. Retrieved from http://apps.who.int/bmi/index.jsp?introPage=intro_3.html 19. Lomaira [package insert]. Newtown, PA: KVK-Tech, Inc.; December 2018. 20. Imcivree [package insert]. Boston, MA : Rhythm Pharmaceuticals, Inc ; November 2020.

4 . Revision History

Date Notes

Page 776 5/19/2021 Added Imcivree as in scope. Added Imcivree criteria. Updated referenc es. Formatting changes.

Page 777 Winlevi (clascoterone) - PA/Med Nec

Prior Authorization Guideline

GL-90417 Winlevi (clascoterone) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 6/16/2021

P&T Revision Date:

1 . Indications Drug Name: Winlevi (clascoterone) Acne Vulgaris Indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

2 . Criteria

Product Name: Winlevi [a] Approval Length 6 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 778

Approval Criteria

1 - Diagnosis of acne vulgaris

AND

2 - Patient is 12 years of age or older

AND

3 - History of failure, contraindication, or intolerance to an adequate trial of a topical retinoid [(e.g. tretinoin (generic Retin-A)]

AND

4 - History of failure, contraindication, or intolerance to an adequate trial of a topical antibiotic in combination with benzoyl peroxide [e.g., benzoyl peroxide/clindamycin (generic Duac), benzoyl peroxide/erythromycin (generic Benzamycin)]

AND

5 - History of failure, contraindication, or intolerance to an adequate trial of a topical dapsone (e.g. Aczone). Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Winlevi [a] Approval Length 6 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

Page 779

1 - Documentation of positive clinical response to therapy

AND

2 - Patient has been assessed for signs of hypothalamus-pituitary-adrenal (HPA) axis suppression (e.g. fatigue, weight loss, abdominal pain, depression, muscle weakness) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background: Winlevi (clascoterone) is an androgen receptor inhibitor indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. Guidelines from the American Academy of Dermatology recommend topical therapies including retinoids, antibiotics in combination with benzoyl peroxide, azelaic acid and dapsone for mild to moderate acne. Systemic antibiotics are first-line in moderate to severe acne with concomitant topical therapy of benzoyl peroxide or a retinoid. Additional Clinical Rules:

4 . References

1. Winlevi [package insert]. Milan, Italy: Cassiopea, Inc; August 2020. 2. Zaenglein, Andrea L. et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. May 2016;74(5):945–973.e33

5 . Revision History

Page 780

Date Notes

7/31/2021 New program

Page 781 Xifaxan (rifaximin) - PA/Med Nec

Prior Authorization Guideline

GL-87094 Xifaxan (rifaximin) - PA/Med Nec

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 7/1/2021 P&T Approval Date: 8/20/2014 P&T Revision Date: 04/15/2020 ; 4/21/2021

1 . Indications Drug Name: Xifaxan (rifaximin) Travelers' diarrhea Indicated for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients 12 years of age and older.

Hepatic encephalopathy Indicated for the risk reduction of hepatic encephalopathy recurrence in adults.

Irritable bowel syndrome with diarrhea Indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D).

Off Label Uses: Inflammatory bowel diseases There is some limited data to support the off label use of Xifaxan for the treatment of inflammatory bowel diseases.

2 . Criteria

Page 782

Product Name: Xifaxan [a] Diagnosis Travelers' Diarrhea Approval Length 1 month(s) Guideline Type Prior Authorization

Approval Criteria

1 - Travelers' diarrhea

AND

2 - History of failure, contraindication, or intolerance to one of the following:

• Azithromycin (generic Zithromax) • Ciprofloxacin (generic Cipro) • Levofloxacin (generic Levaquin) • Ofloxacin (generic Floxin)

Product Name: Xifaxan [a] Diagnosis Hepatic Encephalopathy Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Hepatic Encephalopathy

AND

Page 783 2 - One of the following

2.1 Both of the following

2.1.1 Used as add-on therapy to lactulose

AND

2.1.2 Patient is unable to achieve an optimal clinical response with lactulose monotherapy

2.2 History of contraindication or intolerance to lactulose Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Xifaxan [a] Diagnosis Hepatic Encephalopathy Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Xifaxan therapy Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Xifaxan [a] Diagnosis Irritable Bowel Syndrome with diarrhea (IBS-D) Approval Length 14 Day(s) Therapy Stage Initial Authorization

Page 784 Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of IBS-D

AND

2 - History of failure, contraindication, or intolerance to a tricyclic antidepressant (e.g. amitriptyline) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

Product Name: Xifaxan [a] Diagnosis Irritable Bowel Syndrome with diarrhea (IBS-D) Approval Length 14 Day(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Patient has experienced a recurrence of IBS-D after a prior 14 day course of therapy with Xifaxan

AND

2 - Patient has had a treatment-free period between courses of therapy

AND

3 - Patient has not already received 3 treatment courses of Xifaxan for IBS-D in the previous 6 months Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage

Page 785 criteria. Other policies and utilization management programs may appl y.

