AHCCCS Pharmacy and Therapeutics Committee October 19 2016

AHCCCS Pharmacy and Therapeutics Committee October 19, 2016

August 16, 2016 Meeting Minutes • Review and Vote Reaching across Arizona to provide comprehensive quality health care for those in need 2

Magellan Class Reviews Classes o o o Antibiotics, Inhaled Cytokine and CAM Antagonists Epinephrine, Self-injected Growth Hormone Analgesics, Long-Acting Opioid Makena (hydroxyprogesterone) – Single Product Review New Products (to Magellan PDL classes) o Bevespi Aerosphere Reaching across Arizona to provide comprehensive quality health care for those in need 3

Antibiotics, Inhaled Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 4

Antibiotics, Inhaled Product Update: • Kitabis Pak is now available as a generic Guideline Update: • The Cystic Fibrosis Foundation guidelines for cystic fibrosis includes both nebulized tobramycin and aztreonam (Cayston) as recommended prophylaxis for Pseudomonas aeruginosa. Reaching across Arizona to provide comprehensive quality health care for those in need 5

Antibiotics, Inhaled The Cystic Fibrosis Foundation also recommends: • The alternate-month administration of both tobramycin and aztreonam in patients persistently infected with P. aeruginosa, although with a grade B recommendation (high certainty that net benefit is moderate or moderate certainty that net benefit is substantial. Reaching across Arizona to provide comprehensive quality health care for those in need 6

Antibiotics, Inhaled Preferred Products: • Kitabis Pak • Bethkis Reaching across Arizona to provide comprehensive quality health care for those in need 7

Cytokine and CAM Antagonists Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 8

Cytokine and CAM Antagonists New Products/Product Updates: • Taltz (ixekizumab) is indicated for the treatment of moderate to severe plaque psoriasis (reviewed in August) • Cosentyx is now indicated for the treatment of psoriatic arthritis and ankylosing spondylitis in adults (previously indicated only for plaque psoriasis) • Humira is now indicated for the treatment of noninfectious uveitis in adults Reaching across Arizona to provide comprehensive quality health care for those in need 9

Cytokine and CAM Antagonists New Products/Product Updates: • Xeljanz XR (tofacitinib) is now available as a once daily administration option (11 mg tablets). Label information is similar for that for Xeljanz. o Caution should be used in patients with preexisting gastrointestinal narrowing due to rare reports of obstructive symptoms in this population. o Should not be used when dose modifications are required Reaching across Arizona to provide comprehensive quality health care for those in need 10

Cytokine and CAM Antagonists Recent Studies: • The CLEAR study was a manufacturer-funded 52 -week comparison of Cosentyx and Stelara in patients with plaque psoriasis. Cosentyx treatment resulted in a statistically significant improvement in PASI 90 response compared to Stelara treatment at week 16. • FIXTURE studied Cosentyx vs. placebo and Enbrel in plaque psoriasis. Cosentyx was found to be superior to Enbrel as a secondary endpoint in this manufacturersponsored, active-control study. Reaching across Arizona to provide comprehensive quality health care for those in need 11

Cytokine and CAM Antagonists Guideline Update: • The American College of Rheumatology 2015 guidelines for treatment of rheumatoid arthritis recommend that non-TNF biologic is preferred in TNF inhibitor failure. o Xeljanz is generally recommended as an option following non-TNF biologic failure.

Cytokine and CAM Antagonists Guideline Update: The American College of Rheumatology released their first guideline on ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis. NSAIDs are recommended in patients with active AS. Those with active AS despite NSAID treatment should use a TNF blocker. No TNF blocker is listed as preferred over the others except in patients with concomitant irritable bowel disease or recurrent iritis, who should receive Remicade or Humira. Reaching across Arizona to provide comprehensive quality health care for those in need 13

Cytokine and CAM Antagonists Guideline Update: • The American Gastroenterology Association (AGA) has created a clinical algorithm: o Recommends an anti-TNF agent with or without a thiopurine; or vedolizumab (Entyvio) with or without thiopurine or methotrexate, for maintenance therapy in high-risk outpatients following induction therapy. o If induction therapy is done with either an anti. TNF agent or vedolizumab, these agents should be continued.

Cytokine and CAM Antagonists AGA Guideline Update continued: • In cases of loss of response to an anti-TNF agent, the anti-TNF dose should be optimized, and a switch within class, the addition of an immunomodulator, or a switch to vedolizumab may be considered. • In cases of loss of response to vedolizumab, the dose should be optimized, and a switch to an anti. TNF agent may be considered. • Infliximab may be used in inpatients who have failed IV steroids and for maintenance of remission.

