Prior Authorization Medications Requiring Review – Criteria for Use The Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications; this document applies to the Commercial, Triple Tier, Multi-Choice, and Qualified Health Plans formularies. * The Pharmacy Consult Service reviews criteria restrictions for Diabetes, Hepatitis C, Multiple Sclerosis Medications, and PCSK9 Inhibitors

Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Acthar® Corticotropin gel J0800 Medicare Part D Reviewed by the Pharmacy Consult Service for Mutiple Sclerosis indication only Aimovig™ Erenumab-aooe Medicare Part D Ampyra™ Dalfampridine Medicare Part D Reviewed by the Pharmacy Consult Service Arcalyst™ Rilonacept powder for solution J3490 Medicare Part D Aubagio® Teriflunomide Medicare Part D Reviewed by the Pharmacy Consult Service Berinert® Human C1 Inhibitor Medicare Part D Botulinum Toxin: Medicare Part D Botox® (P) Botulinum Toxins Type A J0585 (type Dysport™ (N) Botulinum Toxins Type B A) Myobloc® (N) J0587 (type Xeomin® (N) B) Cerdelga™ Eliglustat Medicare Part D Cholbam® cholic acid Medicare Part D

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 1 of 91

Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Cinqair® Reslizumab Medicare Part B or D

Daklinza® Daclatasvir Medicare Part D Reviewed by the Pharmacy Consult Service

Dipeptidyl peptidase 4 (DPP- Medicare Part D Reviewed by the IV) inhibitors*: Pharmacy Januvia™ Sitagliptin Consult Service Sitagliptin and metformin Janumet™ Linagliptin and metformin Jentadueto® XR Alogliptin Nesina™ Saxagliptin Onglyza™ Alogliptin and metformin Kazano™ Saxagliptin and metformin ER Kombiglyze™ XR Alogliptin and pioglitazone Oseni™ Linagliptin and empagliflozin Glyxambi™ Saxagliptin and dapagliflozin Qtern® Sitagliptin and ertugliflozin Steglujan™

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 2 of 91 Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Dupixent® Dupilumab Medicare Part D Eloctate® Antihemophilic Factor Medicare Part B (Recombinant) Emflaza® Deflazacort Medicare Part D Entyvio® Vedolizumab Medicare Part B or D Enzyme replacement therapy: Velaglucerase Alfa Vpriv® (P) Imiglucerase Cerezyme® (N) Taliglucerase Alfa Elelyso® (N) Epclusa® sofosbuvir and velpatasvir Medicare Part D Reviewed by the Pharmacy Consult Service Exondys 51™ Eteplirsen Fabrazyme Agalsidase Beta Fasenra Benralizumab Medicare Part B or D Firazyr® (N) Icatibant Medicare Part D Gattex® (N) Teduglutide Medicare Part D

Gilenya™ (N) Fingolimod Medicare Part D Reviewed by the Pharmacy Consult Service Glatiramer acetate Medicare Part D Reviewed by the Copaxone® Glatiramer acetate Pharmacy Glatiramer acetate Consult Service GLP-1 Receptor Agonists*: Medicare Part D Reviewed by the Bydureon™ (P) Exenatide Extended-Release Pharmacy Consult Victoza® (N) Liraglutide injection Service Byetta™ (N) Exenatide SQ solution Trulicity (N) Dulaglutide Adlyxin (N) Lixisenatide Soliqua (N) Insulin glargine/lixesenatide Xultophy (N) Insulin degludec/liraglutide Ozempic (N) Semaglutide Growth Hormones: Somatropin (Growth hormone) J2940-J2941 Medicare Part D Omnitrope® (P) injectable Genotropin® (N) Humatrope® (N) Norditropin® (N) Nutropin AQ (N) Saizen® (N)

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 3 of 91 Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Serostim® (N) Zorbtive® (N) Harvoni® Ledipasvir and sofosbuvir Medicare Part D Reviewed by the Pharmacy Consult Service Hemlibra Emicizumab-kxwh Medicare Part D Human C1 Esterase Human C1 Esterase Inhibitor Medicare Part B or Inhibitors: D Cinryze® Haegarda® Hetlioz® Tasimelteon Medicare Part D Hyaluronic Acid Derivatives Hyaluronic Acid Injections J7321-J7322 Medicare Part B (viscosupplements): Supartz® (P) Synvisc® (2) Euflexxa® (N) Hyalgan® (N) Orthovisc® (N) Synvisc-One® (N) Hyzentra Immune globulin (subcutaneous) Medicare Part B Hyqvia Immune globulin and recombinant Medicare Part D or human hyaluronidase B Ilaris® Canakinumab Medicare Part D Ingrezza® Valbenazine Medicare Part D Interleukin (IL) Antagonists: Stelara® (P) Ustekinumab Taltz® Ixekizumab Medicare Part D Tremfya Guselkumab Siliq™ Brodalumab Impavido® Miltefosine Medicare Part D Interferons: Reviewed by the Avonex® (P) Interferon beta-1a Pharmacy Medicare Part D Rebif® (P) Interferon beta-1a Consult Service Plegridy® (N) Peginterferon beta-1a

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 4 of 91 Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Jetrea® Ocriplasmin Juxtapid™ Lomitapide Medicare Part D Kalbitor® Ecallantide Medicare Part D Kalydeco™ Ivacaftor Medicare Part D Keveyis® Dichlorphenamide Medicare Part D Korlym™ Mifepristone Medicare Part D Kuvan™ Sapropterin tablets J3490 Medicare Part D Kynamro™ Mipomersen sodium Medicare Part D Lemtrada® Alemtuzumab Medicare Part B Reviewed by the Pharmacy Consult Service MavyretTM Glaceprevir and Pibrentasvir Medicare Part D Reviewed by the Pharmacy Consult Service Natpara® Parathyroid hormone Medicare Part D Nucala® Mepolizumab Medicare Part B or D Ocrevus™ Ocrelizumab Medicare Part B Reviewed by the Pharmacy Consult Service Olysio® Simeprevir Medicare Part D Reviewed by the Pharmacy Consult Service Orkambi® lumacaftor and ivacaftor Medicare Part D Parathyroid Hormone Medicare Part D Analogs: Forteo® (P) Teriparatide Tymlos® Abaloparatide PCSK-9 Inhibitors: Medicare Part D Reviewed by the Repatha® Evolocumab Pharmacy Praluent® Alirocumab Consult Service Procysbi™ Cysteamine delayed-release Medicare Part D Prolia® Denosumab Medicare Part B or D Provenge® Sipuleucel-T Q2043 Medicare Part B Radicava® Endavarone Medicare Part B or D Ravicti® Glycerol phenylbutyrate Medicare Part D Ruconest® C1 inhibitor (recombinant) Medicare Part B or D Sabril® Vigabatrin Medicare Part D

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 5 of 91 Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Sodium-Glucose Medicare Part D Reviewed by the Cotransporter 2 (SGLT2) Pharmacy Consult Inhibitors*: Service Synjardy™ Empagliflozin and metformin Invokana™ Canagliflozin

Farxiga™ Dapagliflozin Steglatro™ Ertugliflozin Glyxambi™ Empagliflozin and linagliptin Invokamet™ Canagliflozin and metformin Invokamet XR Canagliflozin and metformin

Xigduo XR™ Dapagliflozin and metformin Segluromet™ Ertugliflozin and metformin

Somavert® Pegvisomant Medicare Part D Sovaldi® Sofosbuvir Medicare Part D Reviewed by the Pharmacy Consult Service Spinraza™ Nusinersen Supprelin® LA Histrelin implant J9226 Medicare Part D Symdeko Tezafactor/Ivacaftor Medicare Part D Symlin*® Pramlintide SQ solution J3490 Medicare Part D Reviewed by the Pharmacy Consult Service Tecfidera™ Dimethyl fumarate Medicare Part D Reviewed by the Pharmacy Consult Service Technivie® Ombitasvir/paritaprevir/ ritonavir Medicare Part D Reviewed by the Pharmacy Consult Service

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 6 of 91 Brand Name and/or Generic Name J-Code Medicare Status Notes Therapeutic Class

Tysabri® Natalizumab IV solution J2323 Medicare Part B Reviewed by the Pharmacy Consult Service for Mutiple Sclerosis indication only Viberzi® Eluxadoline Medicare Part D Viekira Pak® Ombitasvir, Paritaprevir, Ritonavir, Medicare Part D Reviewed by the Viekira XR® and Dasabuvir Pharmacy Consult Service VMAT2 Inhibitors: Medicare Part D Austedo® Deutetrabenazine Xenazine® Tetrabenazine Vosevi® Sofosbuvir/velpatasvir/voxilaprevir Medicare Part D Reviewed by the Pharmacy Consult Service Xgeva® Denosumab Medicare Part B Xiaflex™ Collagenase clostridium J0775 Medicare Part B histolyticum injection Xolair® Omalizumab injectable J2357 Medicare Part D Zavesca® Miglustat Zepatier® Elbasvir and Grazoprevir Medicare Part D Reviewed by the Pharmacy Consult Service P- Preferred when criteria met 2-2nd line (if preferred failed) NP- Non-preferred

Last Revised: August 22, 2018 CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Page 7 of 91 Medications Requiring Review – Criteria for Use Drug Prior Authorization Criteria Acthar® Candidates for treatment with Acthar® should meet the following pertinent criteria: (Corticotropin (gel)) Acthar® gel will not be covered in patients with any of the following diagnoses: • Congestive heart failure • Uncontrolled Hypertension • Osteoporosis • History of or presence of peptic ulcer • Primary adrenocortical insufficiency or adrenocortical hyperactivity • Scleroderma • Hypersensitivity to porcine protein • Pancreatitis • Thromboembolic disorder • Ocular herpes simplex • Systemic fungal infections

Criteria for use for diagnosis of infantile spasms: 1. Diagnosis of infantile spasms 2. Less than 2 years of age 3. Prescribed by pediatric neurologist or neurologist

Criteria for use for Nephritic Syndrome: 1. A diagnosis of idiopathic nephritic syndrome 2. Prescriber must be a nephrologist 3. Patient failed to achieve a sustained partial or complete remission of nephritic syndrome after 6 months of therapy with first line therapy (i.e., corticosteroids) AND after 6 months of therapy with second line therapies with demonstrated efficacy (i.e., cyclosporine, tacrolimus, rituximab, and mycophenolate mofetil). Patient is expected to continue therapy for at least 3 months and is able to afford the cost of therapy in order to prevent abrupt discontinuation of therapy.

Criteria for use for FDA-approved corticosteroid responsive conditions: 1. A documented diagnosis of any of the following conditions: a. Rheumatic disorder (psoriatic arthritis, rheumatoid arthritis, ankylosis spondylitis) b. Collagen diseases (SLE, polymyositis) c. Treatment of serum sickness d. Treatment of systematic sarcoidosis e. Ophthalmic-disease (keratitis, iritis, optic neuritis, anterior segment inflammation) f. Dermatological diseases (severe erythema multiforme or Stevens Johnson syndrome) 2. Patient experienced a limited or unsatisfactory response or experienced intolerance to IV or high dose oral steroids

Criteria for use for acute exacerbation of MS: 1. Documented diagnosis of acute exacerbation of multiple sclerosis 2. Prescribed by a neurologist 3. Patient experienced a limited or unsatisfactory response or experienced intolerance to IV or high dose oral steroids

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 8 of 91 Drug Prior Authorization Criteria 4. Patient is currently on an immunomodulator agent for the treatment of multiple sclerosis 5. Patient demonstrates severe exacerbation symptoms (i.e severe weakness, severe loss of vision, severe coordination problems, or severe walking impairment)

Approval period: 6 months for nephritic syndrome and 3 months all other indications

Monitoring: Laboratory monitoring for BMP, blood pressure, pulse, A1C, weight, and TSH, cholesterol (i.e., TC, LDL, HDL and triglycerides) should be completed at baseline and every 3 months for the duration of treatment with Acthar® gel Aimovig Candidates for treatment should meet the following criteria: (Erenumab-aooe) 1. Age 18-65 years AND 2. Documented chronic migraine (>15 days/month or frequent episodic migraine (>8 days/month or >2 disabling migraines/month lasting at least 72 hours) 3. Documented adequate trial of or contraindication to 3 preventative agents, of which 2 must have strong evidence for migraine (e.g. tricyclic antidepressants, beta-blockers, topiramate). a. Adequate trial defined as at least 2 months of a maximally tolerated dose 4. Documented compliance with a headache diary for at least 1 month prior to initiation. 5. If on onabotulinumtoxinA, onabotulinumtoxinA is discontinued and at least 8 weeks has passed since the last dose before beginning this therapy. 6. Prescribed by a Neurologist and/or Pain Management Specialists

Reasons for Non-Coverage:

1. Medication-overuse headache (MOH) based on International Headache Society Classification ICHD-3 (use of triptans, ergotamine, opioids or any combination of these agents for 10 or more days/month for more than 3 months; non-opioid analgesic use for 15 or more days/month for more than 3 months). 2. Opiate or barbiturate use for more than 4 days in the month prior to initiation (this includes tramadol use) 3. Cardiovascular comorbidities (hypertension, cardiovascular diease, etc. 4. Pregnancy or intent to become pregnant 5. History of cluster headache or hemiplegic migraines 6. Elevated LFTs (ALT or AST > 1.5x ULN) or known liver disease 7. BMI < 18 or BMI > 40 8. Pediatric Patients

Initial approval: 3 months. Continued approval: 12 months if the following criteria are met: 1. Documented response of 30% or more reduction in headache days per month OR 50% or more improvement in Migraine Disability Assessment ( MIDAS) scores. 2. Documented adherence to medication, headache diary, and follow-up assessments Criteria for Discontinuation:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 9 of 91 Drug Prior Authorization Criteria • < 30% reduction in headache days per month AND < 50% improvement in MIDAS score after 3 months of treatment. • Lack of sustained effect of the medication • After 9 to 12 months of sustained effect, a trial of discontinuation is recommended. • Intolerance to medication • Non-adherence to medication, headache diary, or follow-up assessments • Pregnancy is diagnosed or woman is breastfeeding Dosage and Administration: For subcutaneous use only. Administer in the abdomen, thigh, or upper arm subcutaneously. • 70 mg by subcutaneous injection once monthly. • Some patients may benefit from a dosage of 140 mg once monthly. The 140 mg dose is administered once monthly as two consecutive subcutaneous injections of 70 mg each. Ampyra™ Ampyra™ extended release tablets should be reserved for treatment intended to improve walking (Dalfampridine) capacity in ambulatory patients with multiple sclerosis (MS). Ampyra™ is symptomatic treatment only and is not disease-modifying.

Candidates for treatment with Ampyra™ should meet the following criteria: 1. Must be prescribed by a neurologist 2. Patient has a confirmed diagnosis of MS. 3. Patient is ambulatory with a baseline 25 foot walk between 8 to 45 seconds a. Documentation of baseline timed 25 foot walk must be submitted by the prescribing physician. 4. Should be used for improvement of speed of ambulation. 5. Physical therapy should be considered and appropriately used before exposing patients to Ampyra™ 6. Patient must have normal renal function (CrCl > 50 ml/min). 7. Patient does not have a history of seizures

Reasons for non-coverage Ampyra™ should NOT be used in patients with any of the following: 1. History of seizures 2. Moderate or severe renal impairment o Moderate renal impairment is defined as creatinine clearance (CrCl) of 30 to 50 mL/min; severe impairment is defined as CrCl of less than 30 mL/min. 3. Non-Ambulatory patients o Ampyra™ clinical trials included only ambulatory patients. Therefore, efficacy and safety have not been tested in non-ambulatory patients. 4. Patients taking any other form of fampridine, such as compounded fampridine (4- aminopyridine or 4-AP) products.

Initial approval period: 2 months • Patient should be evaluated for response 30-60 days after starting the medication • Patient should be instructed that continuation of the drug depends upon being evaluated for response. • Patients should be advised that the reason for this evaluation is to avoid any unnecessary exposure to the drug and its possible risk.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 10 of 91 Drug Prior Authorization Criteria Continued approval: If a response is obtained during the first 2 months that the patient is on the medication, medical records documenting this response, including the walking time for the 25 foot walking test after taking Ampyra™ along with a new prior authorization request should be submitted prior to continued approval being granted. Continued approval period is 12 months.

Response Assessment: A response should become evident within two weeks. Patients should be given a trial of Ampyra™ lasting from 30 to 60 days and then evaluated for response to determine whether to continue the drug. One objective indicator should be used, along with any subjective indicators, to assess response. a. A useful objective assessment is the Timed 25-Foot Walk (T25FW) test. This was the test used in clinical trials qualifying Ampyra™ for approval. i. A baseline should be established at one or more visit after any possible physical therapy and before initiation of Ampyra™. ii. Response to Ampyra™ can then be evaluated with repeat T25FW tests (or equivalent) after 30 to 60 days of drug. b. A subjective assessment should include meaningful improvements in functional parameters or activities of daily living. c. Response to Ampyra™ should be evident within two months. i. Continuation of Ampyra™ in patients who do not have a significant response – a majority of patients in clinical trials – may expose these patients to the risk of seizures without sufficient benefit to justify the risk. ii. Modest improvements in walking speed or function must be considered against the risk of seizures. Dosing: • The maximum dose of Ampyra™ is one 10 mg tablet twice daily, approximately 12 hours apart. Patients should NOT take more than 10 mg every 12 hours. o Patient education must include emphasis on spacing doses approximately 12 hours apart. Irregular dosing intervals will result in uneven blood levels since the drug itself has a relatively short half-life. Uneven drug levels could raise the risk for seizures. o Patients must be cautioned not to “double-up” if they miss a dose and not to take a possible “extra” dose if they have forgotten whether they took a dose. o Patients must be advised to always swallow tablets whole and to never split, crush, chew, or otherwise disrupt the extended-release formulation, since this could lead to uneven blood levels.

Ordering information: Ampyra™ is available through the KP Specialty Pharmacy. Prescribers must complete the KP Specialty Pharmacy Ampyra™ Drug Order Form at http://pharmacy.kp.org/Kp- CMS/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Object=1084&nodeValue=113 and fax it to KP-SP (1-650-301-5790). Arcalyst™ Candidates for treatment with Arcalyst™ should meet ALL the following criteria: (Rilonacept) 1. Diagnosis of cryopyrin-associated periodic syndromes (CAPS) 2. Patient has documented laboratory evidence of a genetic mutation in the Cold-Induced Auto- inflammatory Syndrome 1 (CIAS1- sometimes referred to as the NLRP3).

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 11 of 91 Drug Prior Authorization Criteria 3. There is clinical documentation that the patient is experiencing classic symptoms of CAPS in either criteria below: a. Familial Cold Auto-Inflammatory Syndrome (FCAS) - recurrent episodes of rash, fever/chills, and joint pain following exposure to mild cold environment (e.g. cool breeze, air conditioning). Symptoms generally last for up to 24 hours. b. Muckle-Wells Syndrome (MWS) - chronic fever and rash sometimes exacerbated by generalized cold exposure. Episodes can last up to 2-3 days. 4. There is clinical documentation of significant functional impairment leading to limitations of activities of daily living (ADLs). 5. Failed, intolerant, or allergic to at least one of the following: a. Anakinra (Kineret®) injection b. Canakinumab (Ilaris®) injection

Reasons for non-coverage: • Concurrent use of live vaccines or tumor necrosis factor • Chronic or active infections • Untreated latent tuberculosis • 11 years or younger

Initial approval period: 1 month

Continued approval: 12 months based on physician documentation of disease stability and improvement.

Caution: • Increased risk of malignancies may occur

Monitoring: • Improvement in signs and symptoms of cryopyrin-associated periodic syndromes (ie, fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis) • Lipid profiles; 2 to 3 months after initiation of therapy and periodically

Dosing: • Adult dose: The recommended loading dose is 320 milligrams (mg) subcutaneously (SubQ) as 2 doses of 160 mg at 2 different sites. Followed by 160 mg SubQ once-weekly. Do not administer more than once weekly. • Pediatric dose: The recommended loading dose is 4.4 milligrams/kilogram (mg/kg) subcutaneously (SubQ) (up to a maximum dose of 320 mg) as 1 or 2 injections with a maximum volume of 2 mL. If administered as 2 injections, then administer at 2 different sites. Followed by 2.2 mg/kg (up to a maximum dose of 160 mg) SubQ once weekly. Do not administer more than once weekly Aubagio® Aubagio (teriflunomide) tablets should be reserved for treatment of relapsing forms of multiple (Teriflunomide) sclerosis in patients with moderate disease activity who have contraindications or severe intolerance

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 12 of 91 Drug Prior Authorization Criteria to preferred therapies or have severe injection site reactions not responsive to conservative measures.

Candidates for treatment with Aubagio® should meet ALL the following criteria:

1. Documented diagnosis of relapsing-remitting multiple sclerosis (RRMS) 2. Prescribed by a Neurologist 3. Females of child bearing age (12-50 years of age) should have a baseline negative pregnancy test (within 1 month) AND agreement to be on two forms of reliable birth control (confirm order for IUD or other contraceptive) 4. Documented negative PPD (tuberculin) test 5. Aubagio is being used as monotherapy 6. Documented severe intolerance or relative contraindication to glatiramer acetate (Glatopa or Copaxone®)* AND one interferon therapy (ie. Avonex®, Betaseron®, Extavia®[preferred interferon], Plegridy® or Rebif®* OR 7. Patient is unable to master self-injection technique and lacks a caregiver who can perform injections OR 8. Patient has a history of severe injection site reactions not responsive to conservative measures while on injectable agents for MS (eg: lipoatrophy or skin necrosis) OR 9. Documented concomitant diagnosis of a rheumatologic condition

*NOTE: Injection fatigue or fear of needles is not a reason for intolerance or inadequate response.

Reasons for non-coverage:

Aubagio should NOT be used in patients with ANY of the following:

• Pre-existing hepatic disease or total bilirubin, ALT or AST greater than 2 times the upper limit of normal • Clinical conditions or medications which could potentially affect or worsen hepatic function • Current leflunomide treatment • Pregnancy or lactation

Initial approval period: 1 year

Continued approval for treatment with Aubagio® should meet ALL the following criteria:

1. Documented beneficial effect from therapy during neurology follow up 2. Documented ALT measured at least once during the first 6 months of therapy Consider discontinuation if ALT ≥ 3 x ULN

3. Documented bilirubin and CBC measured within the first 6 months of therapy

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 13 of 91 Drug Prior Authorization Criteria Continued approval: 1 year

Dosage and Administration

• The recommended dose of Aubagio® is 7 mg or 14 mg daily. • Due to the possibility of increased risk of infections, Aubagio should be used as monotherapy and not in combination with other disease-modifying therapies for MS. • Aubagio should be used with caution in patients who are receiving chronic immunosuppressant therapy, other immunomodulatory drugs, or are significantly immunocompromised for any reason.

Ordering information:

Aubagio® is available through the KP Specialty Pharmacy. If approved for coverage, prescribers must complete the KP-SP Aubagio Order Form and fax it to the KP-Specialty Pharmacy (1-650-301-5790).

Berinert® Candidates for treatment with Berinert® should meet ALL the following criteria: (Human C1 Inhibitor) 1. A diagnosis of Type I or Type II hereditary angioedema. 2. Prescriber must be an allergist. 3. Treatment of acute facial or abdominal facial attacks of HAE in adult or adolescent patients 4. Contraindications or inability to tolerate 17α-alkylated androgens (ex. danazol, oxandrolone and stanozolol) (especially in females of child-bearing age, 12-50 years of age), including hirsutism, menstrual irregularities, hepatic dysfunction, undiagnosed vaginal bleeding, porphyria, cardiac or renal disease, depression, muscle cramps and thrombosis. Patients with significant lipid abnormalities might also be considered. 5. Lack of response to currently available therapies such as 17α-alkylated androgens as evidenced by lack of symptom control.

Reasons for non-coverage: • Routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE • Treatment for laryngeal attacks • 12 years of age or younger

Initial Approval: 3 months Subsequent approval will be based on clinical documentation of functional improvement, a decrease in frequency of HAE attack, and an improvement in severity and duration of attacks.

Monitoring: • Symptomatic improvement • Symptoms of hypersensitivity reaction during or after infusion • Signs of thrombosis

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 14 of 91 Drug Prior Authorization Criteria Consider long-term prophylaxis for patients with HAE who experience ≥one severe event per month or who are disabled more than five days per month OR if the patient has a history of previous airway compromise. Options include: 1. 17α-alkylated androgens (danazol, stanozolol if available, and oxandrolone): Generally treatment of choice for long-term preventative treatment. Contraindications include pregnancy, breastfeeding, significantly impaired renal/ hepatic function, etc (refer to package insert for complete list). See Milan or Budapest Protocols for dosing recommendations. Use in children should be undertaken only with great caution. 2. Antifibrinolytics (epsilon aminocaproic acid [Amicar]): Less effective than androgens. Often reserved for patients who do not tolerate or in whom anabolic androgens are contraindicated. 3. Human C1 inhibitor (Cinryze®) replacement: May be necessary in patients in whom androgens are not effective (frequent angioedema attacks), not tolerated or contraindicated. o Human C1 inhibitor prophylaxis is the safest prophylactic agent to use during pregnancy. Botulinum Toxins: Candidates for treatment with Botulinum products should meet ALL the following pertinent criteria:

Preferred: Botulinum products are not interchangeable; potency differences may exist between the products. Botox® Type A Injections Use of Botulinum Toxin for Hyperhidrosis*

Non-preferred: Patient must meet ALL criteria for coverage: Dysport® Type A 1. Receive recommendation from Dermatology after failed medical treatment with Drysol® and Injection Robinul®. 2. Medical complications from hyperhidrosis including skin maceration or dermatitis. Myobloc® Type B 3. No history of neuromuscular disease. Injections 4. No recent infection or malignancy in affected area. 5. No history of hyperthyroidism. Xeomin® Type A Injection Use of Botulinum Toxin for Blepharospasm**

Patient must meet ALL criteria for coverage 1. Diagnosis of bilateral blepharospasm 2. No neuroleptic-induce blepharospasm 3. No known hypersensitivity to botulinum toxins, human serum albumin, or sucrose 4. No treatment with botulinum toxins for any other indications within the past 16 weeks

Use of Botulinum Toxin for Cervical Dystonia

Patient must meet ALL criteria for coverage 1. Diagnosis of primary cervical dystonia (CD) 2. Negative impact on quality of life (pain, motor function impairment, abnormal appearance leading to isolation) *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 15 of 91 Drug Prior Authorization Criteria 3. Muscles involved can be adequately localized to treat with botulinum toxins 4. No history of neuromuscular disease 5. No known hypersensitivity to botulinum toxins, serum albumin, or sucrose 6. No treatment with botulinum toxins for any other indications within the past 16 weeks

Use of Botulinum Toxin for Overactive Bladder 1. Diagnosis of overactive bladder 2. Symptoms of urge urinary incontinence, urgency, and frequency 3. Documented inadequate response to or are intolerant to at least 2 of the following: a. Oxybutynin b. Trospium c. Oxytrol d. Tolterodine

Use of Botulinum Toxin for Urinary Incontinence due to Detrusor Overactivity Associated with a Neurologic Condition 1. Diagnosis of a neurologic condition [e.g., spinal cord injury (SCI), multiple sclerosis (MS)] 2. Symptoms of urge urinary incontinence, urgency, and frequency 3. Documented inadequate response to or are intolerant to at least 2 of the following: a. Oxybutynin b. Trospium c. Oxytrol d. Tolterodine

Use of Botulinum Toxin for Upper Limb Spasticity*

Patient must meet ALL criteria for coverage: 1. Complete neurological evaluation 2. Failure to improve with standard therapy which includes dopaminergic medications (Sinemet®, Artane®), muscle relaxants (Lioresal), and benodiazepines (Valium®). 3. Spasticity in biceps, wrist, or fingers 4. No weakness, atrophy, or infection in the target muscle 5. No hypersensitivity to botulinum toxin or other component of the product 6. No evidence of pre-existing cardiovascular disease or dysphagia

Use of Botulinum Toxin for Cerebral Palsy*

Patient must meet ALL criteria for coverage: 1. Complete neurological evaluation 2. Failure to improve with standard therapy which includes dopaminergic medications (Sinemet®, Artane®), muscle relaxants (Lioresal), and benodiazepines (Valium®). 3. Use limited to the muscles of the arms and legs. 4. No weakness, atrophy, or infection in the target muscle 5. No hypersensitivity to botulinum toxin or other component of the product *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 16 of 91 Drug Prior Authorization Criteria 6. No evidence of pre-existing cardiovascular disease or dysphagia

Initial approval : 6 months

Continued Approval: Up to 4 treatments per 12 months if there is documented evidence of response to therapy

NOTES: • Botulinum Toxin is Pregnancy Category C and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. • The FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of Botulinum toxins types A (Botox®, Botox® Cosmetic) and B (Myobloc®) for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when Botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Consider these adverse events when reviewing requests.

* Consider Botulinum Toxin A (Botox®) before Botulinum Toxin B (Myobloc®) and Botulinum Toxin A (Dysport®).

** Xeomin® is FDA approved for the treatment of blepharospasm in patients previously treated with Botox® and cervical dystonia and should only be covered for FDA-approved indications.

†The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is the most commonly used. It consists of three subscales: severity (range 0-35), disability (range 0-23), and pain (range 0-20), which together add up to the TWSTRS Total score of 0-87 Cerdelga Candidates for treatment with Cerdelga should meet ALL the following criteria: (Eliglustat) 1. Documented diagnosis of Type 1 Gaucher’s Disease 2. Patient is symptomatic (i.e. radiologic evidence of skeletal disease, platelet count <60,000 microL, liver >2.5 times normal size, spleen > 15 times normal size). 3. 18 years of age or older 4. Patient has been evaluated by a Geneticist 5. Patient has been tested using an FDA cleared test to determine the patient’s CYP2D6 genotype 6. Patient’s CYP2D6 genotype has been classified as an extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) 7. Tried and failed or unable to tolerate enzyme replacement therapy (Cerezyme, Vpriv, Elelyso) enzyme replacement therapy for at least 6 months

Initial approval period: 6 months

Continued approval: 12 months if patient is responding to treatment (improving platelet count, decreased hepatomegaly and splenomegaly) *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 17 of 91 Drug Prior Authorization Criteria

Dosing and Administration: • CYP2D6 EMs or IMs: 84 mg orally twice daily • CYP2D6 PMs: 84 mg orally once daily • Swallow capsules whole, do not crush, dissolve or open capsules • Avoid eating grapefruit or drinking grapefruit juice

Ordering information: Cerdelga is available through the KP Specialty Pharmacy. If approved for coverage, prescribers must complete the KP-SP Cerdelga Order Form and fax it to the KP-Specialty Pharmacy (1-650-301-5790). Cholbam Candidates for treatment with Cholbam should meet ALL of the following criteria: (cholic acid) 1. Ordering providers are restricted to: pediatric gastroenterology and adult hepatology/gastroenterology 2. Must have a diagnosis of bile acid synthesis disorder A) Bile acid disorders due to single enzyme defects (SEDs) OR B) Adjunctive treatment of peroxisomal disorders (PDs) including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption 3. Must provide baseline liver function tests

Reasons for non-coverage: 1. Patients with extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders

Initial approval period: 3 months

Continued approval: Every 3 months for the first year, then every 6 months thereafter based on: 1. Adherence to Cholbam (>80%) and 2. Documented beneficial effect from therapy including all of the following: a. Body weight increased by 10% or is stable at >50th percentile b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <50U/L or baseline levels reduced by 80% c. Total bilirubin level reduced to <1mg/dL d. Must not have evidence of cholestasis on liver biopsy

Monitoring: • Every month for the first 3 months, every 3 months for the next 9 months, and every 6 months during the next three years, and annually thereafter: o Bilirubin o ALT/AST/GGT Liver function tests o INR

Reasons for Discontinuation: • Liver function does not improve within 3 months of starting treatment • Complete biliary obstruction develops • Persistent clinical or laboratory indicators of worsening liver function or cholestasis *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 18 of 91 Drug Prior Authorization Criteria

Ordering information: Cholbam is available through the Cholbam Total Care Hub. If approved for coverage, prescribers must complete the Patient Enrollment Form for Cholbam Total Care Hub and fax it to 877-473-3171. Candidates for Cinqair® should meet ALL of the following criteria: Cinqair® (Reslizumab) 1. Documented failure of, contraindication or intolerance to mepolizumab (Nucala) [KPGA’s preferred interleukin-5 antagonist] 2. Prescribed by a pulmonologist or allergy specialist 3. 18 years of age or older 4. Has a diagnosis of severe asthma with an eosinophilic phenotype: a. Documented blood eosinophil count of > 400 cells/µl. 5. Uncontrolled asthma* despite an aggressive drug therapy regimen including: a. High-dose inhaled corticosteroid (ICS), plus a long-acting beta-agonist (LABA)—e.g. fluticasone 500 mcg/salmeterol 50 mcg (Advair Diskus) 1 puff twice daily WITH b. Daily use of oral corticosteroids (OCS)—e.g. prednisone 5 – 20 mg daily 6. NOTE: Patients who are not on daily OCS but who otherwise meet the above criteria and who have had frequent and/or severe exacerbations in the past 12 months requiring systemic corticosteroids for > 3 days can be considered for reslizumab (Cinqair). 7. NOT being used for the treatment of other eosinophilic conditions such as hypereosinophilic syndromes (e.g. Churg-Strauss, EGPA), neoplastic disease, or parasitic disease. 8. NOT being treated for relief of acute bronchospasm or status asthmaticus. 9. NOT currently receiving another monoclonal antibody for the treatment of asthma—e.g. omalizumab (Xolair), mepolizumab (Nucala), benralizumab (Fasenra). 10. Does NOT have any current diagnosis of cancer or history of cancer in remission for less than 12 months prior to starting therapy.

*Indicators of uncontrolled asthma: Two or more exacerbations in the past 12 months requiring systemic corticosteroids for > 3 days, serious exacerbations, at least one hospitalization, ICU stay or mechanical ventilation in the past 12 months, or Asthma control test (ACT) is consistently < 20.

Initial Approval: 3 months

Continued Approval: 12 months if the patient has experienced any of the following: 1. Member has experienced a reduction in asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath 2. Member has experienced a decrease in administration of rescue medication, albuterol (e.g. Ventolin, albuterol nebulizing solution) 3. Member has experienced a decrease in exacerbation frequency (no increase in ICS dose or OCS dose) 4. Member has experienced an increase in predicted FEV1 from the pretreatment baseline 5. Member has an objective improvement in quality of life: Asthma Control Test (ACT) 6. NOTE: Do not approve if: a. Member has documented hypersensitivity reactions related to Cinqair administration (e.g. anaphylaxis, angioedema, shortness of breath, hypotension, itching, rash) b. Member has documented diagnosis of malignancy

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 19 of 91 Drug Prior Authorization Criteria

Dosage and administration: The recommended dose is 3 mg/kg every 4 weeks as an intravenous infusion over 20-50 minutes Should be prepared and administered by a healthcare professional Monitoring: 1. Patients should be observed for hypersensitivity reactions during the infusion and for approximately 60 minutes after administration for signs/symptoms of anaphylaxis 2. FEV1, peak flow, and/or other pulmonary function tests 3. Frequency of administration of rescue medication (short-acting beta2-agonist, albuterol) 4. Asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath 5. Frequency of exacerbation Daklinza® Daklinza is a non-preferred treatment agent at Kaiser Permanente. Please refer all requests to (Daclatasvir) internal KP Hepatology or Infectious Disease for discussion. DPP-4 inhibitors: Non-preferred DPP-4 inhibitors: Only to be used when the preferred DPP-4 inhibitor (Tradjenta™) and alogliption (Nesina) have failed. Nesina™ For non-preferred combination product: (Alogliptin) 1. Patient must meet criteria for DPP-4 inhibitor (below) AND 2. Separate prescriptions are required for ingredients in non-preferred combination products

Januvia™ ** DPP-4 inhibitors are not substitutes for insulin in patients whose diabetes control may benefit from (Sitagliptin) insulin therapy.

Onglyza™ ***Note: In patients with clinical atherosclerotic cardiovascular disease (ASCVD) (includes acute (Saxagliptin) coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, carotid stenosis ≥50%, or symptomatic peripheral arterial disease Non-Covered presumed to be of atherosclerotic origin) consider the use of empagliflozin (Jardiance) if additional medications are needed to achieve glucose control. combination products The non-preferred DPP-4 inhibitor will be covered for current KP new start members who meet ALL (separate of the following criteria: prescriptions required for 1. Documented diagnosis of type 2 diabetes mellitus in patients > 18 years of age ingredients in 2. A1c within 1% of goal in the past 3 months. combination a. A1c goal < 7% for patients 18-64 years of age products): b. A1c goal of at least < 8% is acceptable for patients > 65 years of age, or for patients 18-64 years with a history of dementia, blindness, lower extremity Kazano™ amputation, CKD 4/5, ESRD, cardiomyopathy/CHF, or history of cardiovascular (Alogliptin and disease (MI, CABG, percutaneous coronary intervention, angina, metformin) thoracoabdominal aneurysm, carotid stenosis, renal atherosclerosis, peripheral vascular disease). Oseni™ 3. Failed to obtain adequate glycemic control on combination therapy with: (Alogliptin and a. Metformin dose at least 1000mg per day (adherence > 80% for 3 months) unless pioglitazone) patient is not a candidate for metformin AND *Note: If GI intolerance on metformin IR, must complete a trial metformin Kombiglyze™ XR SR 500mg 1 tab po daily for 7 days then titrate to metformin SR 500mg 1 (Saxagliptin and tab po bid as tolerated.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 20 of 91 Drug Prior Authorization Criteria metformin b. Sulfonylurea (adherence > 80% for 3 months) unless the patient is not a extended-release) candidate for sulfonylurea therapy or the patient is already on multiple daily insulin injections (i.e prandial insulin) AND Janumet™ c. Titration of insulin: For non-obese patients (BMI ≤29) an insulin dose of 0.4-0.6 (Sitagliptin and units/kg/day and for obese patients (BMI ≥30) an insulin dose of 0.8 – 1.2 metformin) units/kg/day) OR i. The DPP-4 inhibitor may be initiated prior to insulin trial if patient meets Glyxambi ONE of the following criteria: (empagliflozin and 1. Commercial driver’s licenses OR linagliptin) 2. Significant weight gain (≥ 5% increase in body weight after 6 months of starting a diabetes agent) 4. Patient is not currently on an agent in any of the following classes: GLP-1 RAs, SGLT2 QTERN® inhibitor, and DPP-4 inhibitors (saxagliptin and 5. Documented trial, intolerance or contraindication to Tradjenta, if request is for non-preferred dapagliflozin) DPP-4 inhibitor

Steglujan Initial approval period: 5 months. Patient must obtain HbgA1c after 3 months of initiating therapy (sitagliptin and (this lab should be ordered when initiating therapy). ertugliflozin) Continued approval: 1 year, based on: Jentadueto XR 1. Adherence (> 80%) to diabetic regimen AND (linagliptin and 2. Documented HgbA1c lowering of 0.5% from initial A1c to result in a sustained A1c of ≤7.9% (must be performed within the past 3-6 months). metformin) Members new to KP already taking a non-preferred DPP-4 inhibitor initiated prior to enrollment: Will be covered for those who meet ALL the following criteria: 1. Documented diagnosis of type 2 diabetes mellitus AND 2. Metformin dose at least 1000mg per day unless patient is not a candidate for metformin AND Note: If GI intolerance on metformin IR, must complete a trial metformin SR 500mg 1 tab po daily for 7 days then titrate to metformin SR 500mg 1 tab po bid as tolerated 3. Adherence to sulfonylurea (unless patient is not a candidate or cannot tolerate) AND 4. A1c < 8% within 30 days AND 5. Patient is not currently on an agent in any of the following classes: GLP-1 RAs, SGLT2 inhibitor, and DPP-4 inhibitors AND 6. Documented trial, intolerance or contraindication to Tradjenta, if request is for non-preferred DPP-4 inhibitor

Continued Approval: 1 year based on: 1. Adherence (> 80%) to diabetic regimen AND 2. A1c of ≤8% (must be performed within the past 3-6 months). AND

Reasons for non-coverage: 1. Type 1 diabetes mellitus 2. Treatment of diabetic ketoacidosis 3. Pediatric patients (<18 years old) 4. Severe hepatic insufficiency (Child-Pugh score >9) *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 21 of 91 Drug Prior Authorization Criteria

Dupixent® Candidates for treatment with Dupixent® should meet ALL the following criteria:

(Dupilumab) 1. Documented moderate-to-severe atopic dermatitis 2. Prescribed by a dermatologist or an allergist 3. Patient is 18 year of age or older 4. Documented inadequate response, intolerance or contraindication to BOTH of the following topical therapies: a. Medium or very high potency topical corticosteroid [listed from lower to higher potency in each category] Medium Potency High and Very High Potency Triamcinolone acet 0.1%, 0.025% O, C Betameth diprop aug 0.05% C Betamethasone val 0.1% C Fluocinonide 0.05% O, C, G Mometasone 0.1% O, C Fluocinonoide-emollient 0.05% C Triamcinolone acet 0.5% C Desoximetasone 0.25% C Betamethasone diprop 0.05% C Betamethasone diprop aug 0.05% O, G Betamethasone val 0.1% L Clobetasol 0.05% O, C O = oint, C = cream, G = gel, L = lotion b. Topical calcineurin inhibitors [Pimecrolimus (Elidel) or tacrolimus (Protopic)]

5. Documented inadequate response, intolerance or contraindication to ONE of the following systemic therapies: a. Corticosteroids, cyclosporine, azathioprine, or methotrexate 6. Patient is NOT receiving Dupixent in combination with another biologic medication [e.g. omalizumab (Xolair), rituximab (Rituxan), etanercept (Enbrel), Infliximab (Remicade)] 7. NOT given concurrently with live vaccines

Initial Approval: 4 Months

Continued Approval: 12 months if patient has documented a clinically significant benefit from medication as defined by the Provider.

Dosage and Administration The recommended dose is an initial dose of 600 mg (two 300 mg injections in different injection sites), followed by 300 mg given every other week. Eloctate Candidates for treatment with Eloctate should meet ALL the following criteria: (Antihemophilic 1. Documented diagnosis of Hemophilia A (<1% endogenous Factor VIII activity) Factor 2. Being use for one of the following: (Recombinant), Fc a) Control and prevention of bleeding episodes Fusion Protein) b) Perioperative management c) Routine prophylaxis to prevent or reduce the frequency of bleeding episodes 3. Tried and failed or unable to tolerate TWO of the following: a) Advate b) Kogenate FS *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 22 of 91 Drug Prior Authorization Criteria c) Xyntha d) Helixate FS

Initial approval period: 12 months

Dosing and Administration: • One unit per kilogram body weight will raise the Factor VIII level by 2% international units per deciliter [IU/dL]. Each vial of Eloctate is labeled with the amount of recombinant factor VIII in IU. • Dosing formula for bleeding episodes and perioperative management: o Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg) OR o Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL) • Dosing for routine prophylaxis is: 50 IU/kg every 4 days; it may be adjusted based on patient response with dosing in the range of 25-65 IU/kg at 3-5 day Emflaza® Candidates for treatment should meet all the following criteria: (Deflazacort) 1. Documented diagnosis of Duchenne muscular dystrophy (DMD) 2. Prescribed by a pediatric or adult neurologist with neuromuscular expertise 3. Patient is at least 5 years of age or older 4. Patient had onset of weakness before 5 years of age 5. Patient has tried prednisone for at least 12 months AND 6. Documented clinically significant weight gain, defined as crossing at least two stanines on the weight growth chart during the first 2 years of prednisone use (new weight gain after several years of prednisone use is likely due to multiple factors such as inactivity and persistence of appetite).

Reasons for non-coverage: • No prior history of prednisone use

Initial Approval: 6 months

Continued Approval: 6 months if there is documented adherence to follow-up assessments (Weight, BMI, Blood pressure and HbA1c)

Criteria for Discontinuation: • Non-adherence to follow-up assessments • Increased stanine on weight growth chart persists or worsens after one year on deflazacort • Intolerance due to adverse effects

Dosage and Administration The recommended once-daily dosage is approximately 0.9 mg/kg/day administered orally. Discontinue deflazacort gradually when administered for more than a few days.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 23 of 91 Drug Prior Authorization Criteria Entyvio® Candidates for treatment with Entyvio® should meet ALL the following criteria: (Vedolizumab) 1. Prescribed by a gastroenterologist 2. Documented diagnosis of moderate to severe active ulcerative colitis or Crohn’s disease 3. Inadequate response or an inability to tolerate ONE conventional therapy (i.e. sulfasalazine, mesalamine, azathioprine, or 6-mercaptopurine) 4. Inadequate response or an inability to tolerate corticosteroids (i.e. prednisone, methylprednisolone, budesonide) 5. Inadequate response or an inability to tolerate ONE TNF-α inhibitor (i.e. infliximab (Remicade), adalimumab (Humira)) 6. Entyvio® should not be used concomitantly with a TNF- α inhibitor 7. Patient has documented negative test for tuberculosis within the past 12 months

Reasons for non-coverage: Entyvio® should NOT be used in patients with any of the following: • Patients under 18 years old • Presence of active severe infection or history of recurrent severe infections • Signs and symptoms of liver injury such as jaundice, dark urine, elevated liver transaminases, right upper abdominal discomfort, fatigue and anorexia. • Diagnosis or signs or symptoms of progressive multifocal leukoencephalopathy (PML)

Initial approval period: 14 weeks (Infusions at 0, 2, 6, and 14 weeks)

Continued approval for treatment with Entyvio® should meet ALL the following criteria: 1. Review of compliance to Entyvio® 2. Documented beneficial effect from therapy such as reduction in signs or symptoms of disease

Continued approval: 1 year Dosage and Administration • The recommended dose of Entyvio® for ulcerative colitis and Crohn’s disease is 300 mg infused intravenously (IV) over 30 minutes at 0, 2, and 6 weeks, then 300 mg IV every 8 weeks thereafter.

