Prior Authorization Medications Requiring Review – Criteria For

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.

Brand Name and/or Generic Name J-Code Medicare Status Therapeutic Class Aubagio® Teriflunomide Medicare Part D Acthar® Corticotropin gel J0800 Medicare Part D Ampyra™ Dalfampridine Medicare Part D Arcalyst™ Rilonacept powder for solution J3490 Medicare Part D Berinert® Human C1 Inhibitor Medicare Part D Botulinum Toxin: Medicare Part D Botox® (P) Botulinum Toxins Type A Injections J0585 (type A) Dysport™ (N) Botulinum Toxins Type B Injections J0587 (type B) Myobloc® (N) Xeomin® (N) Cinryze® Human C1 Inhibitor Medicare Part B or D Dipeptidyl peptidase 4 (DPP- Medicare Part D IV) inhibitors: Tradjenta™ (P) Linagliptin Januvia™ (N) Sitagliptin Janumet™ (N) Sitagliptin and metformin Jentadueto™ (N) Linagliptin and metformin Junvisync™ (N) Sitagliptin and simvastatin Nesina™ (N) Alogliptin Onglyza™ (N) Saxagliptin Kazano™ (N) Alogliptin and metformin Kombiglyze™ XR (N) Saxagliptin and metformin ER Oseni™ (N) Alogliptin and pioglitazone Firazyr® (N) Icatibant Medicare Part D Gattex® (N) Teduglutide Medicare Part D Gilenya™ (N) Fingolimod Medicare Part D GLP-1 Receptor Agonists: Medicare Part D Bydureon™ (P) Exenatide Extended-Release Byetta™ (P) Exenatide SQ solution Victoza® (N) Liraglutide injection Growth Hormones: Somatropin (Growth hormone) injectable J2940-J2941 Medicare Part D Omnitrope® (P) Genotropin® (N) Humatrope® (N) Norditropin® (N) Nutropin AQ (N) Saizen® (N) Serostim® (N) Zorbtive® (N) Hyaluronic Acid Derivatives Hyaluronic Acid Injections J7321-J7322 Medicare Part B (viscosupplements):

Last Revised: March 10, 2014 Page 1 of 43 Brand Name and/or Generic Name J-Code Medicare Status Therapeutic Class Supartz® (P) Synvisc® (2) Euflexxa® (N) Hyalgan® (N) Orthovisc® (N) Synvisc-One® (N) Ilaris® Canakinumab Medicare Part D Imbruvica™ Ibrutinib Medicare Part D Invokana™ Canagliflozin Medicare Part D Juxtapid™ Lomitapide Medicare Part D Kalbitor® Ecallantide Medicare Part D Kalydeco™ Ivacaftor Medicare Part D Kuvan™ Sapropterin tablets J3490 Medicare Part D Kynamro™ Mipomersen sodium Medicare Part D Mozobil™ Plerixafor injection Medicare Part D Pomalyst® Pomalidomide Medicare Part D Procysbi™ Cysteamine delayed-release Medicare Part D Prolia® Denosumab Medicare Part D Provenge® Sipuleucel-T Q2043 Medicare Part B Ravicti® Glycerol phenylbutyrate Medicare Part D Sabril® Vigabatrin Medicare Part D Soliris® Eculizumab J1300 Medicare Part B Supprelin® LA Histrelin implant J9226 Medicare Part D Symlin® Pramlintide SQ solution J3490 Medicare Part D Tecfidera™ Dimethyl fumarate Medicare Part D Tysabri® Natalizumab IV solution J2323 Medicare Part B Xgeva® Denosumab Medicare Part B Xiaflex™ Collagenase clostridium histolyticum J0775 Medicare Part B injection Xolair® Omalizumab injectable J2357 Medicare Part D

P- Preferred 2-2nd line (if preferred failed) NP- Non-preferred

Last Revised: March 10, 2014 Page 2 of 43 Medications Requiring Review – Criteria for Use Drug Prior Authorization Criteria Aubagio® Candidates for treatment with Aubagio® should meet ALL the following criteria: (Teriflunomide) 1. Documented diagnosis of relapsing multiple sclerosis (MS) 2. Prescribed by a Neurologist 3. Documented inadequate response or unable to tolerate ONE interferon therapy (ie. Avonex®, Extavia® or Rebif®)* OR Copaxone®* 4. Documented disease progression on current MS therapy i. Patients who are stable and well-controlled (not having disease progressing symptoms) on other MS therapies should not be changed to Aubagio® 5. Females of child bearing age (12-50 years of age) should have a baseline negative pregnancy test (within 1 month) AND they must be on at least one form of effective contraception 6. Negative PPD (tuberculin) test 7. Used as monotherapy for treatment of relapsing MS

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

Due to the possibility of increased risk of infections: • Teriflunomide should be used as monotherapy and not in combination with Avonex® (interferon beta-1a), other beta-interferons (Betaseron® or Rebif®), or glatiramer acetate (Copaxone®). • Teriflunomide should usually not be used in patients who are receiving chronic immunosuppressant therapy, who are receiving other immunomodulatory drugs, or are significantly immunocompromised for any reason.