Product Name: Xifaxan [a] Diagnosis Inflammatory Bowel Disease (e.g., Crohn's Disease, Ulcerative Colitis, Diverticulitis) [Off Label] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Approval Criteria

1 - Diagnosis of Inflammatory Bowel Disease

AND

2 - History of failure, contraindication or intolerance to both of the following:

• Ciprofloxacin (generic Cipro) • Metronidazole (generic Flagyl)

Product Name: Xifaxan [a] Diagnosis Inflammatory Bowel Disease (e.g. Crohn's Disease, Ulcerative Colitis, Diverticulitis) (Off Label) Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

1 - Documentation of positive clinical response to Xifaxan therapy

Page 786 Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Additional Clinical Rules:

Xifaxan is an antibacterial agent indicated for the treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli in patients 12 years of age and older, for the risk reduction of hepatic encephalopathy recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D). There is some limited data to support the off label use of Xifaxan for the treatment of inflammatory bowel diseases.

This program requires a member to try an alternative antimicrobial agent before providing coverage for Xifaxan for traveler’s diarrhea and for inflammatory bowel disease, lactulose before providing coverage for Xifaxan as add-on therapy for hepatic encephalopathy, or an antispasmodic agent, an antidiarrheal agent and/or a tricyclic antidepressant before providing coverage for Xifaxan for IBS-D. Members utilizing Xifaxan 200 mg for Travelers’ Diarrhea will automatically be approved if prescribed for a one-time dose of 9 tablets.

4 . References

1. Xifaxan [package insert]. Bridgewater, NJ: Bausch Health US, LLC; October 2020. 2. Prantera C, et. Al. Antibiotic treatment of Crohn's disease: results of a multicenter, double blind, randomized, placebo-controlled trial with rifaximin. Aliment Pharmacol Ther 2006 April 15;23(8): 1117-25 3. Scherl EJ. Bacteria, bugs and BID rifaximin for Crohn's disease. Inflamm Bowel Dis 2007 June;13(6):800-1. 4. LaRocque, R. Travelers’s diarrhea: Clinical manifestations, diagnosis, and treatment. In:UpToDate, Calderwood, SB (Ed), UpToDate. Waltham, MA. (Accessed on March 1, 2021).

Page 787 5. Pimentel H, Lembo A, Chey W, et al: Rifaximin therapy for patients with Irritable Bowel Syndrome without constipation. N Engl J Med 2011; 364(1):22-32 6. Lacey, BE, Pimentel, M, Brenner, DM, et. al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol. 2021; 116 (1): 17-44American 7. American Gastroenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome. 2014. 8. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60:715-735.

5 . Revision History

Date Notes

5/18/2021 Annual review. Removed antispasmodic and antidiarrheal agent as a s tep 1 option for IBS-D based on updated ACG guidelines. Added reaut horization for hepatic encephalopathy. Updated references.

Page 788 Zileuton extended-release (generic Zyflo CR) , Zyflo (zileuton) - Step Therapy

Prior Authorization Guideline

GL-81844 Zileuton extended-release (generic Zyflo CR) , Zyflo (zileuton) - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 9/1/2021 P&T Approval Date: 2/26/2016 P&T Revision Date: 03/18/2020 ; 2/19/2021

1 . Indications Drug Name: Zileuton extended-release (generic Zyflo CR), Zyflo (zileuton) Asthma Indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.

2 . Criteria

Product Name: Zileuton extended-release (generic Zyflo CR) or Zyflo [a] Diagnosis Asthma Approval Length 12 month(s) Guideline Type Step Therapy

Page 789

Approval Criteria

1 - One of the following:

1.1 History of therapeutic failure to one of the following:

• montelukast (generic Singulair)* • zafirlukast (generic Accolate)

1.2 Contraindication or intolerance to both of the following:

• montelukast (generic Singulair)* • zafirlukast (generic Accolate)

Notes *Brand Singulair tablets and chewable tablets are typically excluded fro m coverage. Tried/Failed criteria may be in place. Please refer to plan specifics to determine exclusion status. [a] State mandates may apply. Any federal regulatory requirements and the member specific benefit pl an coverage may also impact coverage criteria. Other policies and utili zation management programs may apply.

3 . Background

Benefit/Coverage/Program Information

Background: Zileuton extended-release (generic Zyflo CR) and Zyflo (zileuton) are leukotriene modifiers indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try either montelukast (generic Singulair) or zafirlukast (generic Accolate) prior to receiving coverage for Zyflo or Zyflo CR.

Page 790 Members, who have received at least a 90 day supply of zileuton extended-release (generic Zyflo CR), or Zyflo in the past 120 days as documented in claims history, will be allowed continued coverage of their current therapy. Additional Clinical Rules:

*Brand Singulair tablets and chewable tablets are typically excluded from coverage. Tried/Failed criteria may be in place. Please refer to plan specifics to determine exclusion status.

4 . References

1. Global Initiative for Asthma: Global Strategy for Asthma Management and prevention. 2020. Available from: www.ginasthma.org. 2. Zileuton extended-release [package insert]. Baltimore, MD: Lupin Pharmaceuticals, Inc; August 2020. 3. Zyflo [package insert]. Cary, NC: Chiesi USA, Inc; January 2017.

5 . Revision History

Date Notes

3/23/2021 Modified step to require a failure of one or a contraindication or intolera nce to both step one medications.

Page 791 Zilxi (minocycline)

Prior Authorization Guideline

GL-86025 Zilxi (minocycline)

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 5/1/2021 P&T Approval Date: 12/16/2020 P&T Revision Date: 2/19/2021

1 . Indications Drug Name: Zilxi (minocycline) Rosacea with Inflammatory Lesions Indicated for the treatment of inflammatory lesions of rosacea in adults.

2 . Criteria

Product Name: Zilxi [a] Approval Length 12 month(s) Therapy Stage Initial Authorization Guideline Type Prior Authorization

Page 792

Approval Criteria

1 - Diagnosis of rosacea with inflammatory lesions.

AND

2 - History of failure, contraindication, or intolerance to one of the following topical therapies (document drug, date of trial and reason for therapeutic failure, contraindication, or intolerance):

• azelaic acid (Finacea) • Soolantra

Product Name: Zilxi [a] Approval Length 12 month(s) Therapy Stage Reauthorization Guideline Type Prior Authorization

Approval Criteria

3 . Background

Benefit/Coverage/Program Information

Background:

Page 793 Zilxi is FDA approved for the treatment of inflammatory lesions of rosacea in adults. This formulation of minocycline has not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, Zilxi should be used only as indicated. Members will be required to meet the coverage criteria below.

Zilxi is a tetracycline-class drug indicated for the treatment of inflammatory lesions of rosacea in adults.

Step therapy programs are utilized to encourage use of lower cost alternatives for certain therapeutic classes. This program requires a member to a trial of lower cost rosacea medications before providing coverage for Zilxi.

Additional Clinical Rules:

4 . References

1. Zilxi [package insert]. Bridgewater, NJ: Foamix Pharmaceuticals Inc; May 2020. 2. Rosacea: Diagnosis and Treatment. American Family Physician. 2015 Aug 1;92(3):187- 196 3. Rosacea Medical Management Guidelines. American Acne & Rosacea Society. 2014 Mar;93(3):134-138

5 . Revision History

Date Notes

4/21/2021 02/2021 P&T - Updated criteria to trial of one. Removed metronidazole from step one options.

Page 794 Zomig (zolmitriptan) nasal spray - Step Therapy

Prior Authorization Guideline

GL-85721 Zomig (zolmitriptan) nasal spray - Step Therapy

Formulary UHC Core

Formulary Note

Guideline Note: Effective Date: 6/1/2021 P&T Approval Date: 1/15/2020 P&T Revision Date: 3/17/2021

1 . Indications Drug Name: Zomig (zolmitriptan) nasal spray Migraine Indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older.

2 . Criteria

Product Name: Zomig (zolmitriptan) nasal spray[a] Approval Length 12 month(s) Guideline Type Step Therapy

Page 795 Approval Criteria

1 - History of failure, contraindication, or intolerance to two of the following oral triptans:

• almotriptan (Axert) • eletriptan (Relpax) • frovatriptan (Frova) • naratriptan (Amerge) • rizatriptan (Maxalt/Maxalt MLT) • sumatriptan (Imitrex) • zolmitriptan (Zomig)

AND

2 - History of failure, contraindication, or intolerance to sumatriptan nasal spray (generic Imitrex nasal spray) Notes [a] State mandates may apply. Any federal regulatory requirements an d the member specific benefit plan coverage may also impact coverage criteria. Other policies and utilization management programs may appl y.

3 . Background

Benefit/Coverage/Program Information

Background

Zomig (zolmitriptan) nasal spray is indicated for the acute treatment of migraine with or without aura in adults and pediatric patients 12 years of age and older. Zomig nasal spray is not intended for the prophylactic therapy of migraine attacks or for the treatment of cluster headache.

Step Therapy programs are utilized to encourage the use of lower cost alternatives for certain therapeutic classes. This program requires a member to try generic triptans before providing coverage for Zomig nasal spray.

Additional Clinical Programs • Notwithstanding Coverage Criteria, UnitedHealthcare may approve initial and reauthorization based solely on previous claim/medication history, diagnosis codes (ICD- 10) and/or claim logic. Use of automated approval and re-approval processes varies by

Page 796 program and/or therapeutic class.

4 . References

1. Zomig [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals; May 2019.

5 . Revision History

Date Notes

4/14/2021 Annual Review. No changes.

Page 797