Monitoring 1. All patients should be monitored for hypersensitivity reactions during infusion until it is complete. o Stop the infusion and consult the physician immediately if signs or symptoms related to a hypersensitivity reaction are seen. These may include anaphylaxis, dyspnea, bronchospasm, urticarial, flushing, rash, or increased blood pressure and heart rate. Symptom onset could occur during the infusion, immediately after the infusion or up to several hours after the infusion. 2. Patients should be monitored for signs and symptoms of severe infections like tuberculosis, sepsis and anal abscess. 3. Monitor patients for signs and symptoms of liver injury such as elevated liver transaminases

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 24 of 91 Drug Prior Authorization Criteria and bilirubin, jaundice, right upper abdominal discomfort, dark urine, anorexia or fatigue. 4. Patients should be monitored for signs and symptoms of PML including progressive unilateral weakness, vision disturbance, changes in thinking and memory, confusion and personality changes. Enzyme Candidates for treatment should meet ALL the following criteria: replacement therapy 1. Documented diagnosis of Type 1 Gaucher’s Disease 2. Patient is symptomatic (i.e. radiologic evidence of skeletal disease, platelet count <60,000 microL, liver >2.5 times normal size, spleen > 15 times normal size) Preferred: 3. Patient has been evaluated by a Geneticist Vpriv (Velaglucerase Initial approval period: 6 months alfa) Continued approval: 12 months if patient is responding to treatment (improving platelet count, Non-Preferred: decreased hepatomegaly and splenomegaly) Cerezyme (Imiglucerase) Monitoring: • Disease monitoring: CBC, liver enzymes, IgG antibodies; MRI, CT, or US of liver and spleen; bone density studies; monitor antibodies in those patients who developed antibodies to Elelyso other enzyme replacement therapies (Taliglucerase alfa) Dosing and Administration: Cerezyme • Administered by intravenous infusion over 1-2 hours. • Dosage should be individualized to each patient. Initial dosages range from 2.5 U/kg of body weight 3 times a week to 60 U/kg once every 2 weeks. Vpriv • Patients Naïve to Enzyme Replacement Therapy: 60 Units/kg • Patients being treated with stable imiglucerase dosages for Gaucher disease: Can switch to VPRIV at previous imiglucerase dose two weeks after last imiglucerase dose Elelyso • Treatment-naïve adult and pediatric patients 4 years of age and older: 60 units/kg administered every other week as a 60 to 120 minute intravenous infusion • Patients switching from imiglucerase: Begin treatment with Elelyso at the same unit/kg dose as the patient's previous imiglucerase dose. Physicians can make dosage adjustments based on achievement and maintenance of each patient's therapeutic goals Epclusa® Candidates for Epclusa should meet ALL the following criteria: (Sofosbuvir/velpat asvir) 1. Is the medication prescribed by a Gastroenterologist or Infectious Disease specialist? If yes, go to #2 If No, patient does NOT meet criteria for Epclusa; go to #5

2. Does the patient have a documented Hepatitis C Virus RNA PCR quantitative in previous 6 months? If yes, go to # 3 If No, patient does NOT meet criteria for Epclusa: patient needs updated viral load, go to #5

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 25 of 91 Drug Prior Authorization Criteria 3. Does patient meet criteria for 8-week Harvoni treatment? o Genotype 1 AND o Treatment-naïve AND o Baseline Viral Load < 6 million IU/ml AND o Non-Cirrhotic AND o Not co-infected with HIV If Yes, patient does NOT meet criteria for Epclusa; Go to #5 If No, go to #4

4. Does the patient have an eGFR > 30 ml/min/1.73 m2 If yes, Patient meets criteria for Epclusa for 12 weeks If No, Go to # 5

5. Has patient been reviewed by the KP Hepatology Clinic OR KP Infectious Disease service? If yes, continue with approval If No, please contact Lisa Woolard, PharmD at 770-677-5869

Approval: 12 weeks total duration

GI or ID specialist will call after start of therapy if patient needs to stop or change therapy:

Dosage and Administration: • One tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily with or without food.

Exondys 51 Candidates for treatment with Exondys 51 should meet ALL the following criteria:

(Eteplirsen) 8. Treatment of Duchenne muscular dystrophy (DMD) with confirmed deletion/mutation amenable to exon 51 skipping (Confirmation of appropriate testing by a geneticist is required) 9. Prescribed by Pediatric Neurology or Adult Neurology with neuromuscular expertise. 10. Must be at least 4 years old 11. Must be Ambulatory; cane or walker use acceptable, but No wheelchair dependency 12. Documentation in Medical Record: Minimum distance for unassisted 6- minute walk test (6MWT): 180 m 13. Must be on a stable dose of glucocorticoids for at least 6 months 14. Prior to treatment initiation, ALL patient must be reviewed by an Interregional Consultative Physician Panel a. Route to Pharmacy Consult Service for review by an interregional Consultative Physician panel

Reasons for Non-Coverage: • Non-ambulatory • Ambulatory with some level of wheelchair dependency

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 26 of 91 Drug Prior Authorization Criteria Initial Approval: 6 months

Continued Approval: 6 months (MUST be reassessed every 6 months by Consultative Physician Panel to determine need for continued therapy).

Criteria for Discontinuation: If patient does NOT meet ALL of the following functional criteria: • Ambulation test: Limited home level or greater, AND • Sit to Stand Test: Moderate assist or Independent, AND • No ventilator support (excluding use of nocturnal CPAP)

Dosing: 30 mg/kg weekly as a 35 to 60- minute intravenous infusion, diluted in 100-150 ml 0.9% sodium chloride injection, USP. Fabrazyme Candidates for treatment with Fabrazyme should meet ALL the following criteria: (Agalsidase beta) 1. Patient age >8 years old 2. Documented diagnosis of Fabry disease confirmed by one of the following: a) α-galactosidase activity level < 1.5 nmol/hr/ml in plasma; OR b) β-galactosidase activity level < 4 nmol/hr/mg in leukocytes 3. Additional labs (prior to starting Fabrazyme): a) Globotriaosylceramide (GL-3) concentrations in plasma > 5ng/mcL b) SCr < 2.5 mg/dL and no history of renal dialysis or transplantation

Initial approval period: 6 months

Continued approval: 12 months

Dosing and Administration: • 1 mg/kg body weight given every two weeks as an IV infusion o Initial IV infusion rate should be no more than 0.25mg/min (15 mg/hr) and may be slowed if an infusion-associated reaction occurs o After patient tolerance to the infusion is well established, the infusion rate may be increased in increments of 0.05-0.08 mg/min (3-5mg/hr) each subsequent infusion • Patients should receive antipyretics prior to infusion Fasenra® Candidates for Fasenra® should meet ALL of the following criteria: (Benralizumab) 1. Documented failure of, contraindication, or intolerance to mepolizumab (Nucala) [KPGA’s preferred interleukin-5 antagonist] 2. Prescribed by a pulmonologist or allergy specialist 3. 18 years of age or older 4. Has a diagnosis of severe asthma with an eosinophilic phenotype: a. Documented blood eosinophil count of: i. ≥ 300 cells/mm3 at therapy initiation OR ii. ≥ 150 cells/mm3 if on oral corticosteroids (OCS) 5. Uncontrolled asthma* despite an aggressive drug therapy regimen including: a. High-dose inhaled corticosteroid (ICS), plus a long-acting beta-agonist (LABA)—e.g. fluticasone 500 mcg/salmeterol 50 mcg (Advair Diskus) 1 puff twice daily WITH b. Daily use of OCS—e.g. prednisone 5 – 20 mg daily 6. NOTE: Patients who are not on daily OCS but who otherwise meet the above criteria and who

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 27 of 91 Drug Prior Authorization Criteria have had frequent and/or severe exacerbations in the past 12 months requiring systemic corticosteroids for > 3 days can be considered for benralizumab (Fasenra). 7. NOT being used for the treatment of other eosinophilic conditions such as hypereosinophilic syndromes (e.g. Churg-Strauss, EGPA), neoplastic disease, or parasitic disease. 8. NOT being treated for relief of acute bronchospasm or status asthmaticus. 9. NOT currently receiving another monoclonal antibody for the treatment of asthma—e.g. omalizumab (Xolair), mepolizumab (Nucala), reslizumab (Cinqair).

*Indicators of uncontrolled asthma: Two or more exacerbations in the past 12 months requiring systemic corticosteroids for > 3 days, serious exacerbations, at least one hospitalization, ICU stay or mechanical ventilation in the past 12 months, or Asthma control test (ACT) is consistently < 20.

Initial Approval: 3 months

Continued Approval: 12 months if the patient has experienced any of the following: • Member has experienced a reduction in asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath • Member has experienced a decrease in administration of rescue medication, albuterol (e.g. Ventolin, albuterol nebulizing solution) • Member has experienced a decrease in exacerbation frequency (no increase in ICS dose or OCS dose) • Member has experienced an increase in predicted FEV1 from the pretreatment baseline • Member has an objective improvement in quality of life: Asthma Control Test (ACT) • NOTE: Do not approve if member has documented hypersensitivity reactions related to Fasenra administration (e.g. anaphylaxis, angioedema, shortness of breath, hypotension, itching, rash)

Dosage and administration: • The recommended dose is 30 mg administered by subcutaneous injection once every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter. • Should be reconstituted and administered by a healthcare professional

Monitoring: • Monitor the patient for hypersensitivity reactions approximately 60 minutes after the administration of each dose. • FEV1, peak flow, and/or other pulmonary function tests • Frequency of administration of rescue medication (short-acting beta2-agonist, albuterol) • Asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath • Frequency of exacerbation Firazyr® Candidates for treatment with Firazyr® should meet ALL the following criteria: (Icatibant) 1. A diagnosis of Type I or Type II hereditary angioedema. 2. Prescriber must be an allergist. 3. Treatment of acute facial or abdominal facial attacks of HAE in adult or adolescent patients

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 28 of 91 Drug Prior Authorization Criteria 4. Contraindications or inability to tolerate 17α-alkylated androgens (especially in females of child-bearing age), including hirsutism, menstrual irregularities, hepatic dysfunction, undiagnosed vaginal bleeding, porphyria, cardiac or renal disease, depression, muscle cramps and thrombosis. Patients with significant lipid abnormalities might also be considered. 5. Lack of response to currently available therapies such as 17α-alkylated androgens as evidenced by lack of symptom control.

Reasons for non-coverage: • Routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE • 18 years of age or younger

Initial Approval: 3 months Subsequent approval will be based on clinical documentation of functional improvement, a decrease in frequency of HAE attack, and an improvement in severity and duration of attacks.

Monitoring: • Symptomatic improvement • Patients with laryngeal attacks should seek medical attention to assure that airway obstruction in resolved.

Consider long-term prophylaxis for patients with HAE who experience ≥one severe event per month or who are disabled more than five days per month OR if the patient has a history of previous airway compromise. Options include: 1. 17α-alkylated androgens (danazol, stanozolol if available, and oxandrolone): Generally treatment of choice for long-term preventative treatment. Contraindications include pregnancy, breastfeeding, significantly impaired renal/ hepatic function, etc (refer to package insert for complete list). See Milan or Budapest Protocols for dosing recommendations. Use in children should be undertaken only with great caution. 2. Antifibrinolytics (epsilon aminocaproic acid [Amicar®]): Less effective than androgens. Often reserved for patients who do not tolerate or in whom anabolic androgens are contraindicated. 3. Human C1 inhibitor (Cinryze®) replacement: May be necessary in patients in whom androgens are not effective (frequent angioedema attacks), not tolerated or contraindicated. o Human C1 inhibitor prophylaxis is the safest prophylactic agent to use during pregnancy. Gattex® Candidates for treatment with Gattex® should meet ALL the following criteria: (Teduglutide) 1. Diagnosis of short bowel syndrome (SBS) 2. Dependent on parenteral nutrition (PN) and/or intravenous (IV) fluids continuously for at least 12 months 3. Prescribed by a gastroenterologist who is a certified REMS provider *NOTE: For more information and to enroll, please go to the following site: http://www.gattexrems.com/ *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 29 of 91 Drug Prior Authorization Criteria 4. 18 years or age or older 5. Colonoscopy performed within the last 6 months 6. Serum bilirubin, alkaline phosphatase, lipase and amylase levels drawn within the last 6 months

Initial approval period: 1 year

Continued approval: 1 year, based on review of compliance to therapy and documented beneficial effect from therapy. Patient must also have documented colonoscopy 1 year after therapy with Gattex®.

Dosing and Administration: • SubQ: 0.05 mg/kg once daily

Monitoring: • Serum bilirubin, alkaline phosphatase, lipase and amylase (baseline [within 6 months prior to initiation] and every 6 months thereafter) • Colonoscopy of entire colon and removal of polyps (baseline [within 6 months prior to initiation], 1 year, and ≤5 years thereafter) • Monitor fluid status in patients with cardiovascular disease; signs/symptoms of intestinal obstruction; signs/symptoms suggestive of gall bladder disease or pancreatitis

Ordering information Gattex® is available through the KP Specialty Pharmacy. Prescribers must complete the KP Specialty Pharmacy Kalydeco™ Drug Order Form at http://pharmacyprod.appl.kp.org/KP- CMS/California/DrugInformation/ViewDrugShortageDNMgmtCA.aspx?I32Object=1599&nod eValue=112 and fax it to KP-Specialty Pharmacy (1-650-301-5790) Gilenya™ Gilenya should be reserved for treatment of patients with relapsing forms of multiple sclerosis (Fingolimod) exhibiting high-disease activity or prognostic factors for early progression to secondary progressive multiple sclerosis.

Candidates for treatment with Gilenya™ should meet ALL the following criteria:

1. Documented diagnosis of relapsing-remitting multiple sclerosis (RRMS) or progressive- relapsing multiple sclerosis (PRMS) 2. Prescribed by a neurologist 3. Gilenya is prescribed for use as monotherapy for treatment of MS 4. Documented baseline CBC with differential, ophthalmologic exam, LFT, serum bilirubin and EKG 5. For females of child bearing age (12-50 years of age), a baseline negative pregnancy test within the past month AND either a prescription for birth control (IUD or other contraceptive) or documentation of the patient declining contraception and being counseled of the potential risk of pregnancy. 6. Documented inadequate response, intolerance or contraindication to glatiramer acetate

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 30 of 91 Drug Prior Authorization Criteria (Glatopa or Copaxone®)* AND ONE interferon therapy (ie. Avonex®, Betaseron®, Extavia® [preferred interferon] , Plegridy® or Rebif®)* OR 7. Documented evidence of at least one high-risk feature for early progression to secondary- progressive MS (see Table 1)

*NOTE: Injection fatigue or fear of needles are not reasons for intolerance or inadequate response.

Table 1: High-risk features for early progression

History of MS relapse with Lesion load Duration Symptom type Timing / frequency ≥ 30 days and Sphincter OR ≥ 3 relapses in the After 1 yr of therapy, significant functional Motor OR first 2 years after ≥ 3 new or enlarging limitations besides Cerebellar (ataxia or diagnosis OR T2 lesions, ongoing sensory tremor) Average of ≥ 1 continued gad+ symptoms relapse/ year over 2 lesions, or diffusion- to 3 years OR restricted imaging After 6 months of lesions over a 1 yr new therapy, period OR relapse in the next 6 ≥ 5 lesions over 2 months years OR ≥ 1 cord lesion

Reasons for non-coverage:

Gilenya should NOT be used in patients with ANY of the following:

• Unstable angina within the last 6 months • Concomitant Class Ia or Class III anti-arrhythmic drugs (beta-blockers, diltiazem, verapamil, quinidine, disopyramide, procainamide, amiodarone, dofetilide, ibutilide, dronedarone, sotalol) • Heart failure, class III/IV within the last 6 months • Decompensated heart failure requiring hospitalization within the last 6 months • Mobitz type II second-degree or third-degree atrioventricular block (history or current), unless the patient has a functional pacemaker • Myocardial infarction within the last 6 months • QTc interval at baseline 500 milliseconds or greater • Sick-sinus syndrome (history or current), unless the patient has a functional pacemaker • Heart rate less than 55 bpm • Irregular heartbeat • Stroke within the last 6 months • TIA within the last 6 months • Opportunistic infection *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 31 of 91 Drug Prior Authorization Criteria • Macular edema or significant risk factors for macular edema (diabetes or uveitis), unless documentation that benefit of Gilenya outweighs risk • Pregnancy or lactation

Initial approval period: 1 year

Continued approval for treatment with Gilenya should meet ALL the following criteria:

1. Documented beneficial effect from therapy during neurology follow up 2. Documentation of at least one examination of the fundus of the eye or optical coherence tomography imaging test after therapy initiation (recommended 3-4 months after therapy initiation) Continued approval: 1 year

Dosage and Administration

• Gilenya is dosed at 0.5 mg orally once daily, with or without food. Doses higher than 0.5 mg daily are associated with minimal benefit and a higher risk of adverse events. • Gilenya should be used with caution in patients who are receiving chronic immunosuppressant therapy, other immunomodulatory drugs, or are significantly immunocompromised for any reason.

Glatiramer Glatiramer 40 mg/ml will be covered for members who meet ALL of the following criteria: acetate: 1. Documented diagnosis of relapsing multiple sclerosis AND Glatiramer 40 2. Glatiramer acetate is prescribed by a neurologist AND mg/ml [Preferred] 3. Glatiramer acetate is to be used as monotherapy disease-modifying treatment of MS AND Copaxone 40 4. Documented history of persistent or severe injection site reactions not responsive to mg/ml conservative measures (eg: lipoatrophy or skin necrosis) while on glatiramer acetate 20 mg Copaxone 20 daily injections or another injectable medication AND mg/ml 5. If the physician's request for coverage of a non-preferred glatiramer acetate is based upon the physician's and/or member's unwillingness to change to a preferred alternative, the request will be denied unless the member meets the criteria. 6. If brand name Copaxone, must have a documented allergy/intolerance to the components of the generic.

Initial approval period: 1 year

Continued approval for treatment with glatiramer should meet ALL the following criteria:

• Documented beneficial effect from therapy during neurology follow up

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 32 of 91 Drug Prior Authorization Criteria • Preferred glatiramer acetate [Glatopa 20mg/ml] will be covered for new members to KP already taking non-preferred glatiramer acetate [Glatiramer 40 mg/ml, Copaxone 20mg/ml, or Copaxone 40mg/ml].

Continued approval: 1 year

GLP-1 Receptor Non-preferred GLP-1 RAs: Only to be used when the preferred GLP-1 RA (Bydureon™) and Victoza Agonists (GLP- have failed. 1RAs) ** GLP-1 RAs are not substitutes for insulin in patients whose diabetes may benefit from insulin Preferred: treatment Bydureon™ Pen Bydureon® B- ***Note: In patients with clinical atherosclerotic cardiovascular disease (ASCVD) (includes acute Cise™ coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial (Exenatide revascularization, stroke, TIA, carotid stenosis ≥50%, or symptomatic peripheral arterial disease Extended-Release) presumed to be of atherosclerotic origin) consider the use of empagliflozin (Jardiance) if additional medications are needed to achieve glucose control. Non-Preferred: Victoza® The preferred GLP-1 RAs will be covered for current KP new start members who meet ALL of the (Liraglutide) * following criteria:

*Victoza 1.2 mg 1. Documented diagnosis of type 2 diabetes mellitus in patients > 18 years of age preferred over 1.8 2. A1c within 1% of goal in the past 3 months mg a. A1c goal < 7% for patients 18-64 years of age b. A1c goal of at least < 8% is acceptable for patients > 65 years of age, or for Byetta™ patients 18-64 years of age with a history of dementia, blindness, lower (Exenatide) extremity amputation, CKD 4/5, ESRD, cardiomyopathy/CHF, or history of cardiovascular disease (MI, CABG, percutaneous coronary intervention, angina, Trulicity® thoracoabdominal aneurysm, carotid stenosis, renal atherosclerosis, peripheral (Dulaglutide) vascular disease) 3. Failed to obtain adequate glycemic control on combination therapy with: Adlyxin® a. Metformin at least 1000mg per day (adherence > 80% for 3 months) unless (lixisenatide) patient is not a candidate for metformin AND *Note: If GI intolerance on metformin IR, must complete a trial metformin Soliqua® SR 500mg 1 tab po daily for 7 days then titrate to metformin SR 500mg 1 (Insulin tab po bid as tolerated glargine/lix- esenatide) b. Sulfonylurea (adherence > 80% for 3 months) unless the patient is not a candidate for sulfonylurea therapy or the patient is already on multiple daily Xultophy® insulin injections (i.e prandial insulin) AND (Insulin c. Insulin: For non-obese patients (BMI ≤29) an insulin dose of 0.4-0.6 degludec/lira- units/kg/day and for obese patients (BMI ≥30) an insulin dose of 0.8 – 1.2 glutide) units/kg/day) OR

i. The GLP-1 agonist may be initiated prior to insulin trial if patient meets Ozempic® (Semaglutide) ONE of the following criteria: 1. Commercial driver’s licenses OR **NOTE**: *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 33 of 91 Drug Prior Authorization Criteria Non-preferred 2. Significant weight gain (≥ 5% increase in body weight after 6 GLP-1 receptor months of starting a diabetes agent) OR agonists are only 3. Prescriber indicates promotion of weight loss is a major to be used when a consideration and this patients HgbA1c is close to target preferred GLP-1 HbgA1c level is close to target (<8) (For patients with BMI 35 receptor agonist and above). (Bydureon™ or Byetta™) has 4. Patient is not currently on an agent in any of the following classes: GLP-1 RAs, SGLT2 failed. inhibitor, and DPP-4 inhibitors 5. Documented trial, intolerance or contraindication to Bydureon, if request is for non- preferred GLP-1 agonist.

Initial approval period: 5 months. Patient must obtain A1c after 3 months of initiating therapy (this lab should be ordered when initiating therapy).

Continued approval: 1 year, based on: 1. Adherence (> 80%) to diabetic regimen AND 2. Documented HgbA1c lowering of 0.5% from initial A1c to result in a sustained A1c of ≤7.9%% (must be performed within the past 3-6 months).

Members new to KP taking Bydureon™ (preferred GLP-1 RAs or a non-preferred GLP-1 RAs initiated prior to enrollment:

Will be covered for those who meet ALL of the following criteria: 1. Documented diagnosis of type 2 diabetes mellitus AND 2. Metformin dose at least 1000mg per day unless patient is not a candidate for metformin AND *Note: If GI intolerance on metformin IR, must complete a trial metformin SR 500mg 1 tab po daily for 7 days then titrate to metformin SR 500mg 1 tab po bid as tolerated 3. Adherence to sulfonylurea (unless patient is not a candidate or cannot tolerate) AND 4. A1c < 8% within 30 days AND 5. Patient is not currently on an agent in any of the following classes: GLP-1 RAs, SGLT2 inhibitor, and DPP-4 inhibitors AND 6. Documented trial, intolerance or contraindication to Bydureon, if request is for non- preferred GLP-1 Agonist.

Continued Approval: 1 year Based on: 1. Adherence (> 80%) to diabetic regimen AND 2. A1c of ≤8% (must be performed within the past 3-6 months).

Reasons for non-coverage: 1. Type 1 diabetes mellitus 2. Treatment of diabetic ketoacidosis 3. Concurrent use with meglitinides (i.e., repaglinide, nateglinide), or alpha-glucosidase inhibitors (i.e., acarbose, miglitol) *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 34 of 91 Drug Prior Authorization Criteria 4. Pediatric patients (<18 years old) 5. ESRD or severe renal impairment (CrCl <30 mL/min) 6. Patients with severe gastrointestinal disease (including gastroparesis) 7. Diagnosis of pancreatitis, including hemorrhagic and necrotizing, prior to or after initiation of GLP-1 RAs (postmarketing cases, including fatalities, have been reported, therapy should be discontinued immediately). 8. Personal or family history of medullary thyroid cancer (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

Growth Candidates for treatment with Growth hormones should meet ALL the following criteria: hormones: ** Note: For all first time approvals, Omnitrope® is the first-line agent when growth hormone is Preferred: indicated for growth hormone deficiency. Omnitrope® should be tried before approval is granted for other growth hormone agents. Omnitrope® cartridges for use Criteria for use of growth hormones in children (<18 years of age): in pen 1. A diagnosis of Turner’s Syndrome that is confirmed by abnormal karyotype in female children greater than five years of age with appropriate timing and use of hormone replacement therapy; OR Non-preferred: 2. Patients who have a diagnosis of classical growth hormone deficiency and who meet all the Gentropin® criteria below: a. Height is consistently two standards deviation below mean for like age, pubertal Humatrope® maturation and gender over at least one year of serial measurements; and Norditropin® b. Growth velocity that is less than the tenth percentile of normal for like age, pubertal Nutropin AQ® maturation and gender over at least one year of serial measurements; and Saizen® c. Two provocative tests for growth hormones secretion with neither having a Peak > Serostim® 10 ng/ ml; OR Zorbtive® **Bone age determination within six months of the request, reflecting more than two standards deviations below that for like age and gender; with (c.) AND either (a.) or (b.), OR **NOTE**: 3. Children with Prader-Willi Syndrome confirmed by appropriate genetic testing WITHOUT Non-preferred therapeutic contraindications: severe obesity or respiratory impairment; OR growth hormone 4. Pre-pubertal children with chronic renal insufficiency, before renal transplant, providing: is only to be used nutritional status optimized; metabolic abnormalities optimized; and steroid therapy when preferred minimized; OR (Omnitrope®) 5. Patients who are small for gestational age and meet all the criteria below: a. Patient is 2 years of age or older growth hormone b. Child was born small for gestational age, defined as birth weight and/or length at has failed least two standard deviations below the mean for gestational age. c. Child fails to manifest catch-up growth by two years of age, defined as height at least two standard deviations below the mean for age and sex.

**Note: Bone age reflects the potential for the response to GH.

Height standard deviation score for chronologic age increase throughout all treatment years, but for bone age (BA) did not change significantly. Human GH treatment cannot make up a deficit in height prognosis already present at diagnosis, but prevents further loss of stature, which is why early diagnosis is important so that GH therapy can be instituted before significant height for BA deficit has occurred. (J Pediatr 1988;112:875-9).

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 35 of 91 Drug Prior Authorization Criteria Discontinuation of treatment: Treatment with growth hormone will be discontinued if one or more of the following occurs: 1. Height velocity is not at or above the tenth percentile for like age, pubertal maturation and gender after one year of treatment (i.e. the treatment is not effective in achieving a significant increase in stature after one year of treatment). a. Height velocity must be obtained by at least two measurements over a one-year period on stable HGH dosage; 2. Bone age is greater than or equal to 14 years of age for females and 16 years of age for males; OR 3. The patient achieves a height that is within the 3rd percentile for normal adult height for the same sex

Criteria for use of growth hormones in adults (>18 years of age):

Initial Evaluation 1. The patient has one of the following: a. The patient has growth hormone deficiency syndrome, either alone or with multiple hormone deficiencies, as a result of pituitary disease, hypothalamic disease, surgery, radiation or trauma OR b. Patients who were growth hormone-deficient during childhood who have growth hormone deficiency syndrome confirmed as an adult before replacement therapy is started AND 2. The patient has failed at least one growth hormone (GH) stimulation test as an adult a. Failure of GH stimulation test is defined as: i. A peak GH value of <5 mcg/L after stimulation when measure by RIA (polyclonal antibody) OR ii. A peak GH value of <2.5 mg/L after stimulation when measured by IRMA (monoclonal antibody)

Reasons for Non-Coverage: • Growth hormone should not be administered or covered in patients with any of the following: o Acute critical illness (e.g., with complications after cardiac or abdominal surgery, with multiple accidental trauma, or with acute respiratory failure) o Evidence of active malignancy [One possible approach would be to consider growth hormone therapy if the patient has been free of active malignancy for one year after therapy for pituitary tumor or five years after other malignancies.] o Proliferative retinopathy o Uncontrolled hypertension o Benign intracranial hypertension o Pregnancy (relative contraindication due to lack of study evidence and the fact that placental GH is secreted in the second and third trimester.) • Growth hormones will not be covered when being used for any of the following: o Performance enhancement in athletes o Treatment of obesity o Prevention or delay of the aging process o Treatment of partial growth hormone deficiency

Initial Approval Period: 12 months

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 36 of 91 Drug Prior Authorization Criteria

Continued Evaluation 1. The patient has been approved for GH previously through QRM AND 2. The patient is being monitored for adverse effects of GH AND 3. The patient’s IGF-1 level has been evaluated to confirm the appropriateness of the current dose AND 4. The patient has had benefits from GH therapy in any of the following response parameters; body composition, hip-to-waist ratio, cardiovascular health, bone mineral density, serum cholesterol, physical strength, or quality of life.

Continued Approval Period: 12 months Harvoni Candidates for treatment with Harvoni should meet ALL the following criteria: (ledipasvir/sofosb uvir) 1. Is the medication prescribed by a Gastroenterologist or Infectious Disease specialist? If yes, go to #2 If no, go to #8

2. Does patient have a documented Hepatitis C Virus RNA PCR quantitative in the previous 90 days?

If Yes, Go to #3 If No, Go to #8

3. Has the patient been treated previously with Harvoni, Daklinza, Epclusa, Viekera or Zepatier?

If Yes, Contact KP Hepatology Clinic if outside referral (Lisa Woolard, PharmD 770- 677-5869) If No, go to #4

4. Does patient have documented genotype 1 If Yes, Go to #5 If No, Go to #8

5. Does the patient have an eGFR of > 30 ml/min/1.73 m2? If Yes, go to #6 If No, Go to #8

6. Does the patient meet criteria for 8-week Harvoni Treatment? a. Treatment- naïve AND b. Baseline Viral Load < 6 million IU/ml AND c. Non-Cirrhotic AND d. Not co-infected with HIV

If Yes, Go to #7 If NO, go to #8

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 37 of 91 Drug Prior Authorization Criteria 7. Patient qualifies for Harvoni x 8 weeks; Please contact KP Hepatology (Lisa Woolard, PharmD 770-677-5869) OR KP Infectious Disease (Adanna Igboko, PharmD 770-431-4486), if outside referral.

8. Patient does NOT meet criteria for 8- week Harvoni Treatment. Please contact KP Hepatology (Lisa Woolard, PharmD 770-667-5869), if outside referral.

Approval: 8 weeks total duration

GI or ID specialist will call after start of therapy if patient needs to stop or change therapy

Dosage and Administration Recommended dosage: One tablet (90 mg of ledipasvir and 400 mg of sofosbuvir) taken orally once daily with or without food.

Hemlibra Candidates for treatment should meet all the following criteria: (Emicizumab- kxwh) 7. Diagnosis of hemophilia A (congenital factor VIII deficiency) 8. Documented history of clinically significant factor VIII inhibitor 9. Prescribed by a Hematologist/Oncologist 10. Nonresponsive to first-line therapy of immune tolerance induction (ITI), or is not a candidate for ITI (e.g. cannot undergo central line placement), or requires prophylaxis while on ITI therapy. a. ITI is frequent, continuing exposure to factor VIII in order to achieve tolerance by antigen overload. Reasons for non-coverage: • Hemophilia A without inhibitors

Initial Approval: 3 months

Continued Approval: 6 months if ALL the following are met: • Adherence to follow-up assessments and the medication, • No reports of severe adverse events • Documentation of improvement in bleeding rates.

Criteria for Discontinuation: • Non-adherence with follow-up assessments and/or medication • Intolerance to Hemlibra • Discontinuation or temporary discontinuation may be considered if: o Patient successfully completes ITI therapy o Bleed rates do not improve while on Hemlibra o Patient is being evaluated and treated for bleeds o Patient is undergoing a surgery *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 38 of 91 Drug Prior Authorization Criteria Dosage and Administration • 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly Hetlioz® Candidates for treatment with Hetlioz® should meet ALL the following criteria: (tasimelteon) 1. Prescribed by a specialist trained in sleep disorders 2. Patient has documented diagnosis of Non-24-Hour Sleep-Wake Disorder 3. Must have a log of when the patient sleeps and is awake that supports the diagnosis of Non- 24-Hour Sleep-Wake Disorder 4. Patient must be totally blind and have no light perception 5. Patient must have no other concomitant sleep disorder (i.e. sleep apnea, insomnia) 6. The patient has received at least 6 months of continuous therapy (i.e., 6 consecutive months of daily treatment) with melatonin under the guidance of a physician who specializes in the treatment of sleep disorders 7. The patient did not achieve adequate results with melatonin therapy according to the prescribing physician (e.g., entrainment, clinically meaningful or significant increases in nighttime sleep, clinically meaningful or significant decreases in daytime sleep) 8. Documented inadequate response or unable to tolerate Rozerem

Reasons for non-coverage: • Patient has severe hepatic impairment

Initial Approval: 2 months

Continued Approval: • Hetlioz should be discontinued if after 2 months of initiated treatment the patient has not significantly improved from response received during melatonin 6 month trial. • If after 2 months of initiated treatment, the patient has documented positive clinical response to Hetlioz therapy (e.g., entrainment, clinically meaningful or significant increases in nighttime sleep, clinically meaningful or significant decreases in daytime sleep), then 12 months of continued approval.

Dosage and Administration • One 20-mg capsule prior to bedtime, at the same time every night. Human C1 Candidates for treatment with Cinryze® or Haegarda® should meet ALL the following criteria: Esterase Inhibitors 1. A diagnosis of Type I or Type II hereditary angioedema. 2. Prescriber must be an allergist. Cinryze® 3. Contraindications or inability to tolerate 17α-alkylated androgens (ex.danazol, oxandrolone (Human C1 and stanozolol) (especially in females of child-bearing age), including hirsutism, menstrual esterase Inhibitor) irregularities, hepatic dysfunction, undiagnosed vaginal bleeding, porphyria, cardiac or renal Intravenous disease, depression, muscle cramps and thrombosis. Patients with significant lipid abnormalities might also be considered. 4. Lack of response to currently available therapies such as 17α-alkylated androgens as Haegarda® evidenced by lack of symptom control. (Human C1 5. Patients must be at least 9 years of age for Cinryze and at least 12 years of age for Haegarda

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 39 of 91 Drug Prior Authorization Criteria Esterase Inhibitor) 6. Special circumstances may include use in pregnant females with hereditary angioedema subcutaneous (HAE). [Note: Studies in pregnant women have not been conducted and the effects on the fetus or on reproductive capacity are not definitively known. At this time, Cinryze® and Haegarda® should be given to a pregnant woman only if clearly needed.]

Reasons for non-coverage: • Treatment of angioedema acute attacks in adult and adolescent patients with HAE

Initial Approval: 3 months

Continued Approval: 12 Months; Approval will be based on clinical documentation of functional improvement, a decrease in frequency of HAE attack, and an improvement in severity and duration of attacks. Short-term Prophylaxis (to prevent an attack): 1. Minor Procedures: Use of human C1 inhibitor is not required before minor manipulations if human C1 inhibitor is immediately available. As an alternative, danazol can be used in appropriate patients (starting at least 7days before the procedure). 2. Major Procedures or Intubation: Consider the use of human C1 inhibitor for short-term prophylaxis to prevent attacks of angioedema when a patient with HAE has a planned exposure to a situation likely to trigger an attack, such as substantial dental work, invasive medical procedures, and surgical procedures. a. Doses of 500-1,500 units intravenously given one hour before the provoking event have been studied. b. Two doses of human C1 inhibitor should be available. c. Although there is limited data in the United States regarding the use of human C1 inhibitor in pregnancy, a set of international consensus guidelines state that human C1 inhibitor is the safest prophylactic agent to use during pregnancy.

Long-term Prophylaxis (to minimize frequency and severity of recurrent attacks): For patients with HAE who experience ≥ 1 severe event per month or who are disabled more than five days per month OR if the patient has a history of previous airway compromise, consider long-term prophylaxis. Options include: 1. 17α-alkylated androgens (danazol, stanozolol if available, and oxandrolone): Generally treatment of choice for long-term preventative treatment. Contraindications include pregnancy, breastfeeding, significantly impaired renal/ hepatic function, etc (refer to package insert for complete list). See Milan or Budapest Protocols for dosing recommendations. Use in children should be undertaken only with great caution. 2. Antifibrinolytics (epsilon aminocaproic acid [Amicar®]): Less effective than androgens. Often reserved for patients who do not tolerate or in whom anabolic androgens are contraindicated. 3. Human C1 inhibitor replacement: May be necessary in patients in whom androgens are not effective (frequent angioedema attacks), not tolerated or contraindicated. Human C1 inhibitor prophylaxis is the safest prophylactic agent to use during pregnancy *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 40 of 91 Drug Prior Authorization Criteria Hyaluronic Acid Candidates for treatment with Hyaluronic Acid Injection should meet ALL the following criteria: Injection: 1. Patient has clinically documented osteoarthritis of the knees (American College of Preferred: Rheumatology criteria) confirmed by history, exam, x-ray, and synovial fluid analysis, and requested for use in knee Supartz® (P) 2. Failed or intolerant to nonpharmacological therapies (physical therapy, ice, weight loss, etc.)

3. Documented inadequate control of pain or intolerance to an adequate trial (at least 3 months) Non-preferred: of ONE of the following: acetaminophen (4 grams/day), NSAIDs, and other non-narcotic or Synvisc® (2nd Line) narcotic analgesics 4. Documented inadequate trial with intra-articular corticosteroid injection (i.e efficacy Euflexxa® (N) lasting less than 6-8 weeks) Hyalgan® (N) Initial Approval: 1 to 5 weeks depending on the product Synvisc-One® (N)

Criteria for Continuation of Therapy: **Note**: There are no data on repeated courses of therapy for Euflexxa® and Supartz®; there is no evidence of i Supartz® is the ncreased adverse drug events in repeated courses of therapy for Hyalgan®, Synvisc®, and Orthovisc® w preferred hen separated by at least six months. medication. Synvisc® may be **Note: Supartz® is the preferred medication. Synvisc® may be approved if Supartz® is deemed ineffective or the patient has intolerance to Supartz®. approved if

Supartz® is deemed ineffective or the patient has intolerance to Supartz®. Ilaris® Candidates for treatment with Ilaris® should meet ALL the following criteria: (Canakinumab) Criteria for cryopyrin-associated periodic syndromes (CAPS): 1. Documented diagnosis of cryopyrin-associated periodic syndromes (CAPS) 2. Documented laboratory evidence of a genetic mutation in the Cold-Induced Auto-inflammatory Syndrome 1 (CIAS1- sometimes referred to as the NLRP3). 3. Clinical documentation that the patient is experiencing classic symptoms of CAPS in either criteria below: a. Familial Cold Auto-Inflammatory Syndrome (FCAS): recurrent episodes of rash, fever/chills, and joint pain following exposure to mild cold environment. (e.g. cool breeze, air conditioning) Symptoms generally last for up to 24 hours. b. Muckle-Wells Syndrome (MWS): chronic fever and rash sometimes exacerbated by generalized cold exposure. Episodes can last up to 2-3 days. 4. Clinical documentation of significant functional impairment leading to limitations of activities of daily living (ADLs). 5. Documented inadequate response or inability to tolerate either of the following: a. Prednisone b. Anakinra (Kineret®) injection

Criteria for systemic juvenile idiopathic arthritis (SJIA) 1. Documented diagnosis of systemic juvenile idiopathic arthritis (SJIA) *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 41 of 91 Drug Prior Authorization Criteria 2. Prescribed by a rheumatologist 3. Documented inadequate response or inability to tolerate at least ONE of the following a. Methotrexate b. NSAIDs c. Intraarticular glucocorticoid injections 4. Documented inadequate response or inability to tolerate to a tumor necrosis factor–α (TNF- α) inhibitor (i.e., Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab)) 5. Documented inadequate response or inability to tolerate to TWO of the following: a. Actemra (tocilizumab) b. Kineret (anakinra) c. Orencia (abatacept)

Reasons for non-coverage: • Concurrent use of immunosuppressive therapy • Chronic, active, or recurrent infections • Untreated latent tuberculosis • Under 2 years of age (systemic juvenile idiopathic arthritis (SJIA)) or under 4 years of age (cryopyrin-associated periodic syndromes (CAPS))

Initial approval period: 1 month

Continued approval: Up to 1 year based on physician documentation of disease stability and improvement.

Caution: • Concurrent use with live vaccines not recommended • Increased risk of malignancies may occur • Infections, serious (mostly upper respiratory tract) have been reported; discontinue if serious infection develops

Monitoring: • Serum C reactive protein and serum amyloid A levels periodically • Improvement in signs and symptoms of cryopyrin-associated periodic syndromes (ie, fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis) or systemic juvenile idiopathic arthritis (SJIA) • Latent tuberculosis test prior to initiating therapy

Dosing: Cryopyrin-associated periodic syndromes (CAPS) • The recommended dose of Ilaris® is 150 mg for CAPS patients with body weight greater than 40kg. • For CAPS patients with body weight between 15 kg and 40 kg, the recommended dose is 2mg/kg.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 42 of 91 Drug Prior Authorization Criteria • For children 15 to 40 kg with an inadequate response, the dose can be increased to 3mg/kg. • Ilaris is administered every 8 weeks as a single dose via subcutaneous injection.

Systemic juvenile idiopathic arthritis (SJIA) • The recommended dose for patients with body weight ≥ 7.5 kg is 4 mg/kg • Administered every 4 weeks via subcutaneous injection • Maximum: 300 mg/dose Immune globulin Candidates for treatment with SC Immune Globulin should meet the following criteria: (Subcutaneous): 1. Diagnosis of primary immunodeficiency (including but not limited to congenital Hizentra (immune agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, globulin Wiskott-Aldrich syndrome, and severe combined immunodeficiencies) in patients 2 years and subcutaneous) older OR diagnosis of Inflammatory demyelinating polyneuropathy in adults (Hizentra only) AND Hyqvia (Immune 2. Documented systemic adverse reaction during or after an IV infusion OR globulin Infusion 3. Documented limited venous access OR with Recombinant 4. Documented intolerability from relatively large intermittent IV doses OR Human 5. Documented suboptimal clinical conditions resulting from low immune globulin serum trough hyaluronidase) level OR 6. Documented risk for thromboembolic events or hemolysis AND

*Note: Subcutaneous Immune Globulin is NOT administered in Infusion centers

Initial Approval: 3 Months

Continued Approval: 12 months if patient has documented clinical benefit.

Dosage and Administration:

• Hizentra: Administer at regular intervals from daily up to every 2 weeks. • Hyqvia: Administer at 3 to 4 week intervals, after initial treatment Ramp-up.

Impavido® Candidates for treatment with Impavido® should meet the following criteria: (miltefosine) *If Member contracted Leishmaniasis during active military duty, Please contact Veteran’s Affairs for Coverage.

1. Prescribed by Infectious Disease 2. Documented diagnosis of visceral, cutaneous, or mucosal leishmaniasis 3. 12 years of age or older 4. Documented negative pregnancy test (urine or serum) in females of reproductive potential prior to prescribing Impavido. 5. Females of reproductive potential should use effective contraception during Impavido therapy and for 5 months after therapy. 6. Documented inadequate response, intolerance, or contraindication to Amphotericin B intravenous therapy.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 43 of 91 Drug Prior Authorization Criteria

Reasons for Non-Coverage:

1. Known or suspected pregnancy 2. Sjogren-Larsson-Syndrome

Approval period: 28 days

Dosing:

• 30-44 kg: 50 mg twice daily for 28 consecutive days • 45 kg or greater: 50 mg three times daily for 28 consecutive days. Ingrezza® Candidates for treatment should meet the following criteria:

(Valbenazine) 1. Documented diagnosis of tardive dyskinesia 2. Prescribed by a neurologist or psychiatrist 3. Patient is 18 years and older 4. Documented inadequate response, intolerance or contraindication to at least 2 of the agents listed below: a. Clonazepam b. Quetiapine or clozapine c. Amantadine d. Tetrabenazine

Reasons for non-coverage: • Coadministration with or within 14 days of discontinuing monoamine oxidase inhibitors (MAOIs) [i.e. isocarboxazid, phenelzine, selegiline] • Patients taking other VMAT2 Inhibitors [tetrabenazine (Xenazine) or deutetrabenazine (Austedo) • Patients with congenital long QT syndrome or with arrhythmias associated with prolonged QT interval. • Coadministration with a strong CYP3A4 inducer (rifampin, carbamazepine, phenytoin, St. John’s wort)

Initial Approval: 3 months Continued Approval: 12 months if there is documented evidence of improvement in disease symptoms or stabilization of disease state beyond that achieved with prior therapy. Discontinue therapy if no improvement over prior therapy after 3 months. Dosage and Administration • 40 mg once daily; after 1 week, increase to 80 mg once daily. Continuation of 40 mg once daily may be considered for some patients based on response and tolerability.

Interferon beta- Non-preferred Peginterferon beta-1a (Plegridy): Only to be used when Interferon beta-1a (Avonex, 1a: Rebif) has failed. Preferred: Avonex Candidates for treatment with Avonex, Rebif should meet the following criteria: Rebif Non-preferred: 1. Diagnosis of relapsing multiple sclerosis AND Plegridy 2. Prescribed by a neurologist AND 3. Medication is to be used as monotherapy disease-modifying treatment of MS AND 4. At least one of the following a. Presence of significant non-modifiable barriers prohibiting use of preferred disease-

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 44 of 91 Drug Prior Authorization Criteria modifying therapies requiring reconstitution or requiring administration of multiple injections a week eg: clinically confirmed cognitive impairment or pediatric patient OR b. A documented history of severe injection site reactions not responsive to conservative measures (eg: lipoatrophy or skin necrosis) while taking an injectable MS medication (Extavia [preferred interferon], Betaseron, Glatopa, Copaxone) *NOTE: Injection fatigue or fear of needles are not reasons for intolerance or inadequate response.

Note: Extavia is the preferred first-line interferon therapy. Recommend Extavia if appropriate. Candidates for treatment with Plegridy should meet the criteria above and have tried and failed Avonex.

Reasons for non-coverage: Avonex, Plegridy or Rebif should NOT be used in patients with ANY of the following:

• History of treatment-resistant psychosis, depression or suicidal ideation/behavior • Severe hepatic impairment

Initial approval period: 1 year

Continued approval for treatment with Avonex should meet ALL the following criteria: • Documented beneficial effect from therapy during neurology follow up Continued approval: 1 year

Dosage and Administration • The recommended dose of Avonex is 30 mcg injected intramuscularly weekly • The recommended dose of Plegridy is 125 mcg injected subcutaneously every 14 days The recommended dose of Rebif is 22 or 44 mcg injected subcutaneously three times weekly Interleukin (IL) Non-preferred agents: Only to be used when the preferred agent (Stelara®) has failed. The Antagonists: preferred agent, Stelara®, will be covered for candidates who meet ALL of the following criteria:

Preferred: Criteria for use for diagnosis of plaque psoriasis or psoriatic arthritis:

Stelara® 1. Documented moderate to severe plaque psoriasis (OR active psoriatic arthritis for Stelara®) (Ustekinumab) 2. Prescribed by a dermatologist (OR rheumatologist for Stelara®) 3. Documented inadequate response (of at least a 3-month trial), intolerance, or Non-preferred: contraindication to BOTH of the following: a. ONE or more tumor necrosis factor (TNF-α) inhibitors Taltz® i. Humira® (adalimumab) (Ixekizumab) ii. Enbrel® (etanercept) iii. Inflectra® or Remicade® (infliximab) Tremfya® b. Cosentyx® (secukinumab) (guselkumab) 4. Patient has documented negative test for tuberculosis within the past 12 months 5. Documented inadequate response, intolerance, or contraindication to other IL-17 Antagonists (Stelara, Taltz) prior to trialing Siliq

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 45 of 91 Drug Prior Authorization Criteria Siliq™ **Note: Siliq has restricted access through the Siliq Risk Evaluation and Mitigation (Brodalumab) Strategies Program

Criteria for Stelara® use for diagnosis of Crohn’s disease:

1. Documented moderately to severely active Crohn’s disease 2. Prescribed by a gastroenterologist 3. Inadequate response or an inability to tolerate ONE conventional therapy (i.e. sulfasalazine, mesalamine, azathioprine, or 6-mercaptopurine) 4. Inadequate response or an inability to tolerate corticosteroids (i.e. prednisone, methylprednisolone, budesonide) 5. Documented inadequate response (of at least a 3-month trial), intolerance, or contraindication to the following: a. ONE of the TNF-α inhibitors listed below i. Humira® (adalimumab) ii. Inflectra® or Remicade® (infliximab) 6. Patient has documented negative test for tuberculosis within the past 12 months

Reasons for non-coverage:

Agents should NOT be used in patients with any of the following:

• Patients under 18 years old (EXCEPT STELARA) • Presence of active severe infection or history of recurrent severe infections • Should not be used concomitantly with a TNF- α inhibitor

Initial Approval: 6 months

Continued Approval: 12 months if patient has documented a clinically significant benefit from medication.