Cytokine and CAM Antagonists Preferred Products: • Enbrel • Humira

Epinephrine, Selfinjected Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 17

Epinephrine, Self-injected Class Overview • No new clinical information to review Preferred Products • Epinephrine 0. 15 mg and 0. 3 mg (generic Adrenaclick) • Epipen Jr. Reaching across Arizona to provide comprehensive quality health care for those in need 18

Growth Hormone Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 19

Growth Hormone Product Updates • Nutropin AQ pen cartridges have been discontinued by Genentech. The Nu. Spin device will remain available. Preferred Products • Genotropin • Nutropin • Norditropin Reaching across Arizona to provide comprehensive quality health care for those in need 20

Analgesics, Long Acting Opioid Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 21

Analgesics, Long Acting Opioid Class Information • Products include: § Buprenorphine § Fentanyl • Hydromorphone • Methadone • Morphine • Oxycodone • Oxymorphone • Tapentadol • Tramadol across Arizona to provide comprehensive • quality health care for those in need 22

Analgesics, Long Acting Opioid Abuse -Deterrent Products • Morphine sulfate ER/naltrexone (Embeda) capsules; • Hydrocodone ER (Hysingla ER) tablets; • Oxycodone CR (Oxy. Contin) tablets; • Oxycodone ER (authorized generics for Oxy. Contin) tablets: and • Oxycodone ER (Xtampza ER) capsules. Reaching across Arizona to provide comprehensive quality health care for those in need 23

Analgesics, Long Acting Opioid Abuse -Deterrent Products continued • Hydromorphone ER (Exalgo)* • Oxymorphone ER (Opana ER)* • Tapentadol ER (Nucynta ER)* • Hydrocodone ER (Zohydro ER)* *Have abuse-deterrent properties but have not been approved by the FDA as abuse-deterrent Reaching across Arizona to provide comprehensive quality health care for those in need 24

Analgesics, Long Acting Opioid New Product: Belbuca (buprenorphine) • Indicated for the management of severe pain that requires around-the-clock, long-term opioid treatment. • Black box warning regarding addiction, abuse, and misuse; respiratory depression, accidental exposure; neonatal opioid withdrawal syndrome; and accidental exposure to children. • Contraindicated in patients with significant respiratory depression, severe bronchial asthma, and suspected gastrointestinal obstruction. Reaching across Arizona to provide comprehensive quality health care for those in need 25

Analgesics, Long Acting Opioid New Product: Belbuca (buprenorphine) • Warnings include use in elderly, cachectic, or debilitated patients or patients with chronic pulmonary disease; risk of prolonged QTc interval; severe hypotension; and risk of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness. Reaching across Arizona to provide comprehensive quality health care for those in need 26

Analgesics, Long Acting Opioid New Product: Belbuca (buprenorphine) • Belbuca is a CYP 3 A 4 substrate; it should be used with caution when initiating CYP 3 A 4 inhibitors or discontinuing CYP 3 A 4 inducers. • Caution should be exercised when concomitantly giving CNS depressants, benzodiazepines, or mixed agonist/antagonist or partial agonist opioids. • Common adverse effects include constipation, nausea, somnolence, vomiting, headache, and dizziness. Reaching across Arizona to provide comprehensive quality health care for those in need 27

Analgesics, Long Acting Opioid New Product: Belbuca (buprenorphine) • There are no data available in pregnant women to inform a drug-associated risk, but limited published data on the use of buprenorphine in pregnant women have not shown increased risk of major malformations. • Belbuca is applied once daily or every 12 hours, as tolerated. • Lower doses are recommended in severe hepatic impairment or in the presence of oral mucositis. • It is available in seven strengths ranging from 75 to 900 mcg buccal films. Reaching across Arizona to provide comprehensive quality health care for those in need 28

Analgesics, Long Acting Opioid New Product: Xtampza ER (oxycodone) • Indicated for the management of severe pain that requires around-the-clock, long-term opioid treatment. • Black box warning regarding addiction, abuse, and misuse; respiratory depression, accidental ingestion; neonatal opioid withdrawal syndrome; concomitant use with CYP 3 A 4 inhibitors; and accidental exposure to children. • Contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, and suspected gastrointestinal obstruction. Reaching across Arizona to provide comprehensive quality health care for those in need 29

Analgesics, Long Acting Opioid New Product: Xtampza ER (oxycodone) • Other warnings include use in elderly, cachectic, or debilitated patients or patients with chronic pulmonary disease; adrenal insufficiency; severe hypotension; and risk of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness. • Xtampza ER is a CYP 3 A 4 substrate. It should also be used with caution when used concurrently with CNS depressants, serotonergic drugs, and mixed agonist/antagonist or partial agonist opioids. Reaching across Arizona to provide comprehensive quality health care for those in need 30

Analgesics, Long Acting Opioid New Product: Xtampza ER (oxycodone) • Common adverse effects include nausea, headache, constipation, somnolence, and pruritus. • There are no data available in pregnant women to inform a drug-associated risk, but prolonged use can lead to neonatal opioid withdrawal syndrome. • Xtampza ER is given every 12 hours with food. The capsule contents can be sprinkled on food. Lower doses are recommended in severe hepatic impairment. Reaching across Arizona to provide comprehensive quality health care for those in need 31

Analgesics, Long Acting Opioid New Product: Xtampza ER (oxycodone) continued • It is available in five strengths ranging from 9 to 36 mg extended release capsules. • The abuse deterrent mechanism is the microsphere formulation (inactive ingredients) that makes the capsule contents difficult to manipulate for misuse and abuse. Reaching across Arizona to provide comprehensive quality health care for those in need 32

Analgesics, Long Acting Opioid Guideline/Regulatory Updates: • Centers for Disease Control and Prevention (CDC) released guidelines for prescribing opioids for chronic pain outside of active cancer, palliative, and end-of-life care • If opioids are deemed appropriate for a patient’s chronic pain, they recommend initial treatment with immediate-release opioids • Doses of ≥ 50 morphine milligram equivalents (MME)/day should prompt reassessment of the individual’s benefits and risks and use of ≥ 90 MME/day should be avoided Reaching across Arizona to provide comprehensive quality health care for those in need 33

Analgesics, Long Acting Opioid Guideline/Regulatory Updates continued: • A black boxed warning will be added to all opioidand benzodiazepine-containing product labels stating that concomitant use of opioids and benzodiazepines has resulted in serious adverse effects, including respiratory depression and death. Reaching across Arizona to provide comprehensive quality health care for those in need 34

Makena (hydroxyprogesterone) Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 35

Makena (hydroxyprogesterone) • Indication: To reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth • Women who have had a previous preterm birth are at increased risk for premature birth. • Preterm birth, defined as birth of an infant prior to 37 week of gestation, affects nearly 1 of every 9 infants born in the U. S. each year (CDC – July 2016) • There is a higher risk of serious disability or death the earlier the baby is born. Preterm-related causes of death accounted for 35% in 2008 of all infant deaths.

Makena (hydroxyprogesterone) • Dosing: Administer 250 mg (1 m. L) intramuscular (IM) every 7 days; Begin treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation; Continue administration once weekly until week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever occurs first • Available as multidose vial: 5 m. L (250 mg/m. L) and single-dose vial (preservative-free): 1 m. L (250 mg/m. L)

New Products (to Magellan PDL classes) Sarah Martinez, Pharm D Provider Synergies Reaching across Arizona to provide comprehensive quality health care for those in need 38

Bevespi Aerosphere (formoterol/glycopyrrolate) • Indicated for the long-term maintenance treatment of airflow obstruction in COPD patients • Black box warning regarding asthma-related death due to its LABA component as well as a notice that the product is not indicated for treatment of asthma • Contraindication with use of LABA without long -term controller medication for asthma despite the lack of asthma indication

Bevespi Aerosphere (formoterol/glycopyrrolate) • Other warnings include inappropriate use in acute symptom treatment, paradoxical bronchospasm, hypokalemia/hyperglycemia, worsening of urinary retention and/or narrowangle glaucoma, and use in patients with cardiovascular disorders, convulsive disorders, thyrotoxicosis, diabetes, and ketoacidosis • Use with caution when concurrently given with MAO inhibitors, tricyclic antidepressants, anticholinergics, xanthine derivatives, diuretics, or beta blockers

Bevespi Aerosphere (formoterol/glycopyrrolate) • Common adverse effects include urinary tract infection and cough • It is in pregnancy category C • Given as two inhalations twice daily • It is available as a 4. 8 mcg/9 mcg metered dose inhaler Reaching across Arizona to provide comprehensive quality health care for those in need 41

Oral Oncology Drugs Subcommittee Follow-up Suzi Berman Reaching across Arizona to provide comprehensive quality health care for those in need 42

HIV Subcommittee Follow-up Suzi Berman Reaching across Arizona to provide comprehensive quality health care for those in need 43

NEW DRUGS • Xiidra – Lifitegrast Ophthalmic Solutions • Zinbryta - Daclizumab • Ocaliva – Obeticholic Acid • Briviact - Brivaracetam Reaching across Arizona to provide comprehensive quality health care for those in need 44

Xiidra – Lifitegrast Ophthalmic Solutions • Indicated for dry eye disease • Dosage: 1 drop in eye(s) every 12 hours • Black Box Warning - None • Clinical Trials o Double-blinded Study o 1181 patients – 1067 received Xiidra placed into 4 groupings. o Majority of participants were female average of 59 years. Reaching across Arizona to provide comprehensive quality health care for those in need 45

Xiidra – Lifitegrast Ophthalmic Solutions • Clinical Trials Continued: Results were based on the: § Eye Dryness Score (EDS) q A score of 100 is maximal discomfort q Baseline EDS scores were: • 50 for Study Groups 1 & 2 • 70 for Study Groups 3 & 4 § Over the 12 week trials, the average reductions were: • 14. 5 points for Study Groups 1 & 2 • 36. 5 points for Study Groups 3 & 4 Reaching across Arizona to provide comprehensive quality health care for those in need 46

Xiidra – Lifitegrast Ophthalmic Solutions • Adverse reactions Irritation, dysgeusia (foul, salty, rancid, or metallic taste sensation in the mouth) and reduced visual acuity in 5 -25% of the patients o Blurred vision, conjunctival redness, eye irritation, headache, increased tearing, eye discharge, eye discomfort, eye pruritus and sinusitis in 1 -5% of the patients. o Reaching across Arizona to provide comprehensive quality health care for those in need 47

Xiidra – Lifitegrast Ophthalmic Solutions • Recommendation: Xiidra is the only FDA approved drug to treat the signs and symptoms of dry eye disease. The disease can be mild to severe and other products listed on the AHCCCS Drug List have been tried with success. o AHCCCS does not recommend adding Xiidra to the AHCCCS Drug List at this time. o Xiidra is available with prior authorization. o Reaching across Arizona to provide comprehensive quality health care for those in need 48

Zinbryta - Daclizumab • Indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (MS). • Due to its safety profile, Zinbryta should generally be reserved for patients who have had an inadequate response to two or more MS drugs. Reaching across Arizona to provide comprehensive quality health care for those in need 49

Zinbryta - Daclizumab • Dosage: 150 mg subcutaneously once monthly • Black Box Warnings: o Zinbryta can cause severe liver injury including life-threatening events including liver failure and autoimmune hepatitis. o Contraindicated for use in patients with preexisting hepatic disease or impairment. o Other Immune-Mediated Disorders Reaching across Arizona to provide comprehensive quality health care for those in need 50

Zinbryta - Daclizumab • Clinical Trial Result: Comparative trial of Zinbryta to Avonex for up to 144 weeks. o 1841 participants chosen by 1 or more relapses and 1 or more new brain lesions ( one of which had to occur in the 12 months prior to the trial) o The trial excludes patients with progressive forms of MS or scores of > 5 on the Expanded Disability Status Scale. o Clinical assessment were completed every 12 weeks and after relapse events. MRIs done at week. S 24 & 96. o Reaching across Arizona to provide comprehensive quality health care for those in need 51

Zinbryta - Daclizumab • Clinical Trials Results: • Zinbryta had a statistically significant effect on the annualized relapse rate and on the number of new or newly enlarging T 2 hyperintense lesions. • There was no statistically significant effect on 12 week confirmed disability progression • Statistically significant but is it clinically significant? Reaching across Arizona to provide comprehensive quality health care for those in need 52

Zinbryta - Daclizumab • Adverse Reactions in > 5% of the participants o Nasopharyngitis o Upper Respiratory Tract Infection o Rash o Influenza o Dermatitis o Oropharyngeal Pain & Bronchitis Reaching across Arizona to provide comprehensive quality health care for those in need 53

Zinbryta - Daclizumab • Recommendation is to not add Zinbryta to the AHCCCS Drug List because it is a third line agent. • Zinbryta is available through the prior authorization process. Reaching across Arizona to provide comprehensive quality health care for those in need 54

Ocaliva – Obeticholic Acid • Is approved for: o the treatment of primary biliary cholangitis (PBC); and o the treatment of Non-Alcoholic Fatty Liver Disease (NALFD) aka NASH, with fibrosis. o Used in combination with Ursodiol in adults with an inadequate response to Ursodiol, or as monotherapy in adults unable to tolerate Ursodiol. o Dosage: 5 mg once daily with a maximum dosage of 10 mg once daily. Reaching across Arizona to provide comprehensive quality health care for those in need 55

Ocaliva – Obeticholic Acid • Black Box Warning – None • Clinical Trials: o Randomized, double-blind, placebo-controlled, 12 -month trial – 216 participants o Participants were taking Ursodiol for at least 12 months and stable for least 3 months without Ursodiol because they did not tolerate it. o 93% of the patients received Ocaliva or Placebo + Ursodiol and 7% did not receive the Ursodiol. Reaching across Arizona to provide comprehensive quality health care for those in need 56

Ocaliva – Obeticholic Acid • Clinical Trial Results • Primary Endpoints: Reduction of Alkaline Phosphatase of at least 15%, n (%) o Normal bilirubin after 12 months of therapy. o • 46% of trial participants vs. 10% of placebo patients met the endpoint. Reaching across Arizona to provide comprehensive quality health care for those in need 57

Ocaliva – Obeticholic Acid • Adverse Reactions: o The most common adverse reactions for the 10 mg and titrating dose were: § Pruritus: 63% § Fatigue: 22% § Abdominal pain; 15% § Rash: 8. 5% § Oropharyngeal pain: 7. 5% § Dizziness: 7% § Constipation: 7% Reaching across Arizona to provide comprehensive quality health care for those in need 58

Ocaliva – Obeticholic Acid • Recommendation is to not add Ocaliva to the AHCCCS Drug List at this time. • Ocaliva will be reviewed internally at AHCCCS due to the prevalence of NAFLD and the $70 K annual cost of the drug. • In addition, we are expecting other agents to be approved in the near future for the treatment of NAFLD Reaching across Arizona to provide comprehensive quality health care for those in need 59

Briviact - Brivaracetam • Is indicated as adjunctive therapy for partialonset seizures for patients 16 years and older with epilepsy. • Dosage may be given up to 200 mg orally per day. • Black Box Warning – None • Clinical Trials - 3 fixed-dose, randomized, doubleblind, placebo-controlled, multicenter studies (Studies 1, 2, and 3), which included 1550 patients. Reaching across Arizona to provide comprehensive quality health care for those in need 60

Briviact - Brivaracetam • Clinical Trials continued: All trials had an 8 -week baseline period, during which patients were required to have at least 8 partial-onset seizures. o The primary efficacy outcome in Study 1 and Study 2 was the percent reduction in 7 -day partial-onset seizure frequency over placebo. o The primary outcome for Study 3 was the percent reduction in 28 -day partial-onset seizure frequency over placebo. o Reaching across Arizona to provide comprehensive quality health care for those in need 61

Briviact - Brivaracetam • Clinical Trial Results: Percent reduction in partialonset seizure frequency over placebo: 7 -day Study § 50 mg/day dose = 8. 5% (n=99) § 100 mg/day dose = 17% (n=100) o 7 -day Titration Dose Study § 50 mg/day titrated dose = 16. 9% (n=101) o 28 -day Study § 100 mg/day dose = 25. 2% (n=252) § 200 mg/day dose = 25. 7% (n=249) o Reaching across Arizona to provide comprehensive quality health care for those in need 62

Briviact - Brivaracetam • Adverse Reactions occurring in > 10% of study participants: o Abnormal Gail, Ataxia, Dizziness, Drowsiness o Equilibrium Disturbances, Fatigue, Hypersomnia, Lethargy, Malaise, Psychiatric Disturbances, Sedation, Vertigo o Neuromuscular and Skeletal Weakness o Nystagmus Reaching across Arizona to provide comprehensive quality health care for those in need 63

Briviact - Brivaracetam • Recommendation is to not add this to the AHCCCS Drug List because there are several medications listed on the AHCCCS Drug List for use as augmentation strategies for epilepsy. • Briviact is available through the prior authorization process. Reaching across Arizona to provide comprehensive quality health care for those in need 64

Opioid 7 -day Quantity Limitation Shana Malone, AHCCCS Reaching across Arizona to provide comprehensive quality health care for those in need 65

Pill Splitting Steve Chakmakian, CMO United Community Plan Reaching across Arizona to provide comprehensive quality health care for those in need 66

Agenda Items for the January 25, 2017 P&T Meeting • Inhaled Glucocorticoid Drug Class • Generic Drug Pricing Reaching across Arizona to provide comprehensive quality health care for those in need 67

Thank You. Reaching across Arizona to provide comprehensive quality health care for those in need 68