AHCCCS Pharmacy and Therapeutics Committee 16 October 2019

AHCCCS Pharmacy and Therapeutics Committee 16 October 2019

AHCCCS Pharmacy and Therapeutics Committee 16 October 2019 Welcome and Introductions Sara Salek, MD, Chief Medical Officer, AHCCCS o Meeting Minutes 23 May 2019 o Review o Vote Reaching across Arizona to provide comprehensive quality health care for those in need 2 Conflict of Interest Training Robert L. Ellman

Reaching across Arizona to provide comprehensive quality health care for those in need 3 Magellan Class Reviews Classes for Review: Non-Supplemental Rebate Class Review Antifungals, Oral Antifungals, Topical Antimigraine Agents, Triptans Beta Blockers BPH Treatments Reaching across Arizona to provide comprehensive quality health care for those in need 4

Magellan Class Reviews Classes for Review: Non-Supplemental Rebate Class Review Calcium Channel Blockers Leukotriene Modifiers Phosphate Binders Sedative Hypnotics Topical Steroids Low, Medium, High & Very High Potency Reaching across Arizona to provide comprehensive quality health care for those in need 5 Magellan Drug Class Reviews Hind Douiki, Pharm.D.

Reaching across Arizona to provide comprehensive quality health care for those in need 6 Antifungals, Oral Reaching across Arizona to provide comprehensive quality health care for those in need 7 Antifungals, Oral Class Overview - Product indications include*: Candidiasis (esophageal, oropharyngeal, and vaginal) Cryptococcal infections Tinea topical infections Onychomycosis

Invasive aspergillosis *Not inclusive of all product indications, all products differ in indication Reaching across Arizona to provide comprehensive quality health care for those in need 8 Antifungals, Oral Class Overview:

clotrimazole troche - (clotrimazole troche) fluconazole - (Diflucan, fluconazole) flucytosine - (Ancobon, flucytosine) griseofulvin suspension - (griseofulvin suspension) griseofulvin microsized - (griseofulvin microsized) griseofulvin ultramicrosized - (griseofulvin ultramicrosized) isavuconazonium - (Cresmba) itraconazole - (itraconazole, Onmel, Sporanox) itraconazole (Tolsura) Reaching across Arizona to provide comprehensive quality health care for those in need 9 Antifungals, Oral Class Overview

ketoconazole - (ketoconazole) miconazole - (Oravig) nystatin - (nystatin) posaconazole - (Noxafil) terbinafine - (terbinafine) voriconazole - (Vfend, voriconazole) Reaching across Arizona to provide comprehensive quality health care for those in need 10 Antifungals, Oral Antifungal agents have different spectrums of activity and are FDA-approved to treat a variety of infections

Oral antifungal agents are useful in the treatment of a variety of infections in both immunocompetent and immunocompromised patients Few trials have been performed to compare safety and efficacy profiles of the drugs Many of the agents carry boxed warnings related to adverse events and/or drug interactions Reaching across Arizona to provide comprehensive quality health care for those in need 11 Antifungals, Oral

Due to its excellent penetration into many tissues, fluconazole is an effective Candida treatment for a variety of infections, lacking concerns about pH-dependent absorption such as that seen with ketoconazole Effective therapy for oropharyngeal candidiasis includes fluconazole, itraconazole, ketoconazole, nystatin, and clotrimazole Voriconazole has been shown to have similar efficacy to fluconazole in the treatment of esophageal candidiasis; however, more adverse effects are reported with voriconazole Posaconazole oral suspension has an indication for treatment of Reaching across when Arizona to provide comprehensive oropharyngeal candidiasis refractory to itraconazole

12 quality health care for those in need and/or fluconazole Antifungals, Oral Nystatin is also used to treat intestinal candidiasis and may be used in infants and children Isavuconazonium, posaconazole, flucytosine, voriconazole, itraconazole, and fluconazole have indications for the treatment and/or prophylaxis of various serious fungal infections Reaching across Arizona to provide comprehensive quality health care for those in need 13 Antifungals, Oral

Product Updates: Vfend is now indicated to include patients as young as 2 years of age for the treatment of invasive aspergillosis, candidemia, esophageal candidiasis, and serious fungal infections caused by select organisms in patients intolerant of or refractory to other therapy Dosing in this population is weight-based and dependent on the indication Reaching across Arizona to provide comprehensive quality health care for those in need 14 Antifungals, Topical Reaching across Arizona to provide comprehensive quality health care for those in need

15 Antifungals, Topical Class Overview - Product indications include*: Cutaneous Candidiasis Tinea Pedis Tinea Corporis Tinea Cruris Tenia Versicolor Topical Onychomycosis Seborrheic Dermatitis *Not inclusive of all product indications, all products differ in indication Reaching across Arizona to provide comprehensive quality health care for those in need 16 Antifungals, Topical Class Overview

butenafine - (Mentax) butenafine - (butenafine [OTC], Lotrimin Ultra [OTC]) ciclopirox 0.77% - (Ciclodan Cream, Kit; ciclopirox cream; Loprox Cream, Gel, Suspension) ciclopirox 8% - (Ciclodan Solution, ciclopirox 8%, Penlac) clotrimazole - (Alevazol [OTC], clotrimazole [OTC], Lotrimin AF [OTC]) clotrimazole/betamethasone - (clotrimazole/betamethasone, DermacinRx Therazole Pak, Lotrisone) econazole cream - (econazole) econazole foam - (Ecoza) Reaching across Arizona to provide comprehensive quality health care for those in need 17 Antifungals, Topical Class Overview: efinaconazole - (Jublia)

ketoconazole - (Extina, ketoconazole, Nizoral A-D Shampoo, Nizoral Shampoo, Xolegel) luliconazole - (Luzu) miconazole - (Azolen [OTC], Desenex [OTC] , Fungoid [OTC], Lotrimin AF Spray, [OTC], miconazole [OTC], Zeasorb [OTC]) miconazole/zinc oxide/white petrolatum - (Vusion) naftifine - (naftifine, Naftin) nystatin - (nystatin) nystatin/triamcinolone - (nystatin/triamcinolone) Reaching across Arizona to provide comprehensive quality health care for those in need 18 Antifungals, Topical Class Overview oxiconazole - (oxiconazole, Oxistat) sertaconazole - (Ertazco) sulconazole - (Exelderm)

tavaborole - (Kerydin) terbinafine - (Lamisil [OTC], Lamisil AT [OTC], terbinafine [OTC]) tolnaftate - (Fungoid-D [OTC], Lamisil AF Defense [OTC], Tinactin [OTC], tolnaftate [OTC]) undecylenic acid - (Hongo Cura, Sponix Anti-Fungal [OTC]) undecylenic acid/zinc undecylenic - (Fungi-Nail [OTC], Hongo Cura [OTC]) Reaching across Arizona to provide comprehensive quality health care for those in need 19 Antifungals, Topical