Reasons for non-coverage: Aubagio® should NOT be used in patients with any of the following: • Severe hepatic impairment • Pre-existing hepatic disease • Clinical conditions or on medications which could potentially affect or worsen hepatic function • Current leflunomide treatment • Pregnancy

Initial approval period: 6 months

Continued approval for treatment with Aubagio® should meet ALL the following criteria: 1. Review of compliance to Aubagio® 2. Documented beneficial effect from therapy 3. Documented ALT measured monthly for first six (6) months of therapy 4. Document serum transaminase, bilirubin, and CBC measured within (6) months of therapy

Continued approval: 1 year

Dosage and Administration • The recommended dose of Aubagio® is 7 mg or 14 mg daily.

Ordering information: Aubagio® is available through the KP Specialty Pharmacy. Prescribers must complete the KP-SP Aubagio Order Form and fax it to KP-Specialty Pharmacy (1-650-301-5790). 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) *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. Last Revised: March 1, 2014 Page 4 of 43 Drug Prior Authorization Criteria 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 exacerbations 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 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 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

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.

Notes: • Ampyra™ results were modest in published studies. o Only about 30% of clinical trial patients had an improvement in average walking speed of 20% or more (while about 10% of placebo-treated patients had the same level of improvement). To put this in perspective, an average 20% improvement in a timed walk over a 25-foot distance means on average the patient walked 25 feet 8 seconds if baseline was 10 seconds, or in 10 seconds if baseline was 12.5 seconds. o In clinical trials, a response was defined as having an improvement in walking speed in more than half of the timed 25-foot walk tests. In two trials, 35% and 43% of patients met this standard for improvement (versus 8% and 9% of placebo-treated patients. In *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. Last Revised: March 1, 2014 Page 6 of 43 Drug Prior Authorization Criteria the minority of patients who achieved this response criterion, the improvements amounted to just under 2 seconds improvement over 25 feet, versus a 0.5 second improvement with placebo. These average improvements should be weighed against the risks of treatment – primarily the risk for seizures.

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). 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)

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 Berinert® (Human Candidates for treatment with Berinert® should meet ALL the following criteria: 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

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

Non-preferred: Patients must meet ALL of the criteria for coverage: Dysport® Type A 1. Must be prescribed by a neurologist trained to inject botulinum toxin Injection 2. Chronic migraine headaches for > 6 months 3. Unsuccessful treatment with at least 3 classes of prophylactic medications with each agent at Myobloc® Type B the appropriate dose for 4-6 weeks. Examples of prophylactic medications include: Injections a. Beta Blockers i. Propranolol 20 mg to 240 mg by mouth daily in divided doses Xeomin® Type A ii. Atenolol 25 mg to 100 mg by mouth daily Injection iii. Timolol (NF) 20 mg to 20 mg by mouth daily in divided doses b. Antidepressants (TCA), SSRI, or SNRI) i. Nortriptyline 10 mg to 100 mg by mouth daily ii. Amitriptyline 10 mg to 100 mg by mouth daily iii. Venlafaxine 37.5 mg by mouth daily, titrate up to 150 mg daily c. Calcium Channel Blockers i. Verapamil SR 180 mg to 480 mg by mouth daily d. Anticonvulsants i. Divalproex DR: 500 to 1000 mg PO daily ii. Topiramate 100 to 200 mg PO daily in divided doses 4. Assessment and treatment of psychosomatic factors (e.g stress, depression, and anxiety) 5. Complete Neurological Evaluation 6. No contraindications (e.g. infection in target muscle, neuromuscular disorder, or sensitivity to Botox A)

Use of Botulinum Toxin for Hyperhidrosis*

Patient must meet ALL criteria for coverage: 1. Receive recommendation from Dermatology after failed medical treatment with Drysol® and Robinul®. 2. Medical complications from hyperhidrosis including skin maceration or dermatitis. 3. No history of neuromuscular disease. 4. No recent infection or malignancy in affected area.

Use of Botulinum Toxin for Blepharospasm**

Patient must meet ALL criteria for coverage 1. Diagnosis of bilateral blepharospasm 2. Jankovic Rating Scale (JRS) severity subscore > 2 3. No neuroleptic-induce blepharospasm 4. No known hypersensitivity to botulinum toxins, human serum albumin, or sucrose 5. 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) 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

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 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 Cinryze® Candidates for treatment with Cinryze® should meet ALL the following criteria: (Human C1

Reasons for non-coverage: • Treatment of angioedema acute attacks in adult and adolescent patients with HAE • Under 9 years of age

Monitoring: • Reduction in number, severity, and duration of swelling attacks • Symptoms of hypersensitivity during or after infusion • Signs of thrombosis

Short-term Prophylaxis: 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: 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, consider long-term prophylaxis. Options include:

Januvia™ DDP-IV inhibitors will be covered for current KP new start members who meet ALL of the following (Sitagliptin) criteria:

Onglyza™ 1. A diagnosis of type 2 diabetes mellitus (Saxagliptin) 2. Must be prescribed by an Endocrinologist 3. HgbA1c level 7%–9% Nesina™ 4. Failed to obtain adequate glycemic control on combination therapy with: (Alogliptin) 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 Non-Covered sulfonylurea therapy) and combination c. Maximum tolerated titration of insulin OR meets EITHER of the following criteria: products (separate i. The DPP-IV inhibitor may be initiated prior to insulin trial, in either of the prescriptions following two conditions: required for 1. Endocrinologist indicates hypoglycemia is uniquely undesirable, so ingredients in unable to use insulin (e.g., in patients who have hazardous jobs) OR combination 2. Endocrinologist indicates promotion of weight loss is a major products): consideration and this patients HgbA1c is close to target (<8.0%)

Kazano™ **As outlined above, DPP-IV inhibitors are not substitutes for insulin in patients whose diabetes control (Alogliptin and may benefit from insulin therapy. metformin) Reasons for non-coverage: Oseni™ (Alogliptin • Type 1 diabetes mellitus and pioglitazone) • Treatment of diabetic ketoacidosis • Concurrent use with insulin • Pediatric patients (<18 years old) Jentadueto™ • Prior history of a serious allergic reaction to DPP-IV inhibitors (i.e., anaphylaxis, angioedema, *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. Last Revised: March 1, 2014 Page 13 of 43 Drug Prior Authorization Criteria (Linagliptin and Stevens-Johnson syndrome, etc.) metformin) • Severe hepatic insufficiency (Child-Pugh score >9)

Kombiglyze™ XR Initial approval period: 6 months

(Saxagliptin and Continued approval: 1 year, based on review of compliance to therapy and documented improved metformin glycemic control as evidenced by HgbA1c lowering from pretreatment level to HgbA1c goal <8% extended-release) The preferred DPP-IV inhibitor, Tradjenta™, will be covered for new members to KP already taking Tradjenta ™ who meet the following criteria: Janumet™ 1. A diagnosis of type 2 diabetes mellitus and (Sitagliptin and 2. HgbA1c level <8% metformin) Non-preferred DPP-IV inhibitor will be covered for new members to KP already taking a non-preferred

DPP-IV inhibitor who meet the following criteria: Juvisync™ 1. A diagnosis of type 2 diabetes mellitus and (Sitagliptin and 2. HgbA1c level <8% and simvastatin) 3. Unable to tolerate or inadequate response to Tradjenta™.

***Note: New members to KP currently taking a DPP-IV inhibitor upon enrollment whose diabetes is not controlled with a DPP-IV inhibitor (i.e., HgbA1c> 8%) will need to meet the general criteria for KP new start members. Use caution in the following patients: • ESRD requiring hemodialysis or peritoneal dialysis • Pregnant/nursing women • Concomitant use with a sulfonylurea due to increased risk of hypoglycemia • History of pancreatitis

Monitoring: • Renal function prior to initiation of the DPP-IV inhibitor and periodically afterwards

• HgbA1c level • Serum glucose level • Development of pancreatitis after initiation or dose increases Firazyr® (Icatibant) Candidates for treatment with Firazyr® should meet ALL the following criteria:

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 (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

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/ 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:

Ordering information Gattex® is only available from certified pharmacies that are enrolled in the Gattex® REMS program. At this time, Gattex® is not available through our KP pharmacies or the KP Specialty Pharmacy. Prescriber’s should review the education materials which are part of the REMS and complete post-training knowledge assessment questions at http://www.gattexrems.com. Gilenya™ Candidates for treatment with Gilenya™ should meet ALL the following criteria: (Fingolimod) 1. Diagnosis of Multiple Sclerosis 2. Fingolimod (Gilenya™) should be reserved for treatment of relapsing forms of multiple sclerosis (MS). 3. Documented inadequate response or unable to tolerate ONE interferon therapy (ie. Avonex®, Extavia® or Rebif®)* OR Copaxone®* 4. Patient is having disease progressing symptoms on another MS therapy i. Patients who are stable and well-controlled (not having disease progressing symptoms) on other MS therapies should not be changed to fingolimod 5. Inadequate response to or unable to tolerate Aubagio® (unless contraindication to Aubagio® (see Aubagio® QRM criteria))

Due to the possibility of increased risk of infections: o Fingolimod should be used as monotherapy and not in combination with Avonex® (interferon beta-1a), other beta-interferons (Betaseron® or Rebif®), or glatiramer acetate (Copaxone®). o Fingolimod should usually not be used in patients who are receiving chronic immunosuppressant therapy, who are receiving other immunomodulatory drugs, or are significantly immunocompromised for any reason.