Jetrea® Candidates for treatment with Jetrea® should meet ALL the following criteria: (Ocriplasmin) 1. Patient is at least 18 years of age 2. Prescribed by a retinal specialist 3. Patient has a documented diagnosis of symptomatic vitreomacular adhesion to the macula within a 6-mm central retinal field surrounded by elevation of the posterior vitreous cortex, as seen on optical coherence tomography (OCT) (these symptoms may include, but are not limited to visual distortion, black spots, or floaters). 4. The vitreo-macular adhesion has been observed over a period of 6 or more weeks for spontaneous resolution 5. Patient has best-corrected visual acuity of 20/25 or less in the affected eye

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 46 of 91 Drug Prior Authorization Criteria Reasons for non-coverage: Jetrea should NOT be used in patients with ANY of the following: • Proliferative diabetic retinopathy • Neovascular age-related macular degeneration, • Retinal vascular occlusion, • Aphakia, • High myopia (more than −8 diopters), • Uncontrolled glaucoma, • Macular hole greater than 400 μm in diameter, • Vitreous opacification, • Lenticular or zonular instability, • History of retinal detachment in either eye • Prior vitrectomy • Prior laser photocoagulation of the macula, • Prior treatment with ocriplasmin; or • Treatment with ocular surgery, intravitreal injection, or retinal laser photocoagulation in the previous 3 months.

Initial approval: One time only for each eye

Dosage and Administration The recommended dose is 0.125 mg (0.1 mL of the diluted solution) administered by intravitreal injection to the affected eye once as a single dose. Juxtapid™ Candidates for treatment with Juxtapid™ should meet ALL the following criteria: (Lomitapide) 1. Documented clinical and laboratory determined diagnosis of homozygous familial hypercholesterolemia (HoFH) 2. 18 years of age or older 3. Prescribed by a certified REMS provider demonstrated with supporting documentation (signed attestation) *NOTE: For more information and to enroll, please go to the following site: http://www.juxtapidremsprogram.com/ 4. Tried and failed or intolerant to at least THREE of the following: • Simvastatin 40 mg daily • Pravastatin 80 mg daily • Atorvastatin 80 mg daily • Crestor 40 mg daily 5. Documented in the medical record that prior to the initiation of therapy, the patient has been and will continue to follow a low-fat diet supplying <20% of energy from fat 6. Documented Baseline laboratory measures of ALT, AST, alkaline phosphatase, and total bilirubin prior to starting Juxtapid™ 7. If patient is a female of child bearing age, must have a baseline negative pregnancy test (within 1 month) AND must be on at least one form of effective contraception

Reason for non-coverage:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 47 of 91 Drug Prior Authorization Criteria • Moderate or severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests

Initial approval: 6 months

Continued approval for treatment with Juxtapid™ should meet ALL the following criteria: 1. Review of compliance to Juxtapid™ 2. Review of compliance to recommend liver enzyme laboratory testing 3. Documented cholesterol control as evidence by significant LDL lowering from pre-treatment levels

Continued approval: 1 year

Limitations of use: • The safety and effectiveness of Juxtapid™ have not been established in patients with hypercholesterolemia who do not have HoFH • The effect of Juxtapid™ on cardiovascular morbidity and mortality has not been determined Monitoring • Before treatment, measure ALT, AST, alkaline phosphatase, and total bilirubin and then ALT and AST regularly as recommended; obtain a negative pregnancy test in females of reproductive potential • During treatment, adjust the dose of Juxtapid if the ALT or AST are ≥ 3 x ULN

Dosing and Administration • Initiate treatment at 5 mg once daily. Initiate a low-fat diet supplying <20% of energy from fat. • Titrate dose based on acceptable safety/tolerability: increase to 10 mg daily after at least 2 weeks; and then, at a minimum of 4-week intervals, to 20 mg, 40 mg, and up to the maximum recommended dose of 60 mg daily

Ordering Information Juxtapid™ is only available from certified pharmacies that are enrolled in the Juxtapid™ REMS program. At this time, Juxtapid™ is not available through our KP Pharmacies or the KP Specialty Pharmacy. Prescriber’s should complete the Juxtapid™ Prescriber Enrollment Form and fax to Juxtapid™ REMS Program at 855-898-2498 or scan form and email to [email protected]. The Juxtapid™ Prescriber Enrollment form is available at: http://www.juxtapidremsprogram.com/_pdf/JUXTAPID_REMS_Program_Prescriber_Enrollment_Form _editable.pdf Kalbitor® Candidates for Kalbitor® should meet ALL of the following criteria: (Ecallantide) 1. A diagnosis of Type I or Type II hereditary angioedema. 2. Prescriber must be an allergist. 3. Contraindications or inability to tolerate 17α-alkylated androgens (danazol, stanozolol, and oxandrolone) (especially in females of child-bearing age), including hirsutism, menstrual irregularities, hepatic dysfunction, undiagnosed vaginal bleeding, porphyria, cardiac or renal disease, depression, muscle cramps and thrombosis. Patients with significant lipid abnormalities might also be considered. 4. Lack of response to currently available therapies such as 17α-alkylated androgens as

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 48 of 91 Drug Prior Authorization Criteria evidenced by lack of symptom control. 5. Lack of response to Berinert®

Reasons for non-coverage: • Routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE • Under 16 years of age

Initial Approval: 3 months Subsequent approval will be based on clinical documentation of functional improvement, a decrease in frequency of HAE attack, and an improvement in severity and duration of attacks.

Monitoring: • Symptomatic improvement • Symptoms of hypersensitivity reaction during or after infusion

Consider long-term prophylaxis for patients with HAE who experience ≥ one severe event per month or who are disabled more than five days per month OR if the patient has a history of previous airway compromise. Options include: 1. 17α-alkylated androgens (danazol, stanozolol if available, and oxandrolone): Generally treatment of choice for long-term preventative treatment. Contraindications include pregnancy, breastfeeding, significantly impaired renal/ hepatic function, etc (refer to package insert for complete list). See Milan or Budapest Protocols for dosing recommendations. Use in children should be undertaken only with great caution. 2. Antifibrinolytics (epsilon aminocaproic acid [Amicar]): Less effective than androgens. Often reserved for patients who do not tolerate or in whom anabolic androgens are contraindicated. 3. Human C1 inhibitor (Cinryze®) replacement: May be necessary in patients in whom androgens are not effective (frequent angioedema attacks), not tolerated or contraindicated. • Human C1 inhibitor prophylaxis is the safest prophylactic agent to use during pregnancy. Kalydeco™ Candidates for Kalydeco™ should meet ALL of the following criteria: (Ivacaftor) 1. Confirmed diagnosis of cystic fibrosis (CF) 2. Prescribed by a pulmonologist 3. Age 2 years or older 4. At least one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R OR Patients with R117H mutation in the CFTR gene who have clinically significant disease. 5. Patient is not currently taking strong CYP3A4 Inducer (e.g., rifampin, St. John’s wort, rifabutin, phenobarbital, carbamazepine, and phenytoin)

Initial Approval: 6 months

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 49 of 91 Drug Prior Authorization Criteria

Continued Approval: 12 months if: • Patient has documented evidence of response to therapy (e.g. improvement or stable ppFEV1, improvement in BMI, decrease in pulmonary exacerbations) AND • ALT/AST levels have been checked within the last 3 months (ALT/AST should be monitored at baseline, every three months for one year, then once yearly thereafter) • In the event of significant elevations of transaminases, e.g., patients with ALT or AST > 5 X upper limit of normal, therapy should be interrupted. Following the resolution of transaminase elevations consider the benefits and risks of resuming treatment.

Dosing and Administration: • Adults and pediatric patients age 6 years and older: one 150 mg tablet taken orally every 12 hours with fat-containing food. • Pediatric patients 2 to less than 6 years of age and less than 14 kg: one 50 mg packet mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food. • Pediatric patients 2 to less than 6 years of age and 14 kg or greater: one 75 mg packet mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food. • Pediatric patients less than 2 years of age: not recommended. • Reduce dose in patients with moderate and severe hepatic impairment. • Reduce dose when co-administered with drugs that are moderate or strong CYP3A inhibitors. Ordering information: Kalydeco™ is available through the KP Specialty Pharmacy. Prescribers must complete the KP Specialty Pharmacy Kalydeco™ Drug Order Form at http://pharmacy.kp.org/kp- cms/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Object=1198&nodeValue=113 and fax it to KP-Specialty Pharmacy (1-650-301-5790). Keveyis® Candidates for treatment with Keveyis® should meet ALL the following criteria:

(dichlorphen- 15. Documented primary hyperkalemic periodic paralysis or primary hypokalemic periodic amide) paralysis, or related variants 16. Prescribed by a neurologist 17. Patient is 18 year of age or older 18. Documented inadequate response or intolerance, or contraindication to acetazolamide 19. Baseline measurement of serum potassium and bicarbonate 20. Must NOT have any of the following: a. Concomitant use with high dose aspirin b. Severe pulmonary disease, limiting compensation to metabolic acidosis caused by Keveyis® c. Hepatic impairment

Initial Approval: 2 months

Continued Approval: 12 months if patient has documented a clinically significant benefit from medication as defined by the Provider as well as documented measurement of serum potassium and bicarbonate while on therapy.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 50 of 91 Drug Prior Authorization Criteria

Dosage and Administration The recommended dose is an initial dose of 50 mg twice daily; may increase or decrease dosage at weekly intervals (or sooner in case of adverse reaction. ; maximum dose is 200 mg daily. Evaluate response and need for continued therapy after 2 months of treatment. Korlym™ Candidates for treatment with Korlym™ should meet ALL the following criteria: (Mifepristone) 1. Documented diagnosis of Cushing’s syndrome 2. Documented diagnosis of type 2 diabetes mellitus or glucose intolerant secondary to Cushing’s syndrome 3. Prescribed by an endocrinologist 4. Patient has failed surgery or is not a candidate for surgery for Cushing’s syndrome 5. Failed to obtain adequate glycemic control on combination therapy with: a. Maximum tolerated doses of metformin monotherapy (unless patient is not a candidate for metformin therapy) and b. Maximum tolerated doses of a sulfonylurea (unless the patient is not a candidate for sulfonylurea therapy) and c. Maximum tolerated titration of insulin OR meets the following criteria: i. Korlym™ may be initiated prior to insulin trial, if the Endocrinologist indicates hypoglycemia is uniquely undesirable, so unable to use insulin (e.g., in patients who have hazardous jobs) 6. Documented inadequate response to ONE of the following cortisol-blocking medications: ketoconazole, metyrapone (Metopirone), or mitotane (Lysodren) 7. If patient is a female of child bearing age (12-50 years of age), must have a baseline negative pregnancy test (within 1 month)

Reasons for non-coverage: • Pregnant women (Pregnancy Category X) • Concomitant use simvastatin or lovastatin and CYP3A substrates with narrow therapeutic range • Concurrent long-term corticosteroid use • Women with history of unexplained vaginal bleeding • Women with endometrial hyperplasia with atypia or endometrial carcinoma

Initial Approval: 6 months

Continued Approval: 12 months if patient has documented clinical benefit from medication and no reported adverse events to Korlym™

Dosage and Administration • The recommended starting dose for Korlym™ is 300 mg once daily

Monitoring: • Patients should be closely monitored for signs and symptoms of adrenal insufficiency

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 51 of 91 Drug Prior Authorization Criteria • Hypokalemia should be corrected prior to treatment and monitored for during treatment

Ordering information: Korlym™ is only dispensed by CuraScript specialty pharmacy. For more information, visit http://pharmacy.kp.org/KpCMS/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32 Object=1226&nodeValue=113 Kuvan™ Candidates for Kuvan™ should meet ALL of the following criteria: (Sapropterin) 1. Diagnosis of Phenylketonuria 2. Absence of the following medications: a. Medications known to inhibit folate metabolism (eg, methotrexate) b. Nitric oxide-mediated vasorelaxation medications (eg sildenafil, vardenafil, tadalafil) c. Levodopa 3. Currently following a phenylalanine restricted diet

Initial Coverage: 2 months

Continued Coverage: 6 months if patient’s phenylalanine levels have decreased 30% from baseline level

Monitoring: • Monitor blood phenylalanine levels at baseline, after 1 week of treatment, periodically for first month, and regularly thereafter Kynamro™ Candidates for treatment with Kynamro™ should meet ALL the following criteria: (Mipomersen sodium) 1. Documented clinical and laboratory determined diagnosis of homozygous familial hypercholesterolemia (HoFH) 2. 18 years of age or older 3. Prescribed by a certified REMS provider demonstrated with supporting documentation (signed attestation) *NOTE: For more information and to enroll, please go to the following site: http://www.kynamrorems.com/ 4. Tried and failed or intolerant to at least THREE of the following: • Simvastatin 40 mg daily • Pravastatin 80 mg daily • Atorvastatin 80 mg daily • Crestor 40 mg daily 5. Documented in the medical record that prior to the initiation of therapy, the patient has been and will continue to follow a low-fat diet supplying <20% of energy from fat 6. Used as adjunct to lipid lowering medications 7. If patient is a female of child bearing age (18-50 years of age), must have a baseline negative pregnancy test (within 1 month) AND must be on at least one form of effective contraception

Reason for Non-coverage:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 52 of 91 Drug Prior Authorization Criteria • Moderate or severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests • Patients receiving LDL apheresis with the use of Kynamro™

Initial approval: 6 months

Continued approval for treatment with Kynamro™ should meet ALL the following criteria: 1. Review of compliance to Kynamro™ 2. Review of compliance to recommend liver enzyme laboratory testing 3. Documented cholesterol control as evidence by significant LDL lowering from pre-treatment levels

Continued approval: 1 year

Limitations of Use • The safety and effectiveness of Kynamro™ have not been established in patients with hypercholesterolemia who do not have HoFH • The effect of Kynamro™ on cardiovascular morbidity and mortality has not been determined • The use of Kynamro™ as an adjunct to LDL apheresis is not recommended

Monitoring • Before treatment, measure ALT, AST, alkaline phosphatase, and total bilirubin and then ALT and AST regularly as recommended • During treatment, withhold the dose of Kynamro™ if the ALT or AST is ≥3 times the upper limit of normal • Discontinue Kynamro™ for clinically significant liver toxicity

Dosing and Administration • The recommended dose is 200 mg once weekly as a subcutaneous injection • The vial or pre-filled syringe should be removed from 2-8°C (36-46°F) refrigerated storage and allowed to reach room temperature for at least 30 minutes prior to administration

Ordering information: Kynamro™ is only available from certified pharmacies that are enrolled in the program. At this time, Kynamro™ is not available through our KP Pharmacies or the KP Specialty Pharmacy. Prescriber’s should complete and the Kynarmo™ Prescription Authorization and fax to Kynamro™ REMS Program at 877- 596-2676. The prescription authorization form is available at: http://www.kynamrorems.com/~/media/Kynamro/Files/Prescription-Authorization-Form.pdf Lemtrada® Candidates for treatment with Lemtrada should meet ALL of the following criteria: (Alemtuzumab) 1. Diagnosis of relapsing multiple sclerosis (MS) 2. Prescribed by or in consultation with a multiple sclerosis specialist certified by the LEMTRADA REMS program (1-855-676-6326) 3. Patient enrolled in the LEMTRADA REMS program and Lemtrada to be administered at a certified healthcare facility with on-site access to equipment and personnel trained to manage infusion reactions 4. Lemtrada to be administered as monotherapy and not in combination with other disease- modifying therapies for MS

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 53 of 91 Drug Prior Authorization Criteria 5. Evidence of continued inflammatory disease (new MRI lesions and/or relapses) on natalizumab (Tysabri) or rituximab (Rituxan) 6. CBC and thyroid function test within normal range, negative serum HIV antibody test, and negative TB test 7. Females of child bearing age (12-50 years of age) have documentation of a baseline negative pregnancy test within the past month AND either a prescription for birth control (IUD or other contraceptive) or documentation of patient declining contraception and being counseled of the potential risk in pregnancy

Reasons for non-coverage: • Secondary progressive MS and no clinical or MRI evidence of relapses • Infection with Human Immunodeficiency Virus • History of thyroid cancer, melanoma and lymphoproliferative disorders • Concomitant use of antineoplastic or immunosuppressant therapies (eg: adalimumab, alefacept, anakinra, azathioprine, cladribine, cyclophosphamide, cyclosporine, daclizumab, efalizumab, etanercept, fludarabine phosphate, infliximab, intravenous immunoglobulin, leflunomide, mercaptopurine, methotrexate, mitoxantrone, mycophenolate mofetil, mycophenolic acid, pemetrexed, rituximab, trastuzumab)

Approval period: 18 months

Dosage and Administration • 12 mg IV infusion over 4 hours on 5 consecutive days then 12 mg IV infusion over 4 hours on 3 consecutive days 12 months later • Premedicate with corticosteroids prior to Lemtrada infusion for the first 3 days of each treatment course • Administer antiviral agents for herpetic prophylaxis starting on the first day of Lemtrada dosing and continue for a minimum of 2 months after completion of Lemtrada dosing or until CD4+ lymphocyte count is more than 200 cells/µL • Must be diluted prior to administration

Monitoring • Infusion reactions (may be delayed and may be life-threatening) • Recommended at baseline and monthly until 48 months after last treatment course: o CBC w/ differential o Serum creatinine o Urinalysis with urine cell counts • Thyroid function tests at baseline and every 3 months until 48 months after last treatment course • Skin exam at baseline and yearly to monitor for melanoma • For females, human papillomavirus screening yearly • Autoimmune conditions including thyroid disorders and immune thrombocytopenia • Signs or symptoms of infection

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 54 of 91 Drug Prior Authorization Criteria • Signs or symptoms of PML • ECG prior to each treatment course

Ordering information: Prescriber, patient, pharmacy and infusion center must be enrolled in the LEMTRADA REMS program. For information on how to enroll in the program, please visit https://www.lemtradarems.com/ or call 1-855-676-6326. Lemtrada is distributed by the manufacturer to certified pharmacies and infusion centers only. Mavyret™ Candidates for Mavyret should meet ALL of the following criteria: (Glecaprevir/pib- rentasvir) 1. Is the medication prescribed by a Gastroenterologist or Infectious Disease Specialist? If yes, go to #2 If no, patient does NOT meet criteria for Mavyret; go to #7

2. Does the patient have a documented Hepatitis C Virus RNA PCR quantitative in the previous 6 months? If Yes, go to #3 If no, patient does NOT meet criteria for Mavyret, go to #7

3. Does the patient have an eGFR <30 ml/min/1.73 m2 or is on hemodialysis? If yes, go to #4 If no, patient does NOT meet criteria for Mavyret, go to #7

4. Does the patient have decompensated cirrhosis (moderate to severe hepatic impairment, child-Turcotte-Pugh (CTP) Class B or C? If yes, patient does NOT meet criteria for Mavyret, go to #7 If no, got to #5

5. Has patient been previously been treated with an NS5A inhibitor If Yes, go to # 6 If No, patient qualifies for Mavyret therapy, go to #7

6. Does patient have Genotype 1? If yes, Patient qualifies for Mavyret therapy, go to #7 If No, Patient does NOT meet criteria for Mavyret, go to #7

7. Has patient been reviewed by the KP Hepatology clinic or KP Infectious disease service? If yes, continue with Mavyret approval If no, please contact Lisa Woolard, PharmD at 770-677-5869

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 55 of 91 Drug Prior Authorization Criteria Approval:

GI or ID specialist will call after start of therapy if patient needs to stop or change therapy.

Dosage and Administration:

• Three tablets (each tablet contains glecaprevir 100 mg glecaprevir and pibrentasvir 40 mg) taken once daily with food.

Natpara® Candidates for treatment with Natpara® should meet ALL the following criteria: (parathyroid 1. Prescribed by an Endocrinologist hormone) 2. Documented diagnosis of chronic hypoparathyroidism 3. Documented inadequate response or an inability to tolerate maximum titrated doses of conventional therapy (i.e. oral calcium requirement ≥ 2000 mg per day AND calcitriol requirement ≥ 0.25 µg per day) 4. Documented laboratory evidence of sufficient 25-hydroxyvitamin D stores and serum calcium > 7.5 mg/dL 5. No documentation of calcium-sensing receptor mutations

Reasons for non-coverage: Natpara® should NOT be used in patients with any of the following: • Diagnosis of acute post-surgical hypoparathyroidism • Diagnosis of hypoparathyroidism caused by calcium-sensing receptor mutations • History or current diagnosis of osteosarcoma • Paget’s disease of bone or unexplained elevations of alkaline phosphatase • Pediatric and young adult patients with open epiphyses • Hereditary disorders predisposing to osteosarcoma • History of external beam or implant radiation therapy involving the skeleton

Initial approval period: 6 months

Continued approval for treatment with Natpara® should meet ALL the following criteria: 1. Review of compliance to Natpara® 2. Documented beneficial effect from therapy such as reduction in signs or symptoms of disease

Continued approval: 1 year

Dosage and Administration • The initial dose of Natpara® for hypoparathyroidism is 50 mcg once daily as a subcutaneous injection in the thigh (alternate thigh every day). • The dose of Natpara® may be increased in increments of 25 mcg every 4 weeks up to a maximum daily dose of 100 mcg if serum calcium cannot be maintained above 8 mg/dL without an active form of vitamin D and/or oral calcium supplementation. • The dose of Natpara® may be decreased to as low as 25 mcg per day if total serum calcium is repeatedly above 9 mg/dL after the active form of vitamin D has been discontinued and

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 56 of 91 Drug Prior Authorization Criteria calcium supplement has been decreased to a dose sufficient to meet daily requirements.

Monitoring • Serum calcium concentration should be measured within 3 to 7 days of Natpara® initiation and weekly during titration. Doses of calcium and vitamin D should be adjusted based on serum calcium value and clinical assessment. • After dose has been stabilized, monitor serum calcium, albumin and phosphate every 3 to 6 months, and serum creatinine and 24-hr urinary calcium excretion every 6 to 12 months • Monitor for signs and symptoms of hypocalcemia (tingling in fingers and toes, perioral numbness, muscle cramps, laryngospasm, seizures) or hypercalcemia (nausea, vomiting, constipation, low energy, muscle weakness).

*Prescribers and pharmacies will have to participate in the Natpara® REMS program for Natpara® to be made available to the patient. As of February 2015, NPS Pharmaceuticals has not allowed purchasing of Natpara by KP Pharmacy. Prescribers should contact NPS Advantage at 1-855- NATPARA (1-855-628-7872). Nucala® Candidates for Nucala® should meet ALL of the following criteria: (Mepolizumab) 1. Prescribed by a pulmonologist or allergy specialist 2. 12 years of age or older

3. Has a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA or Churg-Strauss Syndrome) OR 4. Has a diagnosis of severe asthma with an eosinophilic phenotype: a. Documented blood eosinophil count of: i. ≥ 150 cells/mm3 at therapy initiation OR ii. ≥ 300 cells/mm3 in the previous 12 months 5. Uncontrolled asthma* despite an aggressive drug therapy regimen including: a. High-dose inhaled corticosteroid (ICS), plus a long-acting beta-agonist (LABA)—e.g. fluticasone 500 mcg/salmeterol 50 mcg (Advair Diskus) 1 puff twice daily WITH b. Daily use of oral corticosteroids (OCS)—e.g. prednisone 5 – 20 mg daily 6. NOTE: Patients who are not on daily OCS but who otherwise meet the above criteria and who have had frequent and/or severe exacerbations in the past 12 months requiring systemic corticosteroids for > 3 days can be considered for mepolizumab (Nucala). 7. NOT for the treatment of other causes of eosinophilia such as hypereosinophilic syndromes, neoplastic disease, or parasitic disease. 8. NOT used for the relief of acute bronchospasm or status asthmaticus 9. NOT currently receiving another monoclonal antibody for the treatment of asthma—e.g. omalizumab (Xolair), reslizumab (Cinqair), benralizumab (Fasenra).

*Indicators of uncontrolled asthma include: two or more exacerbations in the past 12 months requiring systemic corticosteroids for > 3 days, serious exacerbation: at least one hospitalization, ICU stay or mechanical ventilation in the past 12 months, or Asthma Control Test (ACT) is consistently < 20.

Initial Approval: 3 months

Continued Approval: 12 months if the patient has experienced any of the following:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 57 of 91 Drug Prior Authorization Criteria • Member has experienced a reduction in asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath • Member has experienced a decrease in administration of rescue medication, albuterol (e.g. Ventolin, albuterol nebulizing solution) • Member has experienced a decrease in exacerbation frequency (no increase in ICS dose or OCS dose) • Member has experienced an increase in predicted FEV1 from the pretreatment baseline • Member has an objective improvement in quality of life: Asthma Control Test (ACT) • NOTE: Do not approve if member has documented hypersensitivity reactions related to Nucala administration (e.g. anaphylaxis, angioedema, shortness of breath, hypotension, itching, rash)

Dosage and administration: • The recommended dose is 100 mg administered once every 4 weeks by subcutaneous injection into the upper arm, thigh, or abdomen. • Should be reconstituted and administered by a healthcare professional Monitoring: • Monitor the patient for hypersensitivity reactions approximately 60 minutes after the administration of each dose. • FEV1, peak flow, and/or other pulmonary function tests • Frequency of administration of rescue medication (short-acting beta2-agonist, albuterol) • Asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath • Frequency of exacerbation Ocrevus™ Candidates for treatment with Ocrevus™ should meet ALL the following criteria:

(Ocrelizumab) Relapsing multiple sclerosis indication 1. Diagnosis of relapsing multiple sclerosis 2. Prescribed by a Neurologist 3. Must be 18 years of age or older 4. Loss of therapeutic response (recent clinical relapse or increased MRI activity) or severe and persistent infusion reactions after initial adequate clinical response to intravenous rituximab infusion that may be due to suspected development of drug binding or neutralizing antibodies a. Note: The clinical significance of drug binding and neutralizing antibodies is debatable and has not been shown to impact the efficacy or severity of adverse events. In patients with no other reason for loss of therapeutic effect, a switch from rituximab to ocrelizumab may be considered. 5. Patient has been screened for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) and is seronegative or liver specialist consult has been obtained for chronically infected patients (carriers of HBsAg) or patients with unclear status (HBsAg negative but HBcAb positive). 6. Not used in combination with another MS disease modifying agent 7. Absence of an active infection 8. Treatment to be initiated no sooner than 6 weeks after vaccine administration

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 58 of 91 Drug Prior Authorization Criteria OR

Primary progressive multiple sclerosis indication

1. Diagnosis of primary progressive multiple sclerosis 2. Prescribed by a Neurologist 3. Must be 18 years of age or older 4. Adequate clinical response to intravenous (IV) rituximab infusion a. NOTE: If loss of clinical response to IV rituximab, Ocrelizumab should NOT be used for primary progressive multiple sclerosis 5. Presence of severe and persistent infusion reactions on IV rituximab infusion 6. Patient has been screened for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) and is seronegative or liver specialist consult has been obtained for chronically infected patients (carriers of HBsAg) or patients with unclear status (HBsAg negative but HBcAb positive). 7. Not used in combination with another MS disease modifying agent 8. Absence of an active infection 9. Treatment to be initiated no sooner than 6 weeks after vaccine administration

Reasons for non-Coverage: 1. Active HBV virus infection 2. History of life-threatening infusion reaction to rituximab or Ocrevus. 3. Concomitant use of antineoplastic or immunosuppressant therapies (eg: adalimumab, alefacept, anakinra, azathioprine, cladribine, cyclophosphamide, cyclosporine, daclizumab, efalizumab, etanercept, fludarabine phosphate, infliximab, intravenous immunoglobulin, leflunomide, mercaptopurine, methotrexate, mitoxantrone, mycophenolate mofetil, mycophenolic acid, pemetrexed and trastuzumab.

*NOTE: Kaiser Permanente Inter-Regional Practice Recommendations for Multiple Sclerosis recommend rituximab as the preferred, highly effective agent in patients with positive JCV antibody status.

Initial Approval: 6 months Continued Approval: 12 months if patient has documented clinical benefit from medication and no reported severe adverse events to Ocrevus.

Dosage and Administration 1. Initial Dose: 300 mg Intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion. 2. Subsequent doses: single 600 mg intravenous infusion every 6 months. 3. Administer under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions. *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 59 of 91 Drug Prior Authorization Criteria 4. Observe patients for infusion reactions during the infusion and for at least one hour after completion of the infusion. 5. Administer pre-medication (e.g.methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions.

Olysio Olysio is a non-preferred treatment agent at Kaiser Permanente. Please refer all requests to internal (simeprevir) KP Hepatology or Infectious Disease Orkambi® Candidates for treatment with Orkambi® should meet ALL the following criteria: (lumacaftor and ivacaftor) 1. Patient is at least 6 years of age 2. Prescribed by a Pulmonologist 3. Patient has a documented diagnosis of cystic fibrosis 4. Documented homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene 5. Baseline ALT, AST, and bilirubin are provided 6. Baseline ophthalmic examination results are provided in pediatric patients 7. Patient is NOT taking contraindicated medications such as: a. Anti-infectives: rifampin or rifabutin b. Seizure Medications: Phenobarbital, carbamazepine or phenytoin c. Sedatives/Anxiolytics: triazolam or midazolam d. Immunosuppressants: cyclosporine, everolimus, sirolimus, or tacrolimus e. Herbal supplement: St. John’s Wort

Initial approval: 6 months

Continued approval: 6 months if the following criteria are met:

1. Adherence as evidenced by refill history and quarterly clinic visits 2. The prescribing physician determines that the patient is tolerating lumacaftor/ivacaftor therapy and has achieved a clinically meaningful indicator of response in at least one of the following parameters: a) Improvement of percent predicted FEV1 from baseline b) Pulmonary exacerbations c) Body mass index 3. ALT, AST, bilirubin and ophthalmic changes (if appropriate) are adequately monitored Dosage and Administration

• Adults and pediatric patients age 12 years and older: two tablets (each containing lumacaftor 200 mg/ivacaftor 125 mg) taken orally every 12 hours with fat-containing food. • Pediatric patients age 6 through 11 years: two tablets (each containing lumacaftor 100 mg/ivacaftor 125 mg) taken orally every 12 hours with fat-containing food. • Reduce dose in patients with moderate (Two tablets in the morning and one tablet in the evening) or severe hepatic impairment (One tablet in the morning and one tablet in the

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 60 of 91 Drug Prior Authorization Criteria evening). • When initiating Orkambi in patients taking strong CYP3A inhibitors, reduce Orkambi dose for the first week of treatment (1 tablet daily for the first week of treatment. Following this period, continue with the recommended daily dose). a. Strong CYP3A inhibitors include ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin • Concomitant use with a strong CYP3A inducers is NOT recommended a. Strong CYP3A inducers include rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, and St. John’s Wort • Co-administration of Orkambi is not recommended with sensitive CYP3A substrates with a narrow therapeutic index: a. Benzodiazepines: midazolam, triazolam (consider an alternative to these benzodiazepines b. Immunosuppressants: cyclosporine, everolimus, sirolimus and tacrolimus (Avoid the use of Orkambi)

Ordering information:

Orkambi is available through the KP Specialty Pharmacy. If approved for coverage, prescribers must complete the KP-SP Orkambi Order Form and fax it to the KP-Specialty Pharmacy (1-650-301-5790). Parathyroid Candidates for treatment with parathyroid hormone analogs should meet ALL the following criteria: Hormone • Prescribed by endocrinologist or rheumatologist Analogs: • Documented diagnosis of osteoporosis with a very low DEXA T-score < -3.5 or or prior fragility vertebral or nonvertebral osteoporosis-related fracture Forteo® • Documented inadequate response (new osteoporosis-related fracture while on (Teriparatide) bisphosphonate) or intolerance to an oral bisphosphonate (i.e. alendronate, ibandronate, [Preferred] risedronate) • Documented inadequate response, intolerance to an IV bisphosphonate (i.e. zolendronic Tymlos™ acid) or documented clinical reason for not trialing an IV bisphosphonate (Abaloparatide) • Documented inadequate response, intolerance to Prolia (denosumab) unless glucocorticoid- induced osteoporosis • Patient should NOT be on any other therapy for osteoporosis (Prolia, Bisphosphonates, etc.)

Reasons for non-coverage: • Increased baseline risk for osteosarcoma (e.g., Paget’s disease of the bone, pediatric patients or • Young adults with open epiphyses, or history of radiation therapy involving the skeleton) • Bone metastases or a history of skeletal malignancies • Metabolic bone diseases other than osteoporosis • Pre-existing hypercalcemia or primary hyperparathyroidism • Pregnant or nursing women • Patients in whom secondary causes of osteoporosis have not been excluded Previous use with a cumulative duration of >2 years of a PTH analog

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 61 of 91 Drug Prior Authorization Criteria

Initial Approval: 24 months

Dosage and Administration:

Forteo: 20mcg subcutaneously once daily. Tymlos: 80 mcg subcutaneously once daily.

*The cumulative use of parathyroid hormone analogs for more than 2 years during a patient’s lifetime is NOT recommended.

PCSK-9 Inhibitors Candidates for treatment should meet the following criteria: 1. Prescribed by cardiologist or Endocrinologist AND Repatha® 2. Documented diagnosis of atherosclerotic Cardiovascular vascular disease (ASCVD)* or (Evolocumab) familial hypercholesterolemia OR Baseline untreated LDL >/= 190 mg/dl within the past 3 [Preferred] months AND *Clinical ASCVD includes: Acute coronary syndrome: Myocardial infarction, Stable or unstable Praluent® angina, Coronary or other arterial revascularization procedure (such as PTCA, CABG), (Alirocumab) Transient ischemic attack (TIA), Peripheral arterial disease presumed to be of atherosclerotic origin, Findings from CT angiogram or catheterization consistent with clinical ASCVD 3. NOT given in combination with another PCSK9 inhibitor, Kynamro (mipomersen), or Juxtapid (lomitapide), LDL apheresis 4. For Praluent, the patient must have a documented contraindication to, an allergy to, a history of adverse events to, or tried and failed an appropriate dose of evolocumab (Repatha) 5. Patient receiving maximally tolerated statin therapy (PCSK9 inhibitors are only indicated as adjunct to diet and maximally tolerated statin therapy, therefore efforts should be made to continue maximally tolerated statin therapy with these medications).

In addition, for ASCVD the following criteria should also be met: 6. Patient has had an adequate trial of at least 3 months each of a high-intensity statin (atorvastatin 40 mg or 80 mg AND rosuvastatin 20 mg or 40 mg) PLUS ezetimibe 5 mg, AND LDL remains > 130 despite optimal adherence (defined as proportion of days covered > 80% over the last 6 months). OR *Note: Per 2017 ACC Expert Consensus Decision Pathway: Considerations that may favor the initial choice of ezetimibe include: when patients require <25% additional LDL lowering, recent ACS< 3 months, cost, heart failure, hypertension, age > 75 years of age, diabetes, stroke, CABG, PAD, eGFR < 60 ml/min/1.73 m , smoking. If patients with clinical ASCVD require > 25% additional lowering of LDL-C, the addition of a PCSK9 inhibitor may be considered when criteria met. 7. Documented trial and intolerance of at least 3 different statins (two of which must be atorvastatin and rosuvastatin), including an attempted alternative dosing regimen (e.g. every-other day, once or twice weekly) OR documented history of CPK> 10 x ULN or rhabdomyolysis attributed to a statin and not explained by a drug interaction, fall, or *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 62 of 91 Drug Prior Authorization Criteria prolonged immobility OR an absolute contraindication to statin therapy (active, decompensated liver disease; nursing female, pregnancy, or plans to become pregnant; hypersensitivity reaction) a. Other causes of muscle symptoms must be ruled out (e.g. hypothyroidism, Vitamin D deficiency, recent exercise), drug-drug interactions that can increase systemic statin exposure should be considered

OR 8. Documented intolerance OR contraindication to ezetimibe

In addition, for LDL > 190 or familial hypercholesterolemia the following criteria should also be met: 9. Patient has had an adequate trial of at least 3 months each of a high-intensity statin (atorvastatin 40 mg or 80 mg AND rosuvastatin 20 mg or 40 mg) PLUS ezetimibe 10 mg AND LDL has remained > 160 despite optimal adherence (defined as proportion of days covered > 80% over the past 6 months). OR 10. Documented trial and intolerance of at least 3 different statins (two of which must be atorvastatin and rosuvastatin), including an attempted alternative dosing regimen (e.g. every-other day, once or twice weekly) OR documented history of CPK> 10 x ULN or rhabdomyolysis attributed to a statin and not explained by a drug interaction, fall, or prolonged immobility OR an absolute contraindication to statin therapy (active, decompensated liver disease; nursing female, pregnancy, or plans to become pregnant; hypersensitivity reaction) OR 11. Other causes of muscle symptoms must be ruled out (e.g. hypothyroidism, Vitamin D deficiency, recent exercise), drug-drug interactions that can increase systemic statin exposure should be considered 12. Documented intolerance OR contraindication to ezetimibe.

Initial approval: 3 months. Patient must obtain LDL after 3 months of therapy. (This lab should be ordered when initiating therapy).

Continued approval: 12 months if the following criteria are met based on 3 month LDL: 13. Documented adherence (80%) to maximum tolerated doses of statin and ezetimibe (unless patient is not a candidate as outlined above) AND 14. Documented LDL lowering by at least 35% from baseline AND 15. Documented 80% adherence to PCS-K-9 inhibitor

Dosage and Administration: Praluent:

Subcutaneous: 75 mg once every 2 weeks

Repatha: 16. HeFH or ASCVD:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 63 of 91 Drug Prior Authorization Criteria 17. Subcutaneous: 140 mg q 2 weeks or 420 mg q month 18. HoFH: 19. Subcutaneous: 420 mg q month Procysbi™ Candidates for treatment with Procysbi™ should meet ALL the following criteria: (delayed-release Cysteamine) 1. Document diagnosis of nephropathic cystinosis 2. 6 years of age or older 3. Documented inadequate response or unable to tolerate Cystagon®(immediate-release cysteamine)

Reasons for non-coverage: • Hypersensitivity to penicillamine

Initial Approval: 6 months. Maximum dosage approved should be restricted to 1.95 grams/ m2/day.

Continued Approval: 12 months based on review of compliance to therapy and documentation of evidence of response to therapy

Dosage and Administration • Total daily dose is 1.3 gram/m2/day in two divided doses, every 12 hours. • Take Procysbi™ at least 2 hours after and at least 30 minutes before eating

Switching from Cystagon® to Procysbi™ • Total daily dose of Procysbi™ equal to their previous total daily dose of Cystagon®

Initial Dosage in cysteamine-naïve patients • Starting Dose: 1⁄6 to 1⁄4 of the maintenance dose of Procysbi™ • Maintenance Dose: 1.3 gram/m2/day, in two divided doses every 12 hours

Monitoring: • WBC cystine levels (or plasma cysteamine concentration if adequate WBC cystine testing is not available) should be measured as follows: o Monthly for 3 months, then quarterly for 1 year, then twice yearly at a minimum for patients never treated with Cystagon® before. o Two weeks, then quarterly for 6 months, then twice yearly at a minimum for patients switching from Cystagon® to Procysbi™. • WBC cystine and/or plasma cysteamine measurements must be obtained 12.5 hours after the evening dose the day before, and therefore 30 minutes after the following morning dose is given. Prolia® Candidates for treatment with Prolia® should meet ALL the following criteria:

(Denosumab) 1. Prior osteoporotic fracture OR 2. High risk for fracture: WHO Fracture Risk Assessment (FRAX) 10-year risk of hip fracture of ≥3% OR a 10-year risk of a major osteoporotic fracture of ≥20% Web Link to WHO Fracture Risk Assessment Tool (FRAX): http://www.shef.ac.uk/FRAX/tool.jsp 3. Prescribed by Specialist provider (e.g: endocrinologist, rheumatologist, or oncologist)

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 64 of 91 Drug Prior Authorization Criteria 4. Documented inadequate response or intolerance to an oral bisphosphonate (i.e. alendronate, ibandronate, risedronate) 5. Documented inadequate response, intolerance to an IV bisphosphonate (i.e. zoledronic acid®) or documented clinical reason for not trialing an IV bisphosphonate. 6. Calcium levels have been checked and any pre-existing hypocalcemia has been corrected.

Reasons for non-coverage: • Pediatric patients (<18 years old) • Pregnant/nursing women • Hypocalcemia • Non-FDA approved indications

Initial Approval: 6 months (1 dose)

Continued Approval: 12 months (2 doses) if patient has documented clinical benefit from medication

Dosage and Administration • Prolia® should be administered by a healthcare professional • 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily. Provenge® Candidates for Provenge® should meet ALL of the following criteria: (Sipuleucel-T) Prescriber should be enrolled in the Dendreon ON Call Program: (877) 556-3737. Representatives can be reached at (877) 336-3736 to answer general questions, Monday-Friday from 8:00a-8:00pm (ET) and 24 hours per day in the event of a product related health emergency

1. Histological documentation of adenocarcinoma of the prostate without evidence of neuroendocrine or small cell features 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 3. Patient must be asymptomatic or minimally symptomatic, without cancer-related bone pain or use of opiod analgesics for cancer pain 4. Must have Progressive androgen independent prostate cancer. a. Current (i.e., within past 6 months) and continuing evidence of disease progression while on medical castration or after surgical castration demonstrated by: i. PSA progressiona OR ii. progression of measurable diseaseb OR iii. progression of non-measurable diseasec 5. Must have metastatic disease as evidenced by: a. soft tissue metastases on CT of abdomen/pelvis within 6 months OR bony metastases on bone scan within 6 months AND b. no known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 65 of 91 Drug Prior Authorization Criteria 6. Life expectancy of at least 6 months 7. Testosterone < 50 ng/dL achieved via medical or surgical castration a. Medical Castration (Lupron or Zoladex) has occurred and has been continued for at least 3 months OR b. Surgical (orchiectomy) castration must have occurred at least 3 months prior 8. No known pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression. 9. No requirement for systemic immunosuppressive therapy (e.g. corticosteroids) for any reason 10. None of the following may occur within 28 days prior to Provenge®: a. Surgery b. External beam radiation therapy c. Treatment with chemotherapy d. Treatment with other investigational products e. Treatment with other systemic therapy for prostate cancer (except for medication castration with Lupron® or Zoladex®) f. Treatment with 5-α-reductase inhibitors (e.g., finasteride [Proscar®], dutasteride [Avodart®]) g. Treatment with high dose calcitriol [1,25(OH)2VitD] (i.e., > 0.5 µg/day) h. Treatment with ketoconazole i. Treatment with PC-SPES (or PC-SPEC) or Saw Palmetto j. Treatment with megestrol acetate (Megace®), diethylstilbesterol (DES), or cyproterone acetate k. Treatment with non-steroidal antiandrogens (e.g., flutamide, nilutamide or bicalutamide) l. No change (initiation or discontinuation) in bisphosphonate therapy m. No systemic corticosteroids i. Use of inhaled, intranasal, intra-articular, and topical steroids is acceptable, as is a short course (i.e., < 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans n. No use of narcotics for cancer related pain o. Average weekly pain score of > 4 (measured by the Visual Analogue Scale (VAS))14 days prior to treatment initiation 11. The following lab values must be demonstrated prior to therapy initiation: a. White blood cell (WBC) > 2,500 cells/µL b. Neutrophils > 1,000 cells/µL c. Platelets > 100,000 cells/µL d. Hemoglobin (HgB) > 9.0 g/dL e. Creatinine < 2.0 mg/dL f. Total Bilirubin < 2 x upper limit of normal (ULN) g. Aspartate transferase (AST) < 2.5 x ULN h. Alanine transferase (ALT) < 2.5 x ULN i. Serum PSA > 5.0 ng/mL

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 66 of 91 Drug Prior Authorization Criteria Notes: a. PSA Progression: Two consecutive PSA values, at least 14 days apart, each > 5.0 ng/mL and > 50% above the minimum PSA observed during castration therapy or above the pre- treatment value if there was no response. b. Measurable disease: > 50% increase in the sum of the cross products of all measurable lesions or the development of any new lesions. The change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response. c. Non-measurable disease: o Soft tissue disease: The appearance of 1 or more new lesions, and/or unequivocal worsening of non measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. o Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre- existing lesions on bone scan does not constitute progression.

Approval Duration: Up to 3 doses (one course of treatment)

Ordering information: Provenge® is provided only through specified KP treatment sites with training and coordination handled by Dendreon. For more information and to fill out the Kaiser Provenge® Enrollment Form, visit http://kpnet.kp.org/kphealthconnect/deploy/prod/ac/provenge.htm. Radicava® Must meet ALL the following criteria: (Edavarone) 1. Prescribed by a Neurologist 2. ALS Functional Rating Scale-Revised (ALSFRS-R) score* of 2 points or better on each of the 12 items within the past two months 3. Definite or Probable ALS based on El Escorial revised criteria, or Bulbar ALS with proper exclusion of ALS mimickers 4. Duration of 2 years or less from onset of first symptom 5. Forced vital capacity (%FVC) > 80% within past tow months 6. Prior or current use of riluzole 7. Patient willing/able to have a tunneled catheter long-term

Reasons for non-coverage: • Score of < 3 on ALSFRS-R for dyspnea, orthopnea, or respiratory insufficiency

Initial approval: 3 months

Continued approval: 3 months based on adherence to follow-up assessments and documented ALSFRS-R, and % FVC in the medical Record

• Treatment may be discontinued for any of the following:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 67 of 91 Drug Prior Authorization Criteria o Non-adherence to follow-up assessments o Patient is requiring a tracheotomy or non-invasive ventilation all day o %FVC < 50% and blood gas PaCO2 > 45 mm Hg o Significant clinical decline based on ALSFRS-R and/or %FVC o Patient requiring hospice care *ALSFRS-R: A standardized scale from 0 (worst) to 48 (best). The ALSFRS-R scale consists of 12 questions that evaluate the fine motor, gross motor, bulbar, and respiratory function of patients with ALS (speech, salivation, swallowing, handwriting, cutting food, dressing/hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency). Each item is scored from 0-4, with hiher cores representing greater functional ability.

Ravicti™ (glycerol Candidates for treatment with Ravicti™ should meet ALL the following criteria: phenylbutyrate) 1. Documented diagnosis of urea cycle disorder 2. Must be 2 years of age or older 3. Inadequate response to ONE of the following: dietary protein restriction or amino acid supplementation 4. Must be used with dietary protein restriction 5. Documented inadequate response or unable to tolerate Buphenyl® (sodium phenylbutyrate)

Reasons for non-coverage: • Known hypersensitivity to phenylbutyrate • Being used for treatment of acute hyperammonemia in patients with urea cycle disorders

Initial Approval: 6 months

Continued Approval: 12 months if there is documented evidence of response to therapy and patient is actively on dietary protein restriction

Dosage and Administration • Recommended initial dosing range is 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) • Total daily dosage is given in 3 equally divided dosages, rounded up to nearest 0.5 mL • Instruct patients to take with food and to administer directly into mouth via oral syringe or dosing cup • Must be used with dietary protein restriction

Monitoring: • Signs and symptoms of neurotoxicity (eg, confusion, headache, nausea, sleepiness, somnolence, or vomiting) without increased ammonia levels or other illnesses • Plasma ammonia

Ordering information: Ravicti™ is available through the KP Specialty Pharmacy. Prescribers must complete the Ravicti Drug Order Form and fax it to KP-Specialty Pharmacy (1-650-301-5790).

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 68 of 91 Drug Prior Authorization Criteria Ruconest Candidates for treatment with Ruconest® should meet ALL the following criteria: (C1 inhibitor (recombinant)) 1. A diagnosis of Type I or Type II hereditary angioedema (HAE). 2. Prescribed by an allergist. 3. Treatment of acute attacks of HAE in adult or adolescent patients 4. Documented trial and lack of response to 17α-alkylated androgens or contraindications/inability to tolerate 17α-alkylated androgens (especially in females of child- bearing age), including hirsutism, menstrual irregularities, hepatic dysfunction, undiagnosed vaginal bleeding, porphyria, cardiac or renal disease, depression, muscle cramps and thrombosis. Patients with significant lipid abnormalities might also be considered. 5. Documented trial or intolerance to ONE human C1-Inhibitor (Cinryze or Berinert)

Reasons for non-coverage: • Routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE • 18 years of age or younger • Being used in the treatment of HAE patients with laryngeal attacks

Initial Approval: 3 months Subsequent approval will be based on clinical documentation of functional improvement, a decrease in frequency of HAE attack, and an improvement in severity and duration of attacks.

Dosing and Administration: • The recommended dose of Ruconest is 50 IU per kg with a maximum of 4200 IU to be administered as a slow intravenous injection over approximately 5 minutes. • If the attack symptoms persist, an additional (second) dose can be administered at the recommended dose level. Do not exceed 4200 IU per dose. • No more than two doses should be administered within a 24 hour period.

Monitoring: • Symptomatic improvement • Monitor for signs/symptoms of hypersensitivity reactions and thrombotic events.

Consider long-term prophylaxis for patients with HAE who experience ≥ one severe event per month or who are disabled more than five days per month OR if the patient has a history of previous airway compromise. Options include: 1. 17α-alkylated androgens (danazol, stanozolol if available, and oxandrolone): Generally treatment of choice for long-term preventative treatment. Contraindications include pregnancy, breastfeeding, significantly impaired renal/ hepatic function, etc (refer to package insert for complete list). See Milan or Budapest Protocols for dosing recommendations. Use in children should be undertaken only with great caution.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 69 of 91 Drug Prior Authorization Criteria 2. Antifibrinolytics (epsilon aminocaproic acid [Amicar®]): Less effective than androgens. Often reserved for patients who do not tolerate or in whom anabolic androgens are contraindicated. 3. Human C1 inhibitor (Cinryze®) replacement: May be necessary in patients in whom androgens are not effective (frequent angioedema attacks), not tolerated or contraindicated. Human C1 inhibitor prophylaxis is the safest prophylactic agent to use during pregnancy. Sabril® Candidates for Sabril® should meet ALL of the following criteria: (Vigabatrin) Infantile Spasms 1. Prescribed by a neurologist 2. Between the ages of 1 month to 2 years old. 3. Potential benefit must outweigh the potential risk of vision loss. 4. Must have vision tested to the extent possible depending on the age of the child at baseline before beginning treatment and at least every 3 months.

Refractory Complex Partial Seizures 1. Prescribed by a neurologist. 2. 18 years of age or older. 3. Tried and failed at least 2 other anticonvulsant agents. 4. Vigabatrin used as adjunct therapy. 5. Potential benefit must outweigh the potential risk of vision loss. 6. Must have vision tested at baseline before beginning treatment and at least every 3 months.

Initial Approval period: 3 months

Continued approval: • Approval renewed every 3 months for Refractory Complex Partial Seizures o Must provide updates on eye exams upon renewal. o Must show a substantial clinical benefit within 3 months of starting treatment in order to continue therapy. o Must show a substantial clinical benefit within 2-4 weeks of starting treatment in order to continue therapy.

Caution: • Peripheral visual field defect, the risk increases with higher doses and longer duration. • Should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefit outweighs the risk. • Renal impairment: CrCl greater than 50 to 80 mL/min, decrease dose by 25%; CrCl greater than 30 to 50 mL/min, decrease dose by 50%; CrCl greater than 10 to 30 mL/min, decrease dose by 75%

Monitoring: • Vision must be tested at baseline and every 3 months

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 70 of 91 Drug Prior Authorization Criteria • Worsening of depression, suicidal ideation, and abnormal changes in behavior

Special considerations: • FDA mandated Risk Evaluation and Mitigation Strategies (REMS) associated with Sabril®. • The medication is shipped directly to the patient. • Available only through a special restricted distribution program called SHARE, by calling 1- 888-45-SHARE. • Only prescribers and pharmacies registered with SHARE may prescribe and distribute Sabril®. • For infants the medication is usually taken for 6-9 months. Dosage is often reduced at this point to see if symptoms re-emerge. If so, the dosage is increased to previous levels. • Upon discontinuation, tapering of dose recommended

Dosing: • Infantile Spasms: Initial, 50 mg/kg/day ORALLY in 2 divided doses; titrate by 25 to 50 mg/kg/day increments every 3 days up to a MAX of 150 mg/kg/day • Refractory Complex Partial Seizures : Adjunct therapy: initial, 500 mg ORALLY twice daily; titrate total daily dose in 500-mg increments at weekly intervals to a MAX dose of 1500 mg twice daily

Ordering information: Sabril® is only available only through a special restricted distribution program called SHARE, by calling 1-888-45-SHARE. Only prescribers and pharmacies registered with SHARE may prescribe and distribute Sabril®. Important forms for the Sabril® Prescribing Process can be found at http://lundbeckshare.com/pg512_important_steps.aspx?utm_medium=Links&utm_source=www.sabr il.net&utm_content=/hcp/.

SGLT2 inhibitors: For non-preferred combination product: 1. Patient must meet criteria for DPP-4 inhibitor and SGLT2 inhibitor AND/OR Invokana™ 2. Separate prescriptions are required for ingredients in non-preferred combination products: (Canagliflozin)

Farxiga™ ***Note: In patients with clinical atherosclerotic cardiovascular disease (ASCVD) (includes (Dapagliflozin) acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial Steglatro™ revascularization, stroke, TIA, carotid stenosis ≥50%, or symptomatic peripheral arterial (Ertugliflozin) disease presumed to be of atherosclerotic origin) consider the use of empagliflozin Non-Covered (Jardiance) if additional medications are needed to achieve glucose control. combination products The non-preferred SGLT2 Inhibitor will be covered for current KP new start members who meet ALL (separate of the following criteria: prescriptions required for 1. Documented diagnosis of type 2 diabetes mellitus > 18 years of age ingredients in 2. A1c within 1% of goal in the past 3 months a. A1c goal < 7% for patients 18-64 years of age b. A1c goal of at least < 8% is acceptable for patients > 65 years of age, or for patients 18-64 years of age with a history of dementia, blindness, lower extremity *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 71 of 91 Drug Prior Authorization Criteria combination amputation, CKD 4/5, ESRD, cardiomyopathy/CHF, or history of cardiovascular products): disease (MI, CABG, percutaneous coronary intervention, angina, thoracoabdominal aneurysm, carotid stenosis, renal atherosclerosis, peripheral vascular disease) Glyxambi (empagliflozin and 3. Failed to obtain adequate glycemic control on combination therapy with: linagliptan) a. Metformin at least 1000 mg per day (adherence> 80% for 3 months) unless patient is not a candidate for metformin AND Invokamet, XR *Note: If GI intolerance on metformin IR, must complete a trial metformin (Canagliflozin and SR 500mg 1 tab po daily for 7 days then titrate to metformin SR 500mg 1 metformin) tab po bid as tolerated b. Sulfonylurea (adherence > 80% for 3 months) unless the patient is not a candidate Xigduo XR for sulfonylurea therapy or the patient is already on multiple daily insulin injections (Dapagliflozin and (i.e prandial insulin) AND metformin) c. Titration of insulin: For non-obese patients (BMI ≤29) an insulin dose of 0.4-0.6 units/kg/day and for obese patients (BMI ≥30) an insulin dose of 0.8 – 1.2 Segluromet units/kg/day) OR (Ertugliflozin and i. The SGLT-2 may be initiated prior to insulin trial if patient meets ONE of the metformin) following criteria: 1. Commercial driver’s licenses OR Steglujan 2. Significant weight gain (≥ 5% increase in body weight after 6 (Ertugliflozin and months of starting a diabetes agent) OR sitagliptin) 3. Prescriber indicates promotion of weight loss is a major consideration and this patients HgbA1c is close to target HbgA1c level is close to target (<8) (For patients with BMI 35 and above).

4. Patient is not currently on an agent in any of the following classes: GLP-1 RAs, SGLT2 inhibitor, and DPP-4 inhibitors 5. Documented trial, intolerance or contraindication to Jardiance, if request is for non-preferred SGLT-2 Inhibitor. 6. Documented trial or unable to tolerate Jardiance, if request is for non-preferred SGLT2 inhibitor.

Initial approval period: 5 months. Patient must obtain HbgA1c after 3 months of initiating therapy (this lab should be ordered when initiating therapy).

Note: Starting dose is Jardiance 25mg ½ tablet daily. Dose response curves do not show much difference between 10mg vs. 25mg.

Continued approval: 1 year, based on: 1. Adherence (> 80%) to diabetic regimen AND 2. Documented HgbA1c lowering of 0.5% from initial A1c to result in a sustainedA1c of ≤7.9%% (must be performed within the past 3-6 months).

Members new to KP taking a non-preferred SGLT2 Inhibitor prior to enrollment:

Will be covered for those who meet ALL of the following criteria: 1. Documented diagnosis of type 2 diabetes mellitus AND

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 72 of 91 Drug Prior Authorization Criteria 2. Metformin dose at least 1000mg per day unless patient is not a candidate for metformin AND Note: If GI intolerance on metformin IR, must complete a trial metformin SR 500mg 1 tab po daily for 7 days then titrate to metformin SR 500mg 1 tab po bid as tolerated 3. Adherence to sulfonylurea (unless patient is not a candidate or cannot tolerate AND 4. A1c < 8% within 30 days AND 5. Patient is not currently on an agent in any of the following classes: GLP-1 RAs, SGLT2 inhibitor, and DPP-4 inhibitors AND 6. Documented trial, intolerance or contraindication to Jardiance, if request is for non-preferred SGLT-2 Inhibitor

Reasons for non-coverage: 1. Type 1 diabetes mellitus 2. Treatment of diabetic ketoacidosis 3. Pediatric patients (<18 years old) 4. Severe renal impairment, end-stage renal disease, or dialysis (not recommended to initiate Invokana™ in patients with an eGFR < 45 mL/min for or initiate Farxiga™ in patients with an eGFR < 60 mL/min) 5. Active bladder cancer for Farxiga™

Somavert® Candidates for treatment with Somavert® should meet ALL the following criteria: (Pegvisomant) 1. Documented diagnosis of acromegaly 2. Prescribed by an endocrinologist 3. Documented inadequate response or not a candidate for surgery or radiation for the management for acromegaly 4. Documented inadequate response or unable to tolerate Sandostatin® (octreotide) OR Somatuline® (lanreotide)

Initial Approval: 6 months

Continued Approval: 12 months if there is documented evidence of improvement in disease symptoms or stabilization of disease state and liver enzymes have been assessed and recommendation to continue treatment aligns with prescribing information for continuation of treatment based on results of liver tests

Dosage and Administration • A loading dose of 40 mg of Somavert® should be administered subcutaneously under physician supervision • Maintenance dose: 10 mg subcutaneously once daily • Doses may be adjusted by 5 mg increments in 4- to 6-week intervals based on IGF-I concentrations (maximum maintenance dose: 30 mg/day) • Somavert® may be given in the thigh, buttocks, upper arm, or abdomen; the site of SC injections should be rotated daily to help prevent lipohypertrophy

Monitoring:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 73 of 91 Drug Prior Authorization Criteria • GH-secreting tumor size • Serum glucose • Signs and symptoms of growth hormone deficiency • Serum IGF-I (every 4-6 weeks after initial dose and dosage change, every 6 months when normalized • Liver function tests at monthly intervals during the first 6 months of treatment, quarterly for the next 6 months, and then semi-annually for the next year

Ordering information: Somavert® is furnished by the KP Speicalty Pharmacy (KP SP) in Daly City, California. Fax the Somavert® Order Form to KP SP (650-301-5790). The Somavert® Order Form can be found on the KP SP Website. Sovaldi Sovaldi is a non-preferred treatment agent at Kaiser Permanente. Please refer all requests to (sofosbuvir) internal KP Hepatology or Infectious Disease. Spinraza Candidates for treatment with Spinraza should meet ALL the following criteria:

(Nusinersen) 1. Treatment of spinal muscular atrophy (SMA) with documented SMN1 deletion, or 5q SMA homozygous gene deletion, homozygous mutation, or compound heterozygote (Confirmation of appropriate testing by a geneticist is required) 2. Prescribed by Pediatric Neurology, Adult Neurology, Or Physical Medicine and Rehabilitation 3. Must be administered by a provider capable of intrathecal medication administration 4. Must be 21 years of age or younger; Patients age 16 to 21 years without documented objective evidence of progression of weakness during the prior two years should be reviewed by an Interregional Consultative Physician Panel prior to treatment initiation. a. If Interregional Consultative physician panel required, Send to Pharmacy Consult Service for review 5. Baseline Documentation in Medical record: CBC, PT/PTT, urinalysis within 1 week prior to initiation and prior to each dose 6. Baseline Documentation in Medical Record: Function assessment (HINE-2, CHOP INTEND, HFMSE, ULM, 6MWT) 7. Baseline Documentation in Medical record: Spine evaluation to assess ease of lumbar puncture entry, AND Risk assessment for Procedure (Objective respiratory testing), and QOL test (e.g. PedsQL or alternative QOL test for adults)

Reasons for Non-Coverage: • Age > 21 years. There is no evidence that nusinersen will benefit adults with SMA. Treatment in patients older than 21 years is not recommended outside of a clinical trial. • Permanent invasive ventilation or tracheostomy • Dependent on invasive or non-invasive ventilation during waking hours each day • Contraindication to lumbar puncture

Initial Approval: 4 Months

Continued Approval: 12 Months with documentation of follow-up assessments (See below):

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 74 of 91 Drug Prior Authorization Criteria

Criteria for Discontinuation: • Non-adherence to follow-up assessments o Descriptive function assessment o Specific motor function assessments described below based on patient age and ambulation status. Video documentation is recommended if possible. May be performed by a physical therapist or specialist in pediatric neurology, neurology, or PM&R . Infants: HINE-2 or CHOP INTEND . Children, Adolescents: HFMSE and ULM . All non-ambulatory: Upper limb module . All ambulatory: 6MWT . All Patients: QOL Test (PedsQL or alternative QOL test for adults), pulmonary risk evaluation with PFTs if able • Permanent invasive ventilation or tracheostomy • Dependent on invasive or non-invasive ventilation during waking hours each day • Loss of function or progressive weakness (Physical and/or pulmonary

Recommended Dosing: 12 mg (5 ml) intrathecally as room temperature bolus injection over 1-3 minutes after removing 5 ml of CSF. Initiate with 4 loading doses; the first three loading doses should be administered at 14-day intervals; the 4th loading dose should be administered 30 days after the 3rd dose; a maintenance dose should be administered one every 4 months thereafter. Optional alternate (off-label) dosing regimen for later-onset SMA (symptom onset age> 6 months): Initiate with the first dose at Day 1 and subsequent doses at Day 30 (1 month), Day 90 (3 months), and Day 270 (9 months); a maintenance dose should be administered once every 6 months thereafter. Supprelin® LA Candidates for Supprelin® LA should meet ALL of the following criteria: (Histrelin) implant 1. Diagnosis of central precocious puberty confirmed by ALL of the following: a. measurement of blood concentrations of total sex steroids (estrogens/testosterone) b. measurement of LH and FSH after stimulation with a GnRH analog c. assessment of bone age vs. chronological age 2. Failed (failure defined as the inability to suppress physical signs of puberty), intolerant, or allergic to Lupron Depot® 3. 2 years or older

Approval Duration: 1 year

Dosing: • Children ≥2 years: 50 mg implant surgically inserted every 12 months. Discontinue at the appropriate time for the onset of puberty.

Monitoring: • LH, FSH, estradiol, or testosterone (after 1 month then every 6 months); height, bone age (every 6-12 months); tanner staging

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 75 of 91 Drug Prior Authorization Criteria Symdeko™ Candidates for Symdeko™ should meet ALL of the following criteria: (tezacaftor/iva- caftor) 1. Confirmed diagnosis of cystic fibrosis (CF) 2. Prescribed by a pulmonologist 3. Age 12 years or older 4. Homozygous for F508del mutation OR 5. At least one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Symdeko:

6. Patient is not currently taking a strong CYP3A4 Inducer (e.g., rifampin, St. John’s wort, rifabutin, phenobarbital, carbamazepine, and phenytoin)

Initial Approval: 6 months

Continued Approval: 12 months if: • Patient has documented evidence of response to therapy (e.g. improvement or stable ppFEV1, improvement in BMI, decrease in pulmonary exacerbations) AND • ALT/AST levels have been checked within the last 3 months (ALT/AST should be monitored at baseline, every three months for one year, then once yearly thereafter). • In the event of significant elevations of transaminases, e.g., patients with ALT or AST > 5 X upper limit of normal or ALT or AST > 3x upper limit of normal with concomitant bilirubin > 2x upper limit of normal, therapy should be temporarily discontinued. Following the resolution of transaminase elevations consider the benefits and risks of resuming treatment.

Dosing and Administration: • Adults and pediatric patients age 12 years and older: one tablet (containing tezacaftor 100 mg/ivacaftor 150 mg) in the morning and one tablet (containing ivacaftor 150 mg) in the evening, approximately 12 hours apart. Symdeko should be taken with fat-containing food. • Reduce dose in patients with moderate and severe hepatic impairment. • Reduce dose when co-administered with drugs that are moderate or strong CYP3A inhibitors.

Ordering information: Symdeko™ is available through the KP Specialty Pharmacy. Prescribers must complete the KP Specialty Pharmacy Symdeko™ Drug Order Form at http://pharmacyprod.appl.kp.org/kp- cms/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Object=1787&nodeVal ue=113# and fax it to KP-Specialty Pharmacy (1-650-301-5790). Symlin® Candidates for Symlin® should meet ALL of the following criteria: (Pramlintide) 1. Prescriber must be an Endocrinologist AND Type 1 diabetics

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 76 of 91 Drug Prior Authorization Criteria 2. Using both basal insulin and short-acting insulin AND 3. Requires three or more insulin injections daily, OR using an insulin pump

Type 2 diabetics 2. Receiving maximum tolerated doses of metformin, unless the patient is not a candidate for metformin therapy, AND 3. Using both basal insulin and short-acting insulin, AND 4. Requires three or more insulin injections daily OR using an insulin pump AND 5. Failure to achieve adequate glycemic control despite individualized insulin management, defined as: i. A1C level is greater than 7% and less than 9%, OR ii. Marked day-to-day variability in glucose levels (based on review of self-monitoring blood glucose levels)

Reasons for Non-Coverage: Symlin® is not covered for patients meeting any of the following criteria: • Poor compliance with current insulin regimen • Poor compliance with prescribed self-blood glucose monitoring • An A1C greater than 9% • Recurrent severe hypoglycemia requiring assistance during the previous 6 months • Presence of hypoglycemia unawareness • Confirmed diagnosis of gastroparesis • Need for medications that stimulate GI motility • Pediatric patients (less than 18 years of age) • Concurrent use with other oral antidiabetic medications (except metformin and sulfonylureas) or drugs that alter gastrointestinal motility

Initial approval period: 6 months

Continued approval: 1 year, based on review of compliance to therapy and documented improved glycemic control as evidenced by A1C lowering from pretreatment level Tecfidera™ Tecfidera should be reserved for treatment of relapsing forms of multiple sclerosis in patients with (Dimethyl moderate disease activity who have contraindications or severe intolerance to preferred therapies or fumarate) have severe injection site reactions not responsive to conservative measures.

Candidates for treatment with Tecfidera™ should meet ALL the following criteria:

1. 18 years of age or older 2. Documented diagnosis of relapsing-remitting multiple sclerosis (MS) 3. Prescribed by a neurologist 4. Tecfidera is prescribed for use as monotherapy 5. CBC within the past 6 months shows normal WBC and lymphocyte counts

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 77 of 91 Drug Prior Authorization Criteria 6. For females of child bearing age (12-50 years of age), a baseline negative pregnancy test within the past month AND either a prescription for birth control (IUD or other contraceptive) or documentation of the patient declining contraception and being counseled of the potential risk of pregnancy. 7. Patient is unable to master self-injection technique and lacks a caregiver who can perform injections OR 8. Patient has a history of severe injection site reactions not responsive to conservative measures while on injectable agents for MS (eg: lipoatrophy or skin necrosis) OR 9. Documented inadequate response, severe intolerance or relative contraindication to one interferon therapy (i.e., Avonex®, Betaseron®, Extavia® [preferred interferon],Plegridy® or Rebif®)* AND glatiramer acetate (Glatopa or Copaxone®)* *NOTE: Injection fatigue or fear of needles is not a reason for intolerance or inadequate response.

Reasons for non-coverage:

Tecfidera should NOT be used in patients with any of the following:

1. Lymphocyte count < 0.5 x 109/L for over 6 months 2. Signs and symptoms of serious infection 3. JCV antibody positive and previously treated with Tysabri

Initial approval period: 1 year

Continued approval for treatment with Tecfidera should meet ALL the following criteria:

• Documented beneficial effect from therapy during neurology follow up • CBC with differential including lymphocyte count obtained 6 months after initiation of treatment then at least once every 12 months • Lymphocyte count > 0.5 x 109/L • No signs and symptoms of serious infection • Continued approval period: 1 year

Dosage and Administration

1. Starting dose, for days 1-7: 120 mg orally twice a day 2. Maintenance dose, after 7 days: 240 mg orally twice a day

Ordering information:

Tecfidera™ is available through the KP specialty pharmacy. If approved for coverage, prescribers must complete the KP Specialty Pharmacy form Tecfidera™ Prescription Order Form at http://pharmacy.kp.org/KPCMS/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Obj ect=1320&nodeValue=113 and fax it to KP-Specialty Pharmacy (1-650-301-5790).

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 78 of 91 Drug Prior Authorization Criteria Technivie® Technivie is a non-preferred treatment agent at Kaiser Permanente. Please refer all requests to (Ombitasvir/parita internal KP Hepatology or Infectious Disease. previr/ ritonavir) Tysabri® Candidates for Tysabri® should meet ALL of the following criteria: (Natalizumab) Testing for anti-JC virus (JCV) antibodies is recommended in patients considering or receiving Tysabri®

For Multiple Sclerosis: Tysabri should be reserved for treatment of patients with relapsing forms of multiple sclerosis exhibiting high-disease activity or prognostic factors for early progression to secondary progressive multiple sclerosis.

1. Patient and Physician are enrolled in the Tysabri TOUCH program *NOTE: For information on how to enroll in the MS TOUCH program please visit https://www.touchprogram.com/TTP/tolTOUCHEnroll.jsp 2. Diagnosis of relapsing-remitting multiple sclerosis (RRMS) or progressive-relapsing MS (PRMS) 3. Prescriber is a Neurologist 4. Tysabri is prescribed for use as monotherapy for treatment of multiple sclerosis 5. Documented JC virus antibody test within 3 months 6. For females of child bearing age (12-50 years of age), a baseline negative pregnancy test within the past month AND either a prescription for birth control (IUD or other contraceptive) or documentation of the patient declining contraception and being counseled of the potential risk of pregnancy. 7. Patient has already started treatment with Tysabri (new member to KP) and needs to continue the therapy to avoid the risk of rebound disease OR 8. Documented inadequate response, contraindication, or intolerance to at least ONE interferon therapy (Avonex®, Betaseron®, Extavia®[preferred interferon], Plegridy® or Rebif®)*, glatiramer acetate (Glatopa or Copaxone), Gilenya, Aubagio (if moderate disease) and Tecfidera (if moderate disease) OR 9. Documented evidence of high-risk features for early progression to secondary-progressive MS (see Table 1)

*NOTE: Injection fatigue or fear of needles is not a reason for intolerance or inadequate response.

Table 1: High-risk features for early progression History of MS relapse with Lesion load Duration Symptom type Timing / frequency ≥ 30 days and Sphincter OR ≥ 3 relapses in the After 1 yr of therapy, significant functional Motor OR first 2 years after ≥ 3 new or enlarging limitations, besides Cerebellar (ataxia or diagnosis OR T2 lesions, ongoing sensory tremor) continued gad+ symptoms lesions, or diffusion-

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 79 of 91 Drug Prior Authorization Criteria Average of ≥ 1 restricted imaging relapse/ year over 2 lesions over a 1 yr to 3 years OR period OR After 6 months of ≥ 5 lesions over 2 new therapy, years OR relapse in the next 6 ≥ 1 cord lesion months

Reasons for non-coverage:

Tysabri should not be used in patients with any of the following: 1. Diagnosis of primary progressive MS or secondary progressive MS with no clinical or MRI evidence of relapses 2. Current diagnosis or history of PML 3. Patient is receiving concurrent disease-modifying treatments for MS 4. JCV antibody positive and immunosuppression (due to HIV, AIDS, leukemia, lymphoma or organ transplantation) 5. JCV antibody positive and history of antineoplastics or immunosuppressants (eg: adalimumab, alefacept alemtuzumab, anakinra, azathioprine, cladribine, cyclophosphamide, cyclosporine, daclizumab, efalizumab, etanercept, fludarabine phosphate, infliximab, intravenous immunoglobulin, leflunomide, mercaptopurine, methotrexate, mitoxantrone, mycophenolate mofetil, mycophenolic acid, pemetrexed, rituximab, trastuzumab)

Initial Approval: 3 months.

Continued approval: 1 year based on the following: • Documented efficacy from the prescribing physician and continued registration with the TOUCH program • Patients with a previous negative assay for anti-JCV antibodies must be retested annually to be considered for continued approval. • Patients with a previous positive assay for anti-JCV antibodies no longer need to be retested • Patients with a previous positive assay for anti-JCV antibodies no longer need to be retested • Patient has already started treatment with Tysabri (new member to KP) and needs to continue the therapy to avoid the risk of rebound disease

For Crohn’s Disease: 1. Patient and Physician are enrolled in the Tysabri TOUCH program *NOTE: For information on how to enroll in the TOUCH program please visit https://www.touchprogram.com/TTP/tolTOUCHEnroll.jsp 2. Prescriber is a gastroenterologist 3. Diagnosis of moderate to severe active Crohn’s disease and documented evidence of inflammation despite therapy with ONE medication from the following classes: a. 5-ASA: mesalamine, sulfasalazine b. Immunosuppressants: azathioprine, 6-mercaptopurine c. Corticosteroids *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 80 of 91 Drug Prior Authorization Criteria d. TNF-α inhibitor: infliximab (Remicade), adalimumab (Humira), or certolizumab (Cimzia) 4. Documented baseline and annual JC virus antibody test within 3 months of review 5. For females of child bearing age (12-50 years of age), a baseline negative pregnancy test within the past month AND either a prescription for birth control (IUD or other contraceptive) or documentation of the patient declining contraception and being counseled of the potential risk of pregnancy. 6. Documented baseline and annual liver enzyme labs within normal limits

Reasons for non-coverage:

Tysabri should not be used in patients with any of the following: 1. Current diagnosis or history of PML 2. JCV antibody positive and immunosuppression (due to HIV, AIDS, leukemia, lymphoma or organ transplantation) 3. Patient is receiving concurrent treatment with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or TNF-α inhibitors 4. After initial 6-month steroid taper, use of additional steroids for > 3 months in a calendar year for disease control 5. Tysabri should be discontinued in patients who develop herpes encephalitis and meningitis or significant liver injury (from elevated liver transaminases to liver failure requiring transplant)

Crohn’s Disease: Initial Approval: 3 months. Tysabri should be discontinued if clinical benefit has not been shown after 12 weeks.

Continued approval: 1. For patients receiving a therapeutic benefit but still receiving oral corticosteroids, reauthorization will only be granted for 3 additional months. If at the end of this time the patient cannot be tapered off oral corticosteroids Tysabri will not be reauthorized. 2. For patients receiving therapeutic benefit and weaned off oral corticosteroids within 6 months, reauthorization may be granted for up to one year with documented efficacy from the prescribing physician and compliance with the TOUCH program. 3. Patients with a previous negative assay for anti-JCV antibodies must be retested annually to be considered for continued approval. 4. Treatment duration greater than 2 years increases the risk of PML. Documented assessment and discussion of alternatives with patients after 2 years of treatment is required for continued approval.

Dosage and Administration: Multiple sclerosis 1. Tysabri should be administered to multiple sclerosis patients once every 4 weeks in a dose of 300 mg diluted in 100 ml Normal Saline given intravenously over about one hour. Tysabri should NOT be given as a bolus or push. Crohn’s Disease

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 81 of 91 Drug Prior Authorization Criteria 2. Tysabri should be given 300 mg infused over 1 hour every 4 weeks; discontinue if therapeutic benefit is not observed within initial 12 weeks of therapy

Multiple sclerosis and Crohn’s Disease: 3. Tysabri should only be administered in an infusion center with adequate facilities for treating a hypersensitivity or infusion-related reaction. 4. Tysabri should be used with caution in patients who are receiving chronic immunosuppressant therapy, other immunomodulatory drugs, or are significantly immunocompromised for any reason.

Ordering information: Prescribers must be enrolled TOUCH Prescribing Program. For information on how to enroll in the program, please visit https://www.touchprogram.com/TTP/tolTOUCHEnroll.jsp#Prescribers. If approved for coverage, Tysabri® is available through the KP Specialty Pharmacy. Prescribers must complete the KP Specialty Pharmacy Tysabri® Order Form at http://pharmacy.kp.org/Kp- CMS/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Object=1119&nodeValue=113 and fax it to KP-SP (1-650-301-5790). Viberzi® Candidates for Viberzi should meet ALL criteria below: (Eluxadoline) 1. 18 years of age or older 2. Documented diagnosis of moderate to severe Irritable Bowel Syndrome with diarrhea (IBS-D) 3. Prescribed by a gastroenterologist 4. Documented contraindication or previous trial and/or intolerance to at least two of the following. If >65 years old, trial of one therapy is adequate: • Anti-diarrheal (i.e., loperamide, diphenoxylate/atropine*) • Tricyclic antidepressant* (i.e., amitriptyline, desipramine, imipramine) • Antispasmodic* (i.e., dicyclomine, chlordiazepoxide/clidinium, hyoscyamine) • Bile acid sequestrant (i.e., cholestyramine, colestipol, colesevelam) 5. Documented contraindication or previous trial and/or intolerance to Xifaxan (rifaximin)

* Beer’s Criteria; NOT recommended if >65 years old.

Reasons for non-coverage: Viberzi should not be used in patients with any of the following:

1. History of cholecystectomy 2. Known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction 3. Alcoholism, alcohol abuse, alcohol addiction, or more than 3 alcoholic beverages/day consumed 4. A history of pancreatitis or structural disease of the pancreas including known or suspected pancreatic duct obstruction 5. Severe hepatic impairment (Child-Pugh Class C) 6. Severe constipation or sequelae from constipation or known or suspected mechanical gastrointestinal obstruction 7. Chronic use of medications that can cause constipation (i.e., antidiarrheals, alosetron, opioids, tricyclic antidepressants, antispasmodics, bile acid sequestrants). Loperamide may be used with Viberzi for acute management of severe diarrhea.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 82 of 91 Drug Prior Authorization Criteria Initial approval period: 6 months

Continued approval: 12 months

Approved if patient meets ALL criteria below:

1. Beneficial effect documented during gastroenterology follow-up as demonstrated by at least one of the following: (1) improvement in abdominal pain, or (2) improvement in stool frequency and consistency 2. Patient tolerating treatment without serious adverse effects such as new or worsening abdominal pain, with or without pancreatic enzyme elevations or severe constipation 3. Patient does not meet criteria above for “reasons for non-coverage”

Dosing and administration:

• Recommended dosage in adults is 100 mg twice daily taken with food. • Recommended dosage is 75 mg twice daily taken with food for patients: o Unable to tolerate the 100 mg dose o Taking concomitant OATP1B1 inhibitors (e.g. cyclosporine, gemfibrozil, antiretrovirals (atazanavir, lopinavir, ritonavir, saquinavir, tipranavir), rifampin, eltrombopag) o Mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment Viekira Pak® Viekira Pak and Viekira XR are non-preferred treatment agents at Kaiser Permanente. Please refer Viekira XR® all requests to internal KP Hepatology or Infectious Disease. (Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir) VMAT2 Candidates for treatment should meet the following criteria: Inhibitors: 11. Documented diagnosis of chorea associated with Huntington’s disease or tardive dyskinesia Xenazine® 12. Prescribed by a neurologist or psychiatrist (Tetrabenazine) 13. Patient is 18 years or older 14. For Tardive Dyskinesia, documented inadequate response, intolerance or contraindication to Austedo® at least 2 of the agents listed below: (deute- a. Clonazepam trabenazine) b. Quetiapine or clozapine

c. Amantadine d. Tetrabenazine (for Austedo coverage) 15. For Huntington’s Chorea, documented inadequate response, intolerance, or contraindication to riluzole (Rilutek®) AND amantadine

Reasons for non-coverage: • Patients who are suicidal, or who have depression which is untreated or undertreated • Patients with impaired hepatic function

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 83 of 91 Drug Prior Authorization Criteria • Coadministration with or within 14 days of discontinuing monoamine oxidase inhibitors (MAOIs) [ i.e. isocarboxazid, phenelzine, selegiline] • Coadministration with or within 20 days of discontinuing reserpine • Patients taking other VMAT2 Inhibitors [tetrabenazine (Xenazine), valbenazine (Ingrezza) or deutetrabenazine (Austedo) • Patients with congenital long QT syndrome or with arrhythmias associated with prolonged QT interval.

Initial Approval: 3 months

Continued Approval: 12 months if there is documented evidence of improvement in disease symptoms or stabilization of disease state. Discontinue therapy if no improvement over prior therapy after 3 months.

Dosage and Administration Xenazine (tetrabenazine): Chorea associated with Huntington’s disease • Initial: 12.5 mg once daily, may increase to 12.5 mg twice daily after 1 week • Maintenance: May be increased by 12.5 mg/day at weekly intervals; doses >37.5 mg/day should be divided into 3 doses (maximum single dose: 25 mg) Tardive Dyskinesia (off-label): • Initial: 50 mg/day in divided doses; if needed, may increase daily dose by 50 mg every two weeks up to maximum of 150 mg/day in divided doses.

Austedo (deutetrabenazine): Chorea associated with Huntington’s disease • Initial: 6 mg once daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day; administer in two divided doses if total daily dose ≥12 mg; maximum recommended dose: 48 mg/day. Tardive Dyskinesia • 6 mg twice daily; may increase dose weekly based on response and tolerability in increments of 6 mg/day. Administer in two divided doses if total daily dose ≥12 mg; maximum recommended dose: 48 mg/day.

Vosevi Candidates for Vosevi should meet ALL the following criteria: (sofosbuvir/velpat asvir/voxilaprevir) 1. Is the medication prescribed by a Gastroenterologist or Infectious Disease specialist? If yes, go to #2 If No, patient does NOT meet criteria for Vosevi; go to #5

2. Does the patient have a documented Hepatitis C Virus RNA PCR quantitative in previous 6 months? If yes, go to # 3 If No, patient does NOT meet criteria for Vosevi: patient needs updated viral load, go to #5

3. Has the patient failed treatment with a NS5A-Containing Regimen? If Yes, go to #4 *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 84 of 91 Drug Prior Authorization Criteria If No, patient does NOT meet criteria for Vosevi; go to #5

4. Does the patient have an eGFR > 30 ml/min/1.73 m2 If yes, Patient meets criteria for Vosevi for 12 weeks If No, Go to # 5

5. Has patient been reviewed by the KP Hepatology Clinic OR KP Infectious Disease service? If yes, continue with approval If No, please contact Lisa Woolard, PharmD at 770-677-5869

Approval: 12 weeks total duration

GI or ID specialist will call after start of therapy if patient needs to stop or change therapy:

Dosage and Administration: • One tablet (400 mg of sofosbuvir/100 mg of velpatasvir/100 mg of voxilaprevir) taken orally once daily with or without food. Xgeva® Candidates for Xgeva™ should meet ALL of the following criteria: (Denosumab) 1. Diagnosis of bone metastases from prostate cancer OR 2. Diagnosis of bone metastases from solid tumors OTHER THAN Prostate a. A therapeutic trial and clinical failure with zoledronic acid (Zometa®) OR documented renal dysfunction (CrCl< 30 ml/min) Note: Clinical failure defined as development of new skeletal related event (SRE) while receiving treatment with zolendronic acid for at least 3 months. 3. Must be prescribed by a hematologist or oncologist 4. Calcium levels have been checked and any pre-existing hypocalcemia has been corrected 5. Patient has had a baseline dental exam prior to initiating denosumab therapy

Reasons for non-coverage: • Treatment of skeletal-related events in patients with multiple myleoma • Hypocalcemia • Pediatric patients (<18 years old) • Non-FDA approved indications

Initial Approval: 6 months Continued Approval: 12 months if patient has documented clinical benefit from medication and no reported adverse events to Xgeva Use caution in the following patients: • Pregnant/nursing women (Pregnancy Category D)

Dosing: • Inject 120 mg subcutaneously every four weeks

Xiaflex™ Candidates for Xiaflex™ should meet ALL of the following criteria: (Collagenase Xiaflex™ is only available through the Xiaflex™ Experience Program Clostridium Histolticum) Use of Xiaflex in patient with Dupuytren’s contracture:

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 85 of 91 Drug Prior Authorization Criteria 1. Documented diagnosis of Dupuytren’s contracture with a palpable cord 2. Must be prescribed and administered by a hand surgeon, plastic surgeon, orthopedic surgeon or rheumatologist 3. Documentation of training in Xialfex™ injections must be provided by the prescriber 4. A positive “table top test” – defined as the inability to simultaneously place the affected finger and palm flat against a table top 5. Documented contracture of at least 20 degrees flexion for a metacarpophalangeal joint contracture or at least 20 degrees flexion for a proximal interphalangeal joint contracture 6. Documentation that the flexion deformity results in functional limitations 7. Must be 18 years of age or older 8. Must not have had surgery on the primary joint within the past 90 days

Xiaflex™ will only be used on one cord at a time • Treatment of each cord should be undertaken in sequential order with only one cord receiving Xiaflex™ at a time

Use of Xiaflex in patient with Peyronie’s disease: 1. Documented diagnosis of Peyronie’s disease with a palpable plaque 2. Patient has curvature deformity for at least 30 degrees at the start of therapy 3. Must be prescribed by a Urologist 4. Documented Peyronie’s symptoms (penile pain, erectile dysfunction, etc)

Reason for non-coverage: • For the treatment of Peyronie’s plaques that involve the penile urethra

Initial approval: Dupuytren’s contracture: 3 months Peyronie’s disease: one treatment cycle (2 injections)

Continued approval: Dupuytren’s contracture: 6. Injection may be repeated up to a maximum of 3 sessions for cord at 4 week intervals if reduction in primary joint contracture is not 0-5 degrees of full extension 7. Patient must follow-up within 24 hours following an injection for finger extension procedure if a contracture persists in order to qualify for more injections Peyronie’s disease: • Re-authorization for another treatment cycle may be given if the curvature deformity is more than 15 degrees after previous treatment cycle or if prescribing physician indicates another treatment cycle is clinically indicated (maximum of 4 treatment cycles) • Patient must wait six weeks between treatment cycles

Dosage and Administration: Dupuytren’s contracture: *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 86 of 91 Drug Prior Authorization Criteria • The dose for Xiaflex™ is 0.58 mg per injection into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint, according to the injection procedure • Finger extension procedures may be performed approximately 24 hours after the injection in the event the cord has not spontaneously ruptured Peyronie’s disease: • A treatment cycle consists of two Xiaflex injection procedures and a penile modeling procedure. • Induce a penile erection and identify and mark the target area in the Peyronie’s plaque to be injected. • The penis should be in a flaccid state before injecting Xiaflex. Inject 0.58 mg Xiaflex into the target plaque once on each of two days, 1 to 3 days apart, according to the injection procedure. Perform a penile modeling procedure 1 to 3 days after the second injection of each treatment cycle.

Use caution in the following patientsCaution is advised in those receiving anticoagulation therapy, with the exception of low-dose aspirin (maximum 150 mg/day). Monitoring: • Patient must follow-up with provider within 24 hours following an injection for finger extension procedure Xolair® Candidates for Xolair® should meet ALL of the following criteria: (Omalizumab) injection Use of Xolair® in patients with moderate to severe persistent asthma: 1. Prescribed by a pulmonologist or allergy specialist

2. 6 years of age and older 3. Moderate to severe persistent asthma [based on criteria of the National Heart, Lung, and Blood Institute (NHLBIs) National Asthma Education and Prevention Program (NAEPP)] 4. Allergic asthma confirmed by positive skin testing or in vitro reactivity to a perennial aeroallergen 5. Baseline total IgE serum level from 30-700 international units/mL for patients 12 years and older OR between 30 and 1300 international units/ml for children 6 to 11 years. 6. Treatment failure* to aggressive trials of drug therapy: o Adults and adolescents 12 years and older: . High-dose inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) combination inhalers e.g. fluticasone 500 mcg/salmeterol 50 mcg (Advair Diskus) 1 puff twice daily) . If failure to the above drugs, trials of each of the following drugs should be added to the above therapy • Montelukast (generic Singulair): > 15 years: 10 mg orally daily (in the evening); 12-14 years: 5 mg orally (in the evening) • Tiotropium (Spiriva Respimat) 2.5 mcg: 1 puff once daily (>12 years) (off-label dosing) o Children 6 to 11 years: . High dose ICS in combination with a LABA plus montelukast o If a patient has been intermittently poorly controlled over a long period of time (at least one year in duration) and is experiencing steroid side effects despite aggressive drug therapy, then omalizumab could be considered. *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 87 of 91 Drug Prior Authorization Criteria *Treatment failure defined as one or more of the following: • Asthma exacerbations in the past 12 months requiring systemic corticosteroids • Short-acting beta-agonist use > 2 days/week (excluding pretreatment for exercise) • Nocturnal awakenings > 2 nights/month

Use of Xolair® in patients with chronic idiopathic urticaria: 1. Documented diagnosis of chronic idiopathic urticaria 2. 12 years of age or older 3. Prescribed by an allergy specialist or dermatologist 4. Tried and failed therapy for a minimum of 4 weeks on ALL of the following unless contraindicated: a. At least two different high-dose second generation H1-antihistamines (e.g. loratadine, cetirizine) 2 – 4 times normal dose daily dose b. Montelukast in combination with a high-dose second generation H1-antihistamine c. H2- antihistamines (e.g. famotidine, ranitidine) in combination with a high-dose second generation H1- antihistamine d. Anti-inflammatory agent (e.g. dapsone, hydroxychloroquine, or sulfasalazine) OR an immunosuppressant agent (e.g. cyclosporine, mycophenolate) in combination with a high-dose second generation antihistamine

Reasons for non-coverage: • History of adverse reaction to omalizumab or any of its ingredients • Acute asthma exacerbation within the previous two weeks of requiring any of the following: initiation of systemic corticosteroids, increased doses of systemic corticosteroids from baseline, doubling of inhaled corticosteroids, emergency room visit, or hospitalization. • Acute flare of significant systemic disease (infection, hematologic, renal, hepatic, cardiovascular diseases, or gastrointestinal diseases), or a recent hospitalization because of their disease within the previous two months.

Initial Approval: 3 months

Continued Approval: 12 months if the patient has experienced any of the following: Moderate to severe persistent asthma: • Reduction in the frequency of asthma exacerbations and reduction in the use of rescue medications or inhaled corticosteroids. • Reevaluate asthma control at one, three, and six-month intervals or as necessary and reassess the need for continued therapy based on the patient’s disease severity and level of asthma control. There is limited data regarding the safety of using omalizumab long term.

Chronic idiopathic urticaria: • Reduction in the frequency of symptoms (wheals, pruritus).

Dosage and administration: Moderate to severe persistent asthma: • Subcutaneously: 75 to 375 mg every 2 or 4 weeks. Dose and frequency based on body weight and pretreatment total IgE serum levels. Dosing should be adjusted during therapy for significant changes in body weight.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 88 of 91 Drug Prior Authorization Criteria Chronic idiopathic urticaria: Subcutaneously: 150 or 300 mg every 4 weeks. Dosing is not dependent on serum IgE (free or total) level or body weight.

Monitoring: • Monitor the patient for hypersensitivity reactions approximately 2 hours after the first three injections, and for 30 minutes after the subsequent injections. • Omalizumab should be discontinued if a severe hypersensitivity reaction occurs. • Moderate to severe persistent asthma: o FEV1, peak flow, and/or other pulmonary function tests o Asthma signs and symptoms including wheezing, chest tightness, coughing, shortness of breath o Frequency of administration of rescue medication (short-acting beta2-agonist, albuterol) • Chronic idiopathic urticaria: o Symptoms: wheals, pruritus Zavesca Candidates for treatment with Zavesca should meet ALL the following criteria: (Miglustat) 1. Documented diagnosis of Type 1 Gaucher’s Disease 2. Patient is symptomatic (i.e. radiologic evidence of skeletal disease, platelet count <60,000 microL, liver >2.5 times normal size, spleen > 15 times normal size) 3. 18 years of age or older 4. Patient has been evaluated by a Geneticist 5. Tried and failed or unable to tolerate enzyme replacement therapy (Cerezyme, Vpriv, Elelyso) enzyme replacement therapy for at least 6 months. 6. Tried and failed or unable to tolerate eliglustat (Cerdelga)

Initial approval period: 6 months

Continued approval: 12 months if patient is responding to treatment (improving platelet count, decreased hepatomegaly and splenomegaly)

Monitoring: • Neurologic evaluations baseline and repeated every 6 months

Dosing and Administration: • Recommended dosage is 100 mg administered orally three times a day at regular intervals • May reduce dosage to 100 mg once or twice a day in some patients due to tremor or diarrhea

Ordering information: Zavesca is only dispensed by CuraScript specialty pharmacy (Fax: 888-773-7386). For more information, visit http://pharmacy.kp.org/Kp- CMS/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Object=1128&nodeValue=113 Zepatier® Candidates for Zepatier® should meet ALL of the following criteria: (Elbasvir and Grazoprevir) 1. Is the medication prescribed by a Gastroenterologist or Infectious Disease specialist?

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 89 of 91 Drug Prior Authorization Criteria If yes, go to #2 If no, patient does NOT meet criteria for Zepatier; go to #7

2. Has the patient previously been treated with Zepatier? If yes, patient does NOT meet criteria for Zepatier; go to #7 If no, go to #3

3. Does the patient have a documented Hepatitis C Virus RNA PCR quantitative in the previous 90 days? If yes, go to #4 If no, patient does NOT meet criteria for Zepatier; go to #7

4. Does the patient have a eGFR<30 ml/min/1.73 m2 or is on hemodialysis? If yes, go to #5 If no, patient does NOT meet criteria for Zepatier; go to #7

5. Does the patient have decompensated cirrhosis (moderate or severe hepatic impairment, Child- Turcotte-Pugh (CTP) Class B or C)?

If yes, patient does NOT meet criteria for Zepatier; go to #7 If no, go to #6

6. Does the patient have genotype 1 or 4? If yes, the patient QUALIFIES for 12 weeks of Zepatier If no, patient does NOT qualify for Zepatier

7. If prescribed by an external provider, has PCS contacted the KP Hepatology clinic for internal KP physician review? If yes, continue with approval If no, please contact Lisa Woolard, PharmD at 770-677-5869

Initial Approval: 14 days

Continued Approval/Established Duration of Treatment: GI or ID specialist will call after start of therapy if patient needs to stop or change therapy duration. • For Genotype 1 and genotype 4: 12 weeks total duration

Dosage and Administration: • Recommended dose: one tablet (100 mg of grazoprevir and 50mg of elbasvir) taken orally once daily with or without food

Monitoring: • Serum HCV-RNA at baseline, weeks 4, 8, 12, during treatment follow up, and when clinically indicated

Dispensing information: *Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 90 of 91 Drug Prior Authorization Criteria Must be dispensed at Glenlake Pharmacy with an applicable quantity limit.

*Because the Medicare Part D formulary does not allow prior authorization or criteria restrictions on medications, this document applies to the Commercial, Triple Tier, and Multi-Choice formularies.

CONFIDENTIAL: FOR INTERNAL KAISER PERMANENTE USE ONLY Last Revised: August 22, 2018 Page 91 of 91