Topical antifungal agents have different spectrums of activity and are FDA-approved to treat a variety of infections Topical agents may be formulated as creams, foams, gels, lacquers, lotions, ointments, powders, solutions and sprays Many topical antifungal preparations are available as prescription medications and over-the-counter (OTC) products Limited data are available regarding comparative efficacy in the treatment of the various fungal infections tinea cruris, tinea corporis, tinea pedis, and tinea versicolor Combination therapy (antifungal plus corticosteroid) can be considered when inflammation is present Reaching across Arizona to provide comprehensive quality health care for those in need 20 Antifungals, Topical Data are also lacking in comparative

efficacy for the treatment of seborrheic dermatitis Based on limited efficacy data, choice of therapy is mainly based on clinical judgment with regard to prior treatments and complicating conditions, such as bacterial growth or intense inflammation Reaching across Arizona to provide comprehensive quality health care for those in need 21 Antifungals, Topical Product Updates: None Reaching across Arizona to provide comprehensive quality health care for those in need

22 Antimigraine Agents, Triptans Reaching across Arizona to provide comprehensive quality health care for those in need 23 Antimigraine Agents, Triptans Class Overview: almotriptan malate - (almotriptan) eletriptan - (eletriptan & (AG); Relpax) frovatriptan - (frovatriptan; Frova) naratriptan - (Amerge; naratriptan) rizatriptan - (Maxalt, Maxalt MLT; rizatriptan ODT & tablet) sumatriptan - (Imitrex Kit, Tablet & Vial; Imitrex Nasal; sumatriptan kit, nasal, tablet & vial; Onzetra Xsail; Sumavel DosePro; Zembrace SymTouch)

Reaching across Arizona to provide comprehensive quality health care for those in need 24 Antimigraine Agents, Triptans Class Overview: sumatriptan/naproxen (sumatriptan/naproxen; Treximet) sumatriptan camphor/menthol - (Migranow) zolmitriptan - (zolmitriptan ODT, ODT (AG), tablets, tablets (AG); Zomig, ZMT) Reaching across Arizona to provide comprehensive quality health care for those in need 25 Antimigraine Agents, Triptans

Migraines account for 10% to 20% of all headaches in adults and affect over 39 million men, women, and children in the United States Migraine headaches must be differentiated from regular tensiontype headaches. Key criteria for migraine diagnosis include an episodic headache lasting from 4 to 72 hours with at least two of the following: unilateral pain, throbbing, aggravation of pain upon moving, pain of moderate to severe intensity accompanied by nausea, vomiting, photophobia, or phonophobia Non-opioid analgesia with acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), or caffeinated combinations are Reaching across Arizona to provide comprehensive quality health

for those into need moderate migraine pain considered first-line therapy forcaremild 26 Antimigraine Agents, Triptans Migraine-specific agents (triptans, dihydroergotamine [DHE]) should be used in patients who experience moderate to severe migraine attacks Due to well-established efficacy, triptans have become the drugs of choice for treating acute migraine attacks The US Headache Consortium, a multidisciplinary panel of several professional organizations, recognized that all of the triptans are effective agents for the acute treatment of migraine

Data reviewed did not demonstrate that any specific triptan was superior to others and triptans appear to be equally safe Reaching across Arizona to provide comprehensive quality health care for those in need 27 Antimigraine Agents, Triptans Per the American Academy of Neurology (AAN) and the American Headache Society (AHS), for pharmacologic treatment for episodic migraine prevention in adults: o Antiepileptic drugs (divalproex sodium, sodium valproate, topiramate) and beta-blockers (metoprolol, propranolol, timolol) are considered effective in migraine prevention o Frovatriptan is established for short-term menstruallyassociated migraine (MAM) prevention o Naratriptan, zolmitriptan, antidepressants (amitriptyline,

venlafaxine), and beta-blockers (atenolol, nadolol) are considered probably effective in migraine prevention Reaching across Arizona to provide comprehensive quality health care for those in need 28 Antimigraine Agents, Triptans In addition to approval in adults, almotriptan, sumatriptan/naproxen, and zolmitriptan nasal spray are FDA-approved for use in patients 12 to 17 years old while rizatriptan is approved in patients 6 to 17 years old Non-oral routes of administration are available when nausea or vomiting present as significant components of migraine attacks Reaching across Arizona to provide comprehensive quality health care for those in need

29 Antimigraine Agents, Triptans Product Updates: Tosymra (sumatriptan nasal spray) is indicated for the acute treatment of migraine with or without aura in adults It is approved as a single 10 mg spray to be administered in one nostril and may be repeated up to a maximum of 30 mg in 24 hours with at least one hour separating doses Tosymra may also be given with at least one hour between other sumatriptan products Contraindications, warnings, drug interactions, and adverse reactions are similar to other sumatriptan products Endo announced discontinuation of Sumatriptan injection with needle-free delivery system (Sumavel DosePro) 4 mg/0.5 mL (in 2016) and 6 mg/0.5 mL (in February 2018) due to business reasons Reaching across Arizona to provide comprehensive quality health care for those in need

30 Antimigraine Agents, Triptans Product Updates: The AAN and the AHS issued new guidelines on pharmacologic treatment for pediatric migraine prevention as an update to the AAN's 2004 guidelines. Key recommendations include: o Counsel patients/caregivers on lifestyle modifications o Advise patients and caregivers that most trials of preventive medications have failed to show any benefit over placebo in children, except propranolol which may "possibly result in a 50% reduction in headache frequency o Counsel patients/caregivers to treat an attack early for most Reaching across Arizona

to providesolution comprehensive benefit (first-line ibuprofen oral [10 mg/kg] in children 31 quality health care for those in need and adolescents) Antimigraine Agents, Triptans Product Updates: Sumatriptan/naproxen tablets and zolmitriptan nasal spray are options in adolescents Offer antiemetics to treat substantial nausea and vomiting Counsel patients/caregivers about medication overuse Reaching across Arizona to provide comprehensive

quality health care for those in need 32 Beta Blockers Reaching across Arizona to provide comprehensive quality health care for those in need 33 Beta Blockers Class Overview - Product indications include*: Hypertension Heart Failure Angina pectoris Myocardial Infarction Cardiac Arrhythmias Migraine Prophylaxis