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

Initial approval period: 6 months

Continued approval: 1 year, based on review of compliance to therapy and documented beneficial effect from therapy with decrease in number of or no relapses and documentation of recent ophthalmologic examination (within 3-4 months)

Dosage and Administration • Fingolimod 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. • All patients should be observed for six hours after the first dose is given, monitoring for signs

Monitoring • All patients should be observed for six hours after the first dose is given, monitoring for signs and symptoms of bradycardia. o Patients at increased risk for bradycardia or bradyarrhythmia should have a baseline electrocardiogram (ECG) performed if an ECG has not been done in the previous 6 months. o Risk for development of bradycardia or heart block is considered to be increased in patient concurrently treated with beta blockers, calcium channel blockers, or antiarrhythmics (Class Ia or Class III) or in patients with “a low heart rate, history of syncope, sick sinus syndrome, 2nd degree or higher conduction block, ischemic heart disease, or congestive heart failure” according to Gilenya™ prescribing information. (Note: Class Ia antiarrhythmics include quinidine, procainamide, and disopyramide. Class III antiarrhythmics include amiodarone and sotalol.) • All Patients should have the following laboratory values completed within 6 months prior to initiating therapy: complete blood count (CBC), liver transaminase, and serum bilirubin o Patients should be monitored for any new signs or symptoms which might suggest PML. At the first such sign or symptom of PML, fingolimod treatment should be withheld immediately and diagnostic measures should be undertaken. • All Patients should have documented immunity to varicella zoster virus (chicken pox). • All patients should have a baseline ophthalmologic exam prior to initiation of fingolimod and at 3-4 months after treatment initiation. • For women of childbearing potential, patient agrees to use a form or contraception to prevent pregnancy during fingolimod treatment and for two months after discontinuation of fingolimod GLP-1 Receptor GLP-1 receptor agonists will be covered for current KP new start members who meet the following Agonists criteria: Preferred: 1. A diagnosis of type 2 diabetes mellitus and Bydureon™ 2. Must be prescribed by endocrinologist and (Exenatide 3. HgbA1c level 7%–9% and Extended-Release) 4. Failed to obtain adequate glycemic control on combination therapy with:

a. Maximum tolerated doses of metformin (unless patient is not a candidate for Byetta™ metformin therapy) and (Exenatide) b. Maximum tolerated doses of a sulfonylurea (unless the patient is not a candidate for a

sulfonylurea therapy) and Non-Preferred: c. Maximum tolerated titration of insulin. Victoza® i. GLP-1 receptor agonists may be initiated prior to insulin trial, in either of the (Liraglutide) following two conditions:

1. Endocrinologist indicates hypoglycemia is uniquely undesirable, so **NOTE**: unable to use insulin (e.g., in patients who have hazardous jobs) OR Non-preferred 2. Endocrinologist indicates promotion of weight loss is a major GLP-1 receptor consideration and this patients A1C is close to target (<8.0%) agonists are only to be used when a **As outlined above, GLP-1 receptor agonists are not substitutes for insulin in patients whose diabetes may benefit from insulin treatment** preferred GLP-1

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 to A1c goal <8%

Preferred GLP-1 receptor agonists will be covered for new members to KP already taking a preferred GLP-1 receptor who meet the following criteria: 1. A diagnosis of type 2 diabetes mellitus and 2. HgbA1c level <8%

Non-Preferred GLP-1 receptor agonists will be covered for new members to KP already taking a non- preferred GLP-1 receptor who meet the following criteria: 1. A diagnosis of type 2 diabetes mellitus and 2. HgbA1c level <8% and 3. Unable to tolerate or inadequate response to a preferred GLP-1 receptor agonists

***Note: New members to KP currently taking a preferred or non-preferred GLP-1 receptor agonist upon enrollment whose diabetes is not controlled (i.e., A1c> 8%) will need to meet the general criteria for KP new start members.

Use caution in the following patients: • Pregnant/nursing women (Pregnancy Category C) • Concomitant use with pharmacologic agents known to affect renal function/hydration status/ and or patients experiencing nausea/vomiting/diarrhea with or without dehydration (i.e., ace- inhibitors, NSAIDS, diuretics) • Concomitant use with a sulfonylurea (hypoglycemia) • Concomitant use with warfarin (increased INR, sometimes with bleeding) • Concomitant use with oral medications that require rapid gastric gastrointestinal absorption (GLP-1 receptor agonists slow gastric emptying) • Concomitant use with oral medications dependent on threshold concentrations for efficacy (i.e., contraceptives, antibiotics) – Patients should take drugs 1 hour prior to GLP-1 receptor agonist injection

Monitoring: • Renal function prior to initiation of a GLP-1 receptor agonist and periodically afterwards

**NOTE**: Non-preferred GLP-1 receptor agonists are only to be used when a preferred GLP-1 agonist (Bydureon™ or Byetta™) has failed 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 > 10 Serostim® 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 3. Children with Prader-Willi Syndrome confirmed by appropriate genetic testing WITHOUT **NOTE**: therapeutic contraindications: severe obesity or respiratory impairment; OR Non-preferred 4. Pre-pubertal children with chronic renal insufficiency, before renal transplant, providing: growth hormone is nutritional status optimized; metabolic abnormalities optimized; and steroid therapy only to be used minimized; OR when preferred 5. Patients who are small for gestational age and meet all the criteria below: (Omnitrope®) a. Patient is 2 years of age or older b. Child was born small for gestational age, defined as birth weight and/or length at least growth hormone two standard deviations below the mean for gestational age. has failed 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).

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

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

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; *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. Last Revised: March 1, 2014 Page 20 of 43 Drug Prior Authorization Criteria body composition, hip-to-waist ratio, cardiovascular health, bone mineral density, serum cholesterol, physical strength, or quality of life.

Continued Approval Period: 12 months 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 Rheumatology Preferred: 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) of Non-preferred: ONE of the following: acetaminophen (4 grams/day), NSAIDs, intraarticular corticosteroid nd Synvisc® (2 Line) injections, and other non-narcotic or narcotic analgesics 4. Efficacy of intra-articular corticosteroid injection lasting less than 6-8 weeks Euflexxa® (N) Hyalgan® (N) Initial Approval: 1 to 5 weeks depending on the product

Synvisc-One® (N) Criteria for Continuation of Therapy: There are no data on repeated courses of therapy for Euflexxa® and Supartz®; there is no evidence of inc **Note**: reased adverse drug events in repeated courses of therapy for Hyalgan®, Synvisc®, and Orthovisc® when Supartz® is the separated by at least six months. preferred medication. **Note: Supartz® is the preferred medication. Synvisc® may be approved if Supartz® is deemed Synvisc® may be 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) 1. Patient has documented 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). 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 either of the following: a. Prednisone b. Anakinra (Kineret®) injection

Reasons 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. Last Revised: March 1, 2014 Page 21 of 43 Drug Prior Authorization Criteria • Concurrent use of immunosuppressive therapy • Chronic, active, or recurrent infections • Untreated latent tuberculosis • Under 4 years of age

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) • Latent tuberculosis test prior to initiating therapy

Dosing: • 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. • 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.

Initial approval period: 1 month

Continued approval: Up to 1 year based on physician documentation of disease stability and improvement. Imbruvica™ Candidates for treatment with Imbruvica™ should meet the following criteria: (Ibrutinib) Criteria for mantle cell lymphoma: 1. Diagnosis of mantle cell lymphoma (MCL) 2. Prescribed by an oncologist 3. Documented inadequate response or unable to tolerate ONE of the following: a. R-CHOP [Rituxan, cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine), and prednisone] b. R-hyperCVAD [Rituxan, cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone alternating with high-dose cytarabine and methotrexate] c. FC-R or FC– fludarabine (Fludara) and cyclophosphamide with or without rituximab d. Velcade (bortezomib) e. Bendamustine (Treanda) with or without rituximab

Criteria for chronic lymphocytic leukemia: 1. Diagnosis of chronic lymphocytic leukemia (CLL) *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. Last Revised: March 1, 2014 Page 22 of 43 Drug Prior Authorization Criteria 2. Prescribed by an oncologist 3. Documented inadequate response or unable to tolerate ONE of the following: a. FC-R or FC– fludarabine (Fludara) and cyclophosphamide with or without rituximab b. Bendamustine (Treanda) with or without rituximab

Initial approval period: 6 months

Continued approval: 1 year, based on review of compliance to therapy, documented beneficial overall response rate from therapy and regular CBC monitoring

Dosage and Administration Capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules

Mantle cell lymphoma • The recommended dose of Imbruvica™ is 560 mg taken orally once daily (four 140 mg capsules once daily) Chronic lymphocytic leukemia • The recommended dose of Imbruvica™ is 420 mg taken orally once daily (three 140 mg capsules once daily)

Monitoring • Monitor complete blood counts monthly • Monitor for bleeding • Monitor patients for fever and infections and evaluate promptly • Periodically monitor creatinine levels and maintain hydration Invokana™ Invokana™ will be covered for current KP new start members who meet ALL of the following criteria: (Canagliflozin) 1. Documented diagnosis of type 2 diabetes mellitus 2. Prescribed by an Endocrinologist 3. HgbA1c level 7%–9% 4. 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 EITHER of the following criteria: i. The Invokana™ may be initiated prior to insulin trial, in either of the following two conditions: 1. Endocrinologist indicates hypoglycemia is uniquely undesirable, so unable to use insulin (e.g., in patients who have hazardous jobs) OR 2. Endocrinologist indicates promotion of weight loss is a major consideration and this patients HgbA1c is close to target (<8.0%)

**As outlined above, Invokana™ is not a substitute for insulin in patients whose diabetes control may benefit from insulin therapy

Invokana™ will be covered for new members to KP already taking Invokana™ who meet the following criteria: 1. A diagnosis of type 2 diabetes mellitus and 2. HgbA1c level <8%

Initial approval period: 6 months

Continued approval: 1 year, based on review of compliance to therapy and documented improved glycemic control as evidenced by HgbA1c lowering from pretreatment level to HgbA1c goal <8% 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: • 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_e ditable.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 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

Monitoring:

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 6 years or older 4. At least one copy of G551D mutation in the CF transmembrane conductance regulator (CFTR)

Reasons for non-coverage: Kalydeco™ will not be covered for members with one or more of the following criteria: • CF due to mutations other than G551D in the CFTR gene • Homozygous for the F508del mutation in the CFTR gene • Concomitant therapy with strong CYP3A4 inhibitors (e.g., rifampin, St. John’s wort).

Use caution in the following patients: • Patient with abnormal liver function defined as elevation in three or more of the following levels of >3 times the upper limit of normal: ALT, AST, AP, GGT or total bilirubin • Patient with CrCl <30 ml/min • Concomitant use of ivacaftor with strong CYP3A4 inducers (e.g., rifampin, St. John’s wort) substantially decreases available ivacaftor which may decrease effectiveness. Therefore, co- administration is not recommended.

Monitoring: • Monitor ALT/AST at baseline, every three months for one year, then once yearly thereafter

• Monitor efficacy via forced expiratory volume in on second (FEV1), patient weight and sweat chloride concentration (optional) • Monitor for adherence to drug regimen and for adverse events which could be related to treatment

Initial Approval: 6 months

Continued Approval: 12 months if patient has documented evidence of response to therapy and ALT/AST *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. Last Revised: March 1, 2014 Page 26 of 43 Drug Prior Authorization Criteria levels have been checked within the last 3 months.

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). 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: • 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™

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 Mozobil™ Candidates for Mozobil™ should meet ALL of the following criteria: (Plerixafor) injection 1. A diagnosis of non-Hodgkin’s lymphoma or multiple myeloma 2. Patient also prescribed a granulocyte-colony stimulating factor 3. Failed mobilization with standard doses of granulocyte-colony stimulating factor alone (Mozobil™ is not considered first-line therapy) 4. Must be 18 years of age or older

Mozobil™ will not be covered for members in the following categories: 1. Patients with leukemia 2. Pediatric patients

Approval Duration: Approved for up to 4 doses (1 dose per day) for up to 4 consecutive days

Dosing and Administration:

Monitoring: • Caution should be used in the following groups o Patient with moderate/severe renal impairment (CrCl<50mL/min) o Pregnant or nursing mothers • Monitor white blood cell counts during plerixafor use. Exercise clinical judgment when administering plerixafor to patients with peripheral blood neutrophil counts higher than 50,000/mcL • Monitor platelet counts in all patients who receive plerixafor and then undergo apheresis. • Monitor renal function • Peripheral blood CD 34+ cell count (cells/mcL) • Signs and symptoms of splenic enlargement (left upper abdominal pain and/or scapular or shoulder pain) and possible rupture Pomalyst® Candidates for treatment with Pomalyst® should meet ALL the following criteria: (Pomalidomide) 1. Documented diagnosis of multiple myeloma 2. Must be prescribed by an Oncologist who is a certified REMS provider *NOTE: For more information and to enroll, please go to the following site: [celgeneriskmanagement.com] 3. Documented inadequate response or unable to tolerate Revlimid® (lenalidomide) 4. Documented inadequate response or unable to tolerate Velcade® (bortezomib) 5. Demonstrated disease progression on or within 60 days of completion of the last therapy for multiple myeloma 6. If patient is a female of child bearing age (12-50 years of age), must have 2 baseline negative pregnancy test AND must be on at least one form of effective contraception

Reasons for non-coverage: • Pregnant women (Pregnancy Category X)

Initial Approval: 6 months

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

Dosage and Administration • 4 mg per day taken orally on days 1-21 of repeated 28-day cycles until disease progression

Monitoring: • Monitor patients for hematologic toxicities, especially neutropenia • Females of child bearing age (18-50 years of age), must have 2 baseline negative 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. Last Revised: March 1, 2014 Page 29 of 43 Drug Prior Authorization Criteria test. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing Pomalyst® and then weekly during the first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles

Ordering information: Pomalyst® is furnished by the KP Speicalty Pharmacy (KP SP) in Daly City, California. Fax the Pomalyst® Order Form to KP SP (650-301-5790). The Pomalyst® Order Form can be found on the KP SP Website. 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%

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

Initial Approval: 6 months (1 dose)

Continued Approval: 12 months (2 doses) if patient has documented clinical benefit from medication and no reported adverse events to Prolia®

Use Caution in the following patient population: • Renal impairment (CrCl of 30 ml/min or less) or end-stage renal disease requiring hemodialysis • Hypocalcemia

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

Monitoring: • Serum calcium prior to therapy initiation and periodically. Adequately supplement all patients with calcium and vitamin D • Symptoms of osteonecrosis of the jaw 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:

*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. Last Revised: March 1, 2014 Page 31 of 43 Drug Prior Authorization Criteria 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 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)

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 pretreatment 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. 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

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). 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 *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. Last Revised: March 1, 2014 Page 34 of 43 Drug Prior Authorization Criteria 75%

Monitoring: • Vision must be tested at baseline and every 3 months • 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.sabril. net&utm_content=/hcp/. Soliris® Candidates for Soliris® should meet ALL of the following criteria: (Eculizumab) 1. A documented diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) OR a diagnosis of atypical hemolytic uremic syndrome (must not be for the treatment of Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)) 2. Must be prescribed by a hematologist or oncologist 3. Must be > 18 years of age 4. Must be vaccinated with a quadravalent meningococcal vaccine at least 2 weeks before the first dose of eculizumab is administered (patients should be revaccinated according to medical guidelines or vaccine labeling)

Reasons for non-coverage: • Unresolved serious Neisseria meningitidis infection • Not currently vaccinated against Neisseria meningitidis infection.

Initial approval period: 1 year

Caution: • Use with caution in patients with systemic infections since eculizumab blocks complement, making patients more susceptible to infections • Administration may result in infusion reactions such as hypersensitivity or anaphylaxis

Monitoring: Paroxysmal nocturnal hemoglobinuria (PNH) • Patients should be monitored for infusion reactions. • Monitor patients for 8 weeks after discontinuation of Soliris® Atypical hemolytic uremic syndrome • Monitor patients for 12 weeks after discontinuation of Soliris®

Dosing: Paroxysmal nocturnal hemoglobinuria (PNH) • Weeks 1 through 4: 600 mg intravenously every 7 days • Week 5: 900 mg intravenously 7 days after the last dose • Week 6 through 52: 900 mg intravenously every 14 days • After the first year, eculizumab is dosed at 900 mg intravenously every 14 days Atypical hemolytic uremic syndrome • Weeks 1 through 4: 900 mg intravenously every 7 days • Week 5: 1200 mg intravenously 7 days after the last dose • Week 6 through 52: 1200 mg intravenously every 14 days • After the first year, eculizumab is dosed at 1200 mg intravenously every 14 days

Ordering information: Prescribers must be enrolled Soliris® REMS program. To enroll in the program, download and complete the Prescriber Introductory Letter and Enrollment Form at http://www.solirisrems.com/ and mail or fax it to Soliris OneSource Safety Support Program at 1-877-580-2596 (ALXN); or scan and e-mail it to [email protected]. 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

Monitoring: • LH, FSH, estradiol, or testosterone (after 1 month then every 6 months); height, bone age (every 6-12 months); tanner staging Symlin® Candidates for Symlin® should meet ALL of the following criteria: (Pramlintide) 1. Prescriber must be an Endocrinologist AND Type 1 diabetics 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™ Candidates for treatment with Tecfidera™ should meet ALL the following criteria: (Dimethyl 1. 18 years of age or older fumarate) 2. Documented diagnosis of relapsing multiple sclerosis (MS)

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

Initial approval period: 6 months

Continued approval: 1 year, based on review of compliance to therapy and documented beneficial effect from therapy

Tecfidera™ has not been studied as use as adjunct therapy in MS. Due to possibility of increased risk of infections should be considered as monotherapy.

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

Ordering information: Tecfidera™ is available through the KP specialty pharmacy. Prescribers must complete the KP Specialty Pharmacy form Tecfidera™ Prescription Order Form at http://pharmacy.kp.org/KP- CMS/California/DrugInformation/ViewMedSafetyDNMgmtCA.aspx?I32Object=1320&nodeValue=113 and fax it to KP-Specialty Pharmacy (1-650-301-5790). Tysabri® Candidates for Natalizumab (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: 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. Used for treatment of relapsing forms of multiple sclerosis (MS). 3. The potential benefits of natalizumab (Tysabri®) outweigh the risks from natalizumab therapy, including the risk of progressive multifocal leukoencephalopathy (PML) 4. Documented inadequate response or unable to tolerate to ONE interferon therapy (ie. Avonex®, Extavia® or Rebif®)* OR Copaxone®* 5. Patient failed therapy with Aubagio® (unless contraindication to Aubagio®(see Aubagio® QRM criteria)) 6. Patient is not stable or well-controlled (having disease progressing symptoms) on another MS therapy

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

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. Diagnosis of moderate to severe active Crohn’s disease 3. The potential benefits of natalizumab (Tysabri®) outweigh the risks from natalizumab therapy, including the risk of progressive multifocal leukoencephalopathy (PML) 4. Documented evidence of inflammation 5. Inadequate response or an inability to tolerate ONE conventional therapy (i.e sulfasalazine, mesalamine, azathioprine, or 6-mercaptopurine 6. Inadequate response or an inability to tolerate corticosteroids 7. Inadequate response or an inability to tolerate ONE TNF-α inhibitor (infliximab (Remicade), adalimumab (Humira), or Certolizumab (Cimzia)) 8. Tysabri not to be used concomitantly with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α

Multiple Sclerosis: Initial Approval: 3 months. Tysabri should be discontinued if clinical benefit has not been shown after 12 weeks. Continued approval: Reauthorization may be granted for up to one year with documented efficacy from the prescribing physician and compliance with the TOUCH program. Patients with a previous negative assay for anti-JCV antibodies must be retested annually to be considered for continued approval.

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

Continued approval: • 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. • For patients receiving therapeutic benefit and able to be tapered from 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. • Patients with a previous negative assay for anti-JCV antibodies must be retested annually to be considered for continued approval.

 Based upon evidence available at the time when these guidelines are being developed (03/2013): o Use in primary progressive MS is not supported by clinical trial evidence. o Efficacy or safety for use of natalizumab beyond two years is not supported by clinical trial evidence.  Due to the possibility of increased risk for PML or other infections: o Natalizumab should be used as monotherapy and not in combination with Avonex® (interferon beta-1a), other beta-interferons (Betaseron® or Rebif®), or glatiramer acetate (Copaxone®). *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. Last Revised: March 1, 2014 Page 39 of 43 Drug Prior Authorization Criteria o Natalizumab should usually not be used in patients who are receiving chronic immunosuppressant therapy, who are receiving other immunomodulatory drugs, or are significantly immunocompromised for any reason.

Dosage and Administration: Multiple sclerosis • Natalizumab 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. Natalizumab should NOT be given as a bolus or push. Crohn’s Disease • Natalizumab 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

Natalizumab should only be administered in an infusion center with adequate facilities for treating a hypersensitivity or infusion-related reaction.

Monitoring: • During the infusion and for at least one hour after completion of the infusion of natalizumab, patients should be observed for signs and symptoms of hypersensitivity or infusion-related reactions. o The natalizumab infusion must be stopped immediately, and the physician should be consulted immediately, if signs or symptoms related to a hypersensitivity reaction are seen. These may include urticaria, dizziness, fever, rash, rigors, pruritis, nausea, flushing, hypotension, dyspnea, or chest pain. • Patients should have a recent MRI brain scan prior to initiation of natalizumab treatment. This MRI may be helpful in differentiating MS symptoms from PML, should PML be suspected. o Patients should be monitored for any new signs or symptoms which might suggest PML. At the first such sign or symptom of PML, natalizumab treatment should be withheld immediately and diagnostic measures should be undertaken.

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. 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). Xgeva® Candidates for Xgeva™ should meet ALL of the following criteria: (Denosumab) 1. Diagnosis of bone metastases from solid tumors 2. A therapeutic trial and clinical failure with pamidronate OR zoledronic acid (Zometa®) a. Clinical failure defined as development of new skeletal related event (SRE) while receiving treatment with pamidronate or zolendronic acid for at least 3 months 3. Must be prescribed by an 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 *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. Last Revised: March 1, 2014 Page 40 of 43 Drug Prior Authorization Criteria

Reasons for non-coverage: • Treatment of skeletal-related events in patients with multiple myleoma • Renal impairment (CrCl of 30 ml/min or less) or end-stage renal disease requiring hemodialysis • 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 • Medication MUST be given by a health care professional

Monitoring: • Serum calcium prior to therapy initiation and periodically. Adequately supplement all patients with calcium and vitamin D • Symptoms of osteonecrosis of the jaw Xiflex™ Candidates for Xiaflex™ should meet ALL of the following criteria: (Collagenase Xiaflex™ is only available through the Xiaflex™ Experience Program Clostridium Histolticum) 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

Initial approval: 3 months

Dosage and Administration • 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

Use caution in the following patients: • Caution 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 Patients with Xolair® requests made by non-TSPMG pulmonary practitioners are required to be evaluated by a TSPMG pulmonary specialist prior to QRM approval for the medication.

1. Moderate to severe persistent asthma [based on criteria of the National Heart, Lung, and Blood Institute (NHLBIs) National Asthma Education and Prevention Program (NAEPP)] 2. Allergic asthma confirmed by positive skin testing or in vitro reactivity to a perennial aeroallergen? 3. Prescribed by a pulmonologist or allergy specialist 4. Baseline total IgE serum level from 30-700 int. units/mL 5. Currently using a high dose inhaled corticosteroid (or combination product) OR has a documented intolerance to inhaled corticosteroids

6. Currently on a long-acting β2 agonist (or combination product) OR has a documented

intolerance to long-acting β2 agonists? 7. Tried and failed or has a documented intolerance to a leukotriene modifier 8. Experiencing exacerbations of asthma symptoms requiring increased inhaled corticosteroid dosing, increased daily use of β2-agonist rescue medication or systemic steroids 9. 12 years of age or older

Exclusion Criteria: • History of adverse reaction to omalizumab or any of its • History of or high risk for cancer (See Adverse Events section of these Guidelines.) • Pregnancy (If patient becomes pregnant during therapy, omalizumab should be discontinued.) • Primary or secondary immunodeficiency and patients who are HIV-positive.

Initial Approval: 3 months

Continued Approval: 12 months, if the patient has experienced a reduction in the frequency of asthma exacerbations and has had reduction in the use of rescue medications or inhaled corticosteroids while treated with Xolair

Monitoring: • If omalizumab therapy is judged to be successful at four months, plan to continue treatment for up to one year. o Omalizumab therapy should be discontinued after one year. o Reevaluate asthma control at one, three, and six month intervals or as necessary. o If asthma control deteriorates during reevaluation, consider restarting omalizumab therapy. o Serum total IgE levels measured less than one year following discontinuation of omalizumab may not reflect steady state free IgE levels and should not be used to reassess the dosing regimen. Use serum IgE levels from pretreatment prior to initial dosing of omalizumab.