Tremor Hypertrophic subaortic stenosis *Not inclusive of all product indications, all products differ in indication Reaching across Arizona to provide comprehensive quality health care for those in need 34 Beta Blockers Class Overview: Single Agents acebutolol - (acebutolol, Sectral) atenolol - (atenolol, Tenormin) betaxolol - (betaxolol) bisoprolol - (bisoprolol) carvedilol - (carvedilol, Coreg) carvedilol extended-release - (carvedilol ER, Coreg CR) labetalol - (labetalol) metoprolol succinate ER - (metoprolol succinate ER, Toprol XL, Kapspargo Sprinkle)

metoprolol tartrate - (Lopressor, metoprolol tartrate) Reaching across Arizona to provide comprehensive quality health care for those in need 35 Beta Blockers Class Overview: Single Agents nadolol - (Corgard, nadolol) nebivolol - (Bystolic) pindolol - (pindolol) propranolol - (propranolol) propranolol - (Hemangeol) propranolol ER - (Inderal XL, Innopran XL) propranolol LA - (Inderal LA, propranolol LA) sotalol - (Betapace, sotalol) Reaching across Arizona to provide comprehensive quality health care for those in need

36 Beta Blockers Class Overview: Single Agents sotalol - (Betapace AF, sotalol AF) sotalol - (Sotylize) timolol - (timolol) Class Overview: Beta-Blocker/Diuretic Combinations

atenolol/chlorthalidone - (atenolol/chlorthalidone, Tenoretic) bisoprolol/HCTZ - (bisoprolol/HCTZ , Ziac) metoprolol succinate/HCTZ - (Dutoprol, metoprolol succinate/HCTZ) metoprolol tartrate/HCTZ - (metoprolol tartrate/HCTZ) Reaching across Arizona to provide comprehensive quality health care for those in need 37 Beta Blockers Class Overview: Beta-Blocker/Diuretic Combinations nadolol/bendroflumethiazide - (Corzide, nadolol/bendroflumethiazide) propranolol/HCTZ - (propranolol/HCTZ) Reaching across Arizona to provide comprehensive quality health care for those in need

38 Beta Blockers Approximately 75 million (32%) of adults in the United States have hypertension Highest prevalence is among African American men and women at 43% and 45.7%, respectively It is estimated that hypertension is controlled in only 54% of patients with the condition Hypertension is an independent risk factor for the development of cardiovascular disease (CVD) Beta-blockers are one of the classes suggested as first-line therapy in patients with coronary artery disease (CAD), post-MI, HF, and

diabetes Reaching across Arizona to provide comprehensive quality health care for those in need 39 Beta Blockers Beta-blockers have similar efficacy for the treatment of hypertension (HTN) The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8) does not recommend beta-blockers as initial treatment of

hypertension This is due to a demonstrated higher rate of the primary composite outcome of CV death, MI, or stroke compared to use of an ARB with beta blocker use, a finding that was driven largely by an increase in stroke Beta-blockers prevent recurrent ischemia, life-threatening Reaching across Arizona to provide comprehensive ventricular arrhythmias, reduce the incidence of sudden cardiac 40 quality health care for those in need Beta Blockers The 2007 ACC/AHA chronic stable angina guidelines recommend indefinite beta-blocker therapy for blood pressure control in patients with CAD, acute coronary

syndrome (ACS), or left ventricular dysfunction (LVD), with or without heart failure symptoms Beta-blockers have also been shown to reduce mortality in patients with chronic heart failure (bisoprolol, carvedilol, and metoprolol succinate extended-release) Reaching across Arizona to provide comprehensive quality health care for those in need 41 Beta Blockers Product Updates: The American Academy of Pediatrics published a guideline on the management of infantile hemangiomas For infants with potentially problematic hemangiomas, early intervention and/or referral is recommended When systemic treatment is indicated, propranolol is the drug of choice as 2 to 3 mg/kg/day for at least 6 months and

is often continued until the patient is 12 months of age Select cases may be treated with topical timolol Reaching across Arizona to provide comprehensive quality health care for those in need 42 BPH Treatments Reaching across Arizona to provide comprehensive quality health care for those in need 43 BPH Treatments Class Overview: Alpha-Blockers alfuzosin ER - (alfuzosin ER, Uroxatral) doxazosin - (Cardura, doxazosin) doxazosin ER - (Cardura XL)

silodosin - (Rapaflo, silodosin) tamsulosin - (Flomax, tamsulosin) terazosin - (terazosin) Reaching across Arizona to provide comprehensive quality health care for those in need 44 BPH Treatments Class Overview: 5-Alpha Reductase (5AR) Inhibitors dutasteride - (Avodart, dutasteride) finasteride - (finasteride, Proscar) Class Overview: 5-Alpha Reductase (5AR) Inhibitor/Alpha Blocker Combinations dutasteride/tamsulosin - (dutasteride/tamsulosin, Jalyn) Class Overview: Phosphodiesterase 5 (PDE5) Inhibitors tadalafil - (Cialis, tadalafil)

Reaching across Arizona to provide comprehensive quality health care for those in need 45 BPH Treatments Benign prostatic hyperplasia (BPH) is one of the most common conditions in aging men As many as 14 million men in the United States have symptoms related to BPH An estimated 50% of men demonstrate histopathologic BPH by age 60

years; this etiology increases to 90% by 85 years of age Drugs used in the treatment of BPH relieve lower urinary tract symptoms (LUTS) and prevent complications and, in some cases, are an alternative to surgical intervention All products are indicated for the treatment of symptomatic BPH but none are indicated for prevention of prostate cancer Various products carry other non-BPH indications Reaching across Arizona to provide comprehensive quality health care for those in need 46 BPH Treatments

The American Urological Association (AUA) 2010 standards were reaffirmed in 2014 They state patients with mild symptoms of BPH (AUA Symptom Score < 8) and patients with moderate or severe disease (AUA Symptom Score > 8) who are not bothered by their symptoms generally do not require pharmacologic intervention Alpha-adrenergic blocker therapy is an appropriate treatment option for patients with moderate to severe LUTS secondary to BPH The AUA indicates that alfuzosin, doxazosin, tamsulosin, and terazosin have equal clinical effectiveness However, selective alpha-blockers such as alfuzosin, tamsulosin, and silodosin may have a decreased incidence of hypotension-related Reaching across Arizona to provide comprehensive adverse events quality health care for those in need 47

BPH Treatments Silodosin did not have published peer-reviewed studies prior to the guideline update Guidelines state the 5AR inhibitors are appropriate and effective treatments for patients with LUTS associated with demonstrable prostatic enlargement, but not for men with LUTS who do not have evidence of prostatic enlargement 5AR inhibitors may be used to prevent progression of LUTS secondary to BPH and to reduce the risk of urinary retention and future prostaterelated surgery Combination therapy utilizing an alpha blocker and a 5-reductase inhibitor is an appropriate and effective treatment for patients at highest risk for disease progression and for those who exhibit LUTS

symptoms and have definitive prostatic enlargement Reaching across Arizona to provide comprehensive quality health care for those in need 48 BPH Treatments The NIH-funded Medical Therapy of Prostatic Symptoms (MTOPS) and CombaT studies indicated that combination therapy is likely to be more effective at inhibiting disease progression than monotherapy 5ARs are not to be administered to women or children. Women who are pregnant or who may become pregnant should not handle dutasteride capsules or finasteride tablets Reaching across Arizona to provide comprehensive

quality health care for those in need 49 BPH Treatments Product Updates: None Reaching across Arizona to provide comprehensive quality health care for those in need 50 Calcium Channel Blockers Reaching across Arizona to provide comprehensive quality health care for those in need

51 Calcium Channel Blockers Class Overview - Product indications include*: Hypertension Angina Vasospastic Angina Ventricular Rate Control Unstable Angina Coronary Artery Disease Subarachnoid hemorrhage *Not inclusive of all product indications, all products differ in indication Reaching across Arizona to provide comprehensive quality health care for those in need 52 Calcium Channel Blockers Class Overview: Dihydropyridines

amlodipine - (amlodipine, Norvasc) felodipine ER - (felodipine ER, Plendil) isradipine - (isradipine) nicardipine - (Cardene, nicardipine) nicardipine SR - (Cardene SR) nifedipine - (nifedipine, Procardia) nifedipine ER, SA, SR - (Adalat CC; Afeditab CR; Nifediac CC; Nifedical XL; nifedipine ER, SA, SR; Procardia XL) nimodipine - (nimodipine) Reaching across Arizona to provide comprehensive quality health care for those in need 53 Calcium Channel Blockers Class Overview: Dihydropyridines nimodipine solution - (Nymalize) nisoldipine ER- (nisoldipine ER, Sular) Class Overview: Non-dihydropyridines

diltiazem - (Cardizem, diltiazem) diltiazem ER - (Cardizem LA, diltiazem ER, Matzim LA) diltiazem ER - (Cardizem CD; Cartia XT; diltiazem ER; Dilacor XR; Dilt CD; Taztia XT; Tiazac) Reaching across Arizona to provide comprehensive quality health care for those in need 54 Calcium Channel Blockers Class Overview: Non-dihydropyridines diltiazem ER - (Dilt XR, Diltia XT) verapamil - (Calan, verapamil) verapamil ER - (Covera-HS) verapamil ER - (verapamil ER, Verelan PM) verapamil SR - (Calan SR, Isoptin SR, verapamil ER, Verelan)

Reaching across Arizona to provide comprehensive quality health care for those in need 55 Calcium Channel Blockers Calcium channel blockers (CCBs) are widely used in the treatment of hypertension and angina pectoris Per the JNC-8, first-line therapy for HTN in the non-African American population is a thiazide-type diuretic, a CCB, an ACE inhibitor, or an angiotensin receptor blocker (ARB)

They recommend a thiazide diuretic or CCB for African Americans The benefits of CCBs in controlling angina and hypertension have been clearly documented No CCB has demonstrated a clinical advantage over other CCBs in the treatment of hypertension Dihydropyridine CCBs may cause a baroreceptor-mediated reflex increase in heart rate because of their potent peripheral vasodilating effects Reaching across Arizona to provide comprehensive quality health care for those in need

56 Calcium Channel Blockers Diltiazem decreases atrioventricular conduction and heart rate Verapamil decreases heart rate, slows atrioventricular nodal conduction to the greatest extent of the CCBs, and is useful for supraventricular tachyarrhythmias Short-acting nifedipine has been related to increased coronary mortality rates in patients with a history of MI and should not be used for the treatment of hypertension The ALLHAT study enrolled patients with hypertension and with a

known risk factor for CAD The study showed that chlorthalidone, amlodipine, and lisinopril had similar outcomes of combined fatal coronary heart disease (CHD) and nonfatal MIReaching across Arizona to provide comprehensive quality health care for those in need 57 Calcium Channel Blockers Many large trials enrolling patients with hypertension have demonstrated that CCBs have beneficial effects on composite cardiovascular outcomes or individual clinical outcomes However, most of the trials only demonstrated equivalence to the comparator antihypertensives rather than superiority Reaching across Arizona to provide comprehensive

quality health care for those in need 58 Calcium Channel Blockers Product/Guideline Updates: Consensi, a combination of amlodipine and celecoxib, is indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate Consensi is approved as tablets in amlodipine/celecoxib strengths 2.5 mg/200 mg, 5 mg/200 mg, or 10 mg/200 mg and is dosed once daily Contraindications, warnings, adverse reactions and drug interactions are consistent with the individual Reaching across Arizona to provide comprehensive 59 quality health care for those in need

products Leukotriene Modifiers Reaching across Arizona to provide comprehensive quality health care for those in need 60 Leukotriene Modifiers Class Overview: montelukast - (montelukast chewable tablet, granules & tablet; Singulair Chewable Tablet, Granules & Tablet) zafirlukast - (Accolate; zafirlukast) zileuton- (zileuton ER; Zyflo; Zyflo CR) Reaching across Arizona to provide comprehensive quality health care for those in need

61 Leukotriene Modifiers Zafirlukast, zileuton, and zileuton ER are only approved for prophylaxis and chronic treatment of asthma Montelukast is the only leukotriene modifier that is approved for asthma and allergic rhinitis and can be considered for patients with these two co-morbidities National Asthma Education and Prevention Program (NAEPP) and 2018 Global Initiative for Asthma (GINA) guidelines recommend inhaled

corticosteroids (ICS) as the cornerstone for the treatment of asthma Leukotriene modifiers are included as potential alternatives or add-on therapy in some patients GINA states that leukotriene modifiers are less effective than ICS, but may be appropriate for initial controller treatment for patients unable or Reaching across Arizona provide comprehensive unwilling to use ICS, intolerant to toICS, or who also have allergic rhinitis 62 quality health care for those in need Leukotriene Modifiers

Leukotriene modifiers are also used as add-on therapy to reduce the dose of the ICS in patients with moderate to severe asthma, and to potentially improve asthma control in patients whose asthma is not controlled with low or high doses of ICS Limited data exist to support the use of leukotriene modifiers in acute asthma The American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma, and Immunology (ACAAI), and the American Academy of Otolaryngology, Head and Neck Surgery recommend intranasal corticosteroids (INCS) as first line treatment for patients with seasonal allergic rhinitis (SAR) Montelukast is considered an alternative to first-line therapy with INCS in patients who suffer from both asthma and SAR Reaching across Arizona

to provide comprehensive quality health care for those in need 63 Leukotriene Modifiers The International Consensus Statement on Allergy and Rhinology Allergic Rhinitis guidelines state that leukotriene receptor antagonist monotherapy can be a useful alternative in patients with contraindications for INCSs and oral antihistamines Currently, high-quality comparative trials of the leukotriene modifiers are limited Montelukast is the most widely used leukotriene modifier because of its multiple indications, once daily dosing, and ease of

administration due to several different dosage forms Reaching across Arizona to provide comprehensive quality health care for those in need 64 Leukotriene Modifiers Product Updates: None Reaching across Arizona to provide comprehensive quality health care for those in need 65 Phosphate Binders Reaching across Arizona to provide comprehensive

quality health care for those in need 66 Phosphate Binders Class Overview: calcium acetate - (calcium acetate capsule & tablet; Phoslyra) ferric citrate - (Auryxia) lanthanum carbonate - (Fosrenol Chewable Tablet; Fosrenol Powder Pack; lanthanum carbonate chewable tablet) sevelamer carbonate - (Renvela Powder Pack; Renvela Tablet; sevelamer carbonate powder pack, tablet & tablet (AG)) sevelamer HCL - (Renagel) sucroferric oxyhydroxide - (Velphoro) Reaching across Arizona to provide comprehensive quality health care for those in need 67

Phosphate Binders Chronic kidney disease (CKD) affects approximately 30 million individuals in the United States Kidney function deterioration results in decline in the ability to eliminate phosphorus, resulting in hyperphosphatemia In end stage renal disease (ESRD), patients are at risk for several complications of hyperphosphatemia, including: o Renal bone disease o Soft and vascular tissue calcification o Cardiovascular disease o Increased death The National Kidney Foundation updated their guidelines in 2017 under The

Kidney Disease: Improving Global Outcomes (KDIGO) foundation Reaching across Arizona to provide comprehensive quality health care for those in need 68 Phosphate Binders Treatment of hyperphosphatemia includes the reduction of dietary phosphorus, phosphate binding therapy, and removal of phosphorus by dialysis Studies have shown control of hyperphosphatemia is critical in the

prevention and delay of renal osteodystrophy and soft tissue calcifications All phosphate binders are considered efficacious in reducing serum phosphate levels Guidelines do not strongly prefer one type of phosphate binder over another for adults Selection of an appropriate phosphate binder should be based on various clinical parameters and should be individualized to meet each patients unique medical needs Reaching across Arizona to provide comprehensive quality health care for those in need 69 Phosphate Binders Product Updates: None

Reaching across Arizona to provide comprehensive quality health care for those in need 70 Sedative Hypnotics Reaching across Arizona to provide comprehensive quality health care for those in need 71 Sedative Hypnotics Class Overview: Benzodiazepine Agents estazolam - (estazolam) flurazepam - (flurazepam) quazepam (Doral; quazepam) temazepam - (Restoril; temazepam; temazepam

7.5mg & 22.5mg) triazolam - (Halcion; triazolam) Reaching across Arizona to provide comprehensive quality health care for those in need 72 Sedative Hypnotics Class Overview: Non-Benzodiazepine Agents doxepin - (Silenor) eszopiclone - (eszopiclone; Lunesta) ramelteon - (ramelteon; Rozerem) suvorexant - (Belsomra) tasimelteon - (Hetlioz) zaleplon - (Sonata; zaleplon) zolpidem - (Ambien; Ambien CR; Edluar; Intermezzo; zolpidem;zolpidem SL; zolpidem ER; Zolpimist) Reaching across Arizona to provide comprehensive quality health care for those in need

73 Sedative Hypnotics Insomnia is a symptom complex that comprises difficulties falling asleep, staying asleep, or non-refreshing sleep in combination with daytime dysfunction or distress Non-pharmacological measures should be used first to treat insomnia The updated 2017 American Academy of Sleep Medicine (AASM) guidelines recommend psychological and behavioral strategies, as well as pharmacological interventions

The guidelines recommend that initial behavioral interventions should include stimulus control or relaxation therapy, or a combination of therapies referred to as cognitive behavioral Reaching across Arizona to provide comprehensive therapy (CBT) for insomnia 74 quality health care for those in need Sedative Hypnotics AASM guideline recommends that pharmacotherapy should be used to treat patients who failed to respond to CBT AASM recommends: o Zaleplon, triazolam, and ramelteon versus no treatment for sleep onset insomnia

o Suvorexant and doxepin over no treatment for sleep maintenance insomnia o Eszopiclone, zolpidem, and temazepam for both sleep onset and sleep maintenance insomnia o Against the use of trazodone or tiagabine for sleep onset or for sleep maintenance insomnia in adults o Against the use of OTC medications, supplements, or herbal products as

across or Arizona to provide maintenance comprehensive a treatment for sleepReaching onset sleep for chronic insomnia quality health care for those in need 75 Sedative Hypnotics Current treatment guidelines for insomnia do not recommend one agent within this class over another, suggesting treatment be

individualized o on: Choice of agent should be based Availability of other treatments options o Symptom pattern o Comorbid conditions o Treatment goals o Contraindications

o Past treatment response o o Patient preference Potential interactions with concurrent medications o Cost o

Adverse effects Reaching across Arizona to provide comprehensive quality health care for those in need 76 Sedative Hypnotics Non-24-hour sleep-wake disorder (N24SWD or non-24) is a chronic

circadian rhythm disorder that causes problems with the timing of sleep and sleep patterns. Hetlioz is only indicated for use in N24SWD With the exception of zolpidem SL, all agents should be administered immediately before going to bed or after the patient has gone to bed and experienced difficulty falling asleep Zolpidem SL should be utilized for middle of the night awakenings when the patient still has more than 4 hours before planned waking time Due to gender differences in zolpidem clearance, women generally require lower doses ofReaching zolpidem across Arizona to provide comprehensive quality health care for those in need 77 Sedative Hypnotics

Doxepin, ramelteon, and tasimelteon are the only agents in this class that are not controlled substances and are not associated with abuse or physical dependence All drugs in this class should be used at the lowest effective dose All sedative/hypnotics should be administered with caution in patients exhibiting signs and symptoms of depression Patients whose insomnia fails to remit after 7 to 10 days of treatment may need to be evaluated for other medical or psychological issues Continuous use should be avoided; patients should be encouraged to use these medications only when necessary Reaching across Arizona to provide comprehensive

quality health care for those in need 78 Sedative Hypnotics In 2016, the FDA informed healthcare professionals that concurrent use of opioids and benzodiazepines or other CNS depressants may result in serious adverse reactions such as profound sedation, respiratory depression, coma, and death Providers should limit prescribing opioids with benzodiazepines to only patients without alternative treatment options Reaching across Arizona to provide comprehensive quality health care for those in need 79

Sedative Hypnotics Treatment Updates: The FDA is requiring a boxed warning be added to the prescribing information for eszopiclone, zaleplon, and zolpidem regarding serious injuries and death from complex sleep behaviors, in addition to a contraindication in patients who have previously experienced an episode of complex sleep behavior with these medications Reaching across Arizona to provide comprehensive quality health care for those in need 80 Steroids, Topical Reaching across Arizona to provide comprehensive quality health care for those in need

81 Steroids, Topical Class Overview: Low Potency Topical Steroid Products alclometasone dipropionate (alclometasone dipropionate cream & ointment) desonide (Desonate Gel; Desowen Cream; desonide cream, lotion & ointment; Tridesilon; Verdeso) fluocinolone acetonide (Capex Shampoo; Dema-SmootheFS; fluocinolone 0.01% oil) fluocinolone acetonide/Cetaphil cleanser lotion (Xilapak Kit) fluocinolone acetonide/ urea* (NoxiPak Kit) Reaching across Arizona to provide comprehensive quality health care for those in need 82 Steroids, Topical Class Overview: Low Potency Topical Steroid Products hydrocortisone (Advanced Allergy Collection Kit, Ala-Cort, Ala-Scalp, Aquanil, Anti-Itch, Aqua Glycolic HC Kit, Beta HC,

Cortaid, Cortisone, Cortizone, Dermarest Eczema, Dermasorb HC Complete Kit, GS Anti-Itch, MiCort HC, Noble Formula HC, QC Anti-Itch, Scalacort, Scalacort-DK Kit, Scalp Relief, Scalpicin, Soothing Care, Texacort, Vanicream; hydrocortisone) hydrocortisone/aloe vera (Cortisone-10, Cortisone Plus Aloe, Nucort, QC Anti-Itch with Aloe, SM Hydrocortisone-Aloe, SM Hydrocortisone Plus; hydrocortisone/aloe vera) Reaching across Arizona to provide comprehensive quality health care for those in need 83 Steroids, Topical Class Overview: Medium Potency Topical Steroid Products betamethasone valerate - (betamethasone valerate foam; Luxiq) clocortolone pivalate - (clocortolone cream (AG); Cloderm)

fluocinolone acetonide - (fluocinolone acetonide cream, ointment & solution; Synalar Ointment & Solution) flurandrenolide - (Cordran Tape; flurandrenolide cream, lotion, lotion (AG) & ointment; Nolix) fluticasone propionate - (Cutivate Cream & Lotion; Reaching across Arizona to provide comprehensive 84 quality health care for those in need fluticasone cream, lotion & ointment) Steroids, Topical Class Overview: Medium Potency Topical Steroid Products hydrocortisone butyrate - (hydrocortisone butyrate cream, cream (AG), lotion, ointment, ointment (AG), solution & solution (AG); Locoid / Lipocream) hydrocortisone probutate - (Pandel) hydrocortisone valerate - (hydrocortisone valerate cream & ointment)

mometasone furoate - (Elocon Cream & Ointment; mometasone furoate cream, ointment & solution ) prednicarbate - (Dermatop; prednicarbate cream & ointment) Reaching across Arizona to provide comprehensive quality health care for those in need 85 Steroids, Topical Class Overview: High Potency Topical Steroid Products amcinonide - (amcinonide cream & lotion) betamethasone dipropionate - (betamethasone dipropionate cream, gel, lotion & ointment; Sernivo Spray) betamethasone valerate - (betamethasone valerate cream & ointment) betamethasone dipropionate augmented cream (Diprolene AF) desoximetasone - (desoximetasone cream, gel & ointment; Topicort Ointment & Spray) diflorasone diacetate - (diflorasone diacetate cream & ointment)

fluocinonide - (fluocinonide cream, gel, ointment & solution; Vanos) Reaching across Arizona to provide comprehensive quality health care for those in need 86 Steroids, Topical Class Overview: High Potency Topical Steroid Products fluocinonide/emollient - (fluocinonide emollient) halcinonide - (Halog Cream & Ointment) triamcinolone acetonide/dimethicone - (Ellzia Pak) triamcinolone acetonide/silicones - (DermacinRx Silazone; SilazoneII) triamcinolone acetonide - (Kenalog Aerosol; triamcinolone acetonide aerosol, cream, lotion & ointment; Trianex Ointment) triamcinolone acetonide/dimethicone/silicones - (DermacinRx Silapak; triamcinolone acetonide/dimethicone) triamcinolone/emollient - (Dermasorb TA) Reaching across Arizona to provide comprehensive quality health care for those in need

87 Steroids, Topical Class Overview: Very High Potency Topical Steroid Products clobetasol propionate - (clobetasol lotion; clobetasol propionate cream, gel, ointment, solution, spray & spray (AG); clobetasol shampoo; Clobex Lotion, Shampoo & Spray; Olux; Temovate Cream) clobetasol propionate/clobetasol propionate/emollient (clobetasol propionate foam) clobetasol propionate/emollient - (clobetasol propionate/emollient ) clobetasol propionate/skin cleanser - (Clodan Kit) diflorasone diacetate/emollient - (Apexicon E) Reaching across Arizona to provide comprehensive quality health care for those in need 88

Steroids, Topical Class Overview: Very High Potency Topical Steroid Products halobetasol propionate - (halobetasol propionate cream & ointment; Ultravate Lotion) halobetasol/lactic acid - (Ultravate X Pac Cream & Ointment) Halobetasol propionate foam - (Lexette) halobetasol propionate lotion - (Bryhali) Reaching across Arizona to provide comprehensive quality health care for those in need 89 Steroids, Topical

Topical corticosteroids are used in a variety of inflammatory skin conditions Atopic dermatitis (AD) is a chronic, inflammatory dermatologic condition and is often referred to as eczema AD commonly occurs in patients affected by asthma and/or allergic rhinitis and is associated with elevated serum IgE levels AD can present at any age, but prevails most frequently in children Psoriasis is another inflammatory skin condition, with plaque psoriasis being the most common type frequently forming on the elbows, knees, lower back, and scalp Controlling symptoms of plaque psoriasis typically requires lifelong therapy Reaching across Arizona to provide comprehensive quality health care for those in need

90 Steroids, Topical Seborrheic dermatitis is an inflammatory disorder affecting areas of the head and trunk, where sebaceous glands are most prominent Pharmacotherapy choices for these conditions include emollients and topical corticosteroids Emollients remain the cornerstone of any AD treatment regimen

Topical corticosteroids are the standard of care to which other treatments are compared The selection of medication and potency should depend on: o Medication efficacy o Severity of disease o Location and surface area of affected skin

o Intended duration of treatment Reaching across Arizona to provide comprehensive quality health care for those in need 91 Steroids, Topical Medication vehicle o Patient preference o Patient age In short-term durations of treatment, high potency medications have greater efficacy when compared to less potent medications, but with an increased risk in side effects Increased incidences of adverse dermatologic reactions are positively correlated with the medications frequency and duration of use True efficacy and risk of long-term topical corticosteroid use

across Arizona to provide comprehensive is unknown becauseReaching most clinical trials only involved shortquality health care for those in need o 92 Steroids, Topical Treatment guidelines from the American Academy of Dermatology recommend that continued therapy be supervised and a gradual reduction in utilization is appropriate once a clinical response is demonstrated There are differing compendia listings for corticosteroid potencies

Efficacy of topical corticosteroids is relative to their potency, but individual agents within a potency category are not distinguishable from each other Reaching across Arizona to provide comprehensive quality health care for those in need 93 Steroids, Topical Product/Guideline Updates: Bryhali is a corticosteroid lotion indicated for the topical treatment of plaque psoriasis in adults It is approved as a 0.01% halobetasol propionate lotion available in 45g, 60g, and 100g tubes It is dosed as a thin layer applied topically to affected area(s) once daily for up to 8 consecutive weeks Warnings and adverse reactions are similar to other halobetasol products Reaching across Arizona to provide comprehensive

quality health care for those in need 94 Steroids, Topical Product/Guideline Updates: Merck has made a business decision to discontinue Elocon 0.1% in 15g and 50g tubes. Other formulations of mometasone 0.1% cream are available Janssen announced the discontinuation of Nizoral 2% shampoo (ketoconazole). The last production was in October 2018 with an expiration date of September 2020 Reaching across Arizona to provide comprehensive quality health care for those in need 95 New Drug Reviews

Hind Douiki, Pharm.D. Reaching across Arizona to provide comprehensive quality health care for those in need 96 New Products Mayzent (siponimod) Rocklatan (netarsudil/latanoprost) Mavenclad (cladribine) Evenity (romosozumab-aqqg)

Diacomit (stiripentol) Skyrizi (risankizumab) Reaching across Arizona to provide comprehensive quality health care for those in need 97 New Products Cutaquig (immune globulin) Egaten (triclabendazole) Sunosi (solriamfetol) Rinvoq (upadacitinib) Vyndamax (tafamidis)

Reaching across Arizona to provide comprehensive quality health care for those in need 98 Mayzent (siponimod) Indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease Before initiation of treatment with Mayzent, CYP2C9 Genotype Determination Test must be completed to determine CYP2C9 genotype The following must also be obtained and assessed: o

o o o o o Complete Blood Count Ophthalmic evaluation Cardiac evaluation Current or prior medications Vaccinations Liver function tests Reaching across Arizona to provide comprehensive quality health care for those in need 99 Mayzent (siponimod)

Titration is required for treatment initiation and the dose depends on the genotype It is available as 0.25 mg and 2 mg tablets Contraindications: o Patients with a CYP2C9*3/*3 genotype o In the last 6 months, patient experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure o Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker Reaching across Arizona to provide comprehensive quality health care for those in need 100

Mayzent (siponimod) Warnings: o Infections o Macular edema o Bradyarrhythmia and atrioventricular conduction delays o Respiratory effects o Liver injury o Increased blood pressure o Fetal risk Most common adverse reactions (incidence greater than 10%): o Headache o Hypertension o Transaminase increases Reaching across Arizona to provide comprehensive quality health care for those in need

101 Mayzent (siponimod) Drug interactions: o Antineoplastics o Immunumodulators o Immunosuppressives o Antiarrhythmics o QT-prolonging drugs o Drugs that may decrease heart rate o Vaccinations o CYP2C9 and CYP3A4 inhibitors o CYP2C9 and CYP3A4 inducers Reaching across Arizona to provide comprehensive quality health care for those in need

102 Mayzent (siponimod) No comparative data are available The FDA approval of Mayzent was based on the randomized, double-blind, placebo-controlled phase III EXPAND trial The efficacy and safety of Mayzent versus placebo was compared in 1,651 subjects with secondary progressive multiple sclerosis (SPMS)

Inclusion criteria also included the following: evidence of disability progression in the prior 2 years, no evidence of relapse in 3 months prior to study enrollment, and an Expanded Disability Status Scale (EDSS) score of 36.5 at study entry Evaluations were performed at screening, every 3 months during the study, and at the time of a suspected relapse; MRI evaluations were performed at screening and every 12 months Reaching across Arizona to provide comprehensive quality health care for those in need 103 Mayzent (siponimod) Mayzent significantly reduced the risk of three-month confirmed disability progression (which was the primary endpoint; 21% reduction versus placebo, p=0.013; 33% reduction versus placebo in patients with relapse

activity in the two years prior to screening, p=0.01) Mayzent also reduced the annualized relapse rate by 55% Reaching across Arizona to provide comprehensive quality health care for those in need 104 Rocklatan (netarsudil/latanoprost) Indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension Dose is one drop into the affected eye(s) once daily in the evening Warnings: o Pigmentation

o Eyelash changes o Intraocular inflammation o Macular edema Reaching across Arizona to provide comprehensive quality health care for those in need o Herpetic and bacterial keratitis 105 Rocklatan (netarsudil/latanoprost)

The most common adverse reaction is conjunctival hyperemia (59%) Other common adverse reactions were instillation site pain (20%), corneal verticillata (15%), and conjunctival hemorrhage (11%) The FDA approval of Rocklatan was based on two Phase III registration trials, MERCURY 1 and MERCURY 2 Studies 301 and 302 enrolled subjects with IOP < 36 mmHg and compared IOP lowering effect of Rocklatan dosed once daily to individually administered netarsudil 0.02% once daily and latanoprost 0.005% once daily The treatment duration was 12 months for MERCURY 1; 3 months for MERCURY 2 Reaching across Arizona to provide comprehensive quality health care for those in need 106 Rocklatan (netarsudil/latanoprost)

In these studies, Rocklatan achieved its primary 90-day efficacy endpoint as well as positive 12-month safety and efficacy results Rocklatan demonstrated statistically greater IOP reduction over latanoprost and netarsudil at every measured time point More than 60% of patients taking Rocklatan in the two MERCURY studies achieved an IOP reduction of 30% or more; nearly twice that achieved by patients taking latanoprost alone Rocklatan also helped more patients get to low target pressures Nearly twice as many patients taking Rocklatan reached 16 mmHg or lower and nearly three times as many reached 14 mmHg or lower compared to latanoprost Reaching across Arizona to provide comprehensive quality health care for those in need

107 Mavenclad (cladribine) Indicated for the treatment of relapsing forms of MS, to include relapsing-remitting disease and active secondary progressive disease in adults Because of its safety profile, use of Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS Not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile Reaching across Arizona to provide comprehensive quality health care for those in need 108

Mavenclad (cladribine) Assessments prior to starting each Mavenclad treatment course: o Cancer Screening o Pregnancy o Complete Blood Count (CBC) with differential including lymphocyte count o Infections o Vaccinations o A baseline MRI must be obtained prior to the first treatment course because of the risk of progressive multifocal leukoencephalopathy o Liver function Reaching across Arizona to provide comprehensive quality health care for those in need 109

Mavenclad (cladribine) The recommended cumulative dosage is 3.5 mg per kg body weight administered orally and divided into 2 yearly treatment courses of 1.75 mg per kg per treatment course It is available as 10 mg tablets Reaching across Arizona to provide comprehensive quality health care for those in need 110 Mavenclad (cladribine) Contraindications: o Patients with current malignancy o Pregnant women o Women and men of reproductive potential who do not plan to use effective contraception during Mavenclad therapy and for 6 months after the last dose

o HIV infection o Active chronic infections o History of hypersensitivity to cladribine o Women intending to breastfeed on a Mavenclad treatment and for 10 days after the last dose Reaching across Arizona to provide comprehensive quality health care for those in need 111 Mavenclad (cladribine) Carries a boxed warning regarding malignancies and risk of teratogenicity Other warnings:

o Lymphopenia o Infections o Hematologic toxicity o Graft-versus-host-disease with blood transfusion o Liver injury Most common adverse reactions (incidence > 20%): o Upper respiratory tract infection o Headache o Lymphopenia Reaching across Arizona to provide comprehensive quality health care for those in need 112 Mavenclad (cladribine)

No comparative data are available The FDA approval of Mavenclad was based on a randomized, double-blind, placebo-controlled study in patients with relapsing forms of MS Patients were required to have at least 1 relapse in the previous 12 months The trial enrolled 1,326 patients who were randomized to receive either placebo or a cumulative oral dosage of Mavenclad 3.5 mg per kg or 5.25 mg per kg body weight over the 96-week study period in 2 treatment courses Patients randomized to the 3.5 mg per kg cumulative dose received a first treatment course at Weeks 1 and 5 of the first year and a Reaching across Arizona to provide comprehensive 113

care for those in need second treatment coursequality at health Weeks 1 and 5 of the second year Mavenclad (cladribine) Patients randomized to the 5.25 mg per kg cumulative dose received additional treatment at Weeks 9 and 13 of the first year Higher cumulative doses did not add any clinically meaningful benefit, but were associated with a higher incidence in grade 3

lymphopenia or higher The primary outcome was the annualized relapse rate (ARR) Mavenclad 3.5 mg per kg cumulative dose significantly lowered the ARR; patients experienced a 58% relative reduction compared to placebo (0.14 vs. 0.33, p<0.001) In addition, 81% of patients were free of relapses after two years of short-course oral treatment with Mavenclad, compared to 63% of patients who receivedReaching placebo (p<0.05) across Arizona to provide comprehensive quality health care for those in need 114 Mavenclad (cladribine) Patients treated with Mavenclad had a 33% reduction in risk

of 3-month confirmed disability progression as measured by EDSS compared to placebo (p<0.05) Patients taking Mavenclad experienced a lower median number of T1-weighted gadolinium-enhanced brain lesions and new or enlarging T2 brain lesions compared to patients with placebo (0 vs. 0.33 and 0 vs. 0.67 p<0.001) Reaching across Arizona to provide comprehensive quality health care for those in need 115 Evenity (romosozumab-aqqg) Indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to

other available osteoporosis therapy The anabolic effect of Evenity wanes after 12 monthly doses of therapy; therefore, the duration of Evenity use should be limited to 12 monthly doses Two separate syringes and subcutaneous injections are needed to administer the total dose of 210 mg of Evenity every month Reaching across Arizona to provide comprehensive quality health care for those in need Available as 105 mg/1.17 mL prefilled syringes 116 Evenity (romosozumab-aqqg)

Patients should be adequately supplemented with calcium and vitamin D during treatment with Evenity Contraindicated in patients with hypocalcemia Carries a boxed warning regarding potential risk of myocardial infarction, stroke, and cardiovascular death Other warnings: o Major Adverse Cardiac Events (MACE) o Hypersensitivity reactions o Hypocalcemia o Osteonecrosis of the jaw o Atypical femoral fracture Reaching across Arizona to provide comprehensive quality health care for those in need 117 Evenity (romosozumab-aqqg)

The most common adverse reactions ( 5%) reported in clinical trials were arthralgia and headache The FDA approval of Evenity was based on two phase III trials, FRAME and ARCH FRAME was a randomized, double-blind, placebo-controlled study that evaluated 7,180 postmenopausal women with osteoporosis The study evaluated the efficacy of Evenity treatment (at 210 mg administered monthly), compared with placebo, in reducing the incidence of new vertebral fractures through 12 months The study also evaluated the efficacy of treating with Evenity for 12 months followed by Prolia for 12 months, compared with placebo followed by Prolia, in reducing the incidence of new vertebral fractures Reaching across Arizona to provide comprehensive

through 24 months quality health care for those in need 118 Evenity (romosozumab-aqqg) Treatment with Evenity resulted in a significant reduction of new vertebral fracture at 12 months compared to placebo This significant reduction in fracture risk persisted through the second year in women who received Evenity during the first year and transitioned to Prolia compared to those who transitioned from placebo to Prolia

In addition, Evenity significantly increased bone mineral density (BMD) at the lumbar spine, total hip and femoral neck compared to placebo at 12 months Following the transition from Evenity to Prolia at month 12, BMD continued to increase through month 24 Reaching across Arizona to provide comprehensive quality health care for those in need 119 Evenity (romosozumab-aqqg)

ARCH was a randomized, double-blind, alendronate-controlled study of Evenity in 4,093 postmenopausal women with osteoporosis and previous fracture history This event-driven study evaluated 12 months of Evenity treatment followed by at least 12 months of alendronate treatment, compared with alendronate treatment alone The objective was to assess Evenitys efficacy in reducing the risk of clinical fracture through the primary analysis period and the incidence of new vertebral fracture at 24 months Treatment with Evenity for 12 months followed by 12 months of alendronate significantly reduced the incidence of new vertebral fracture at 24 months Reaching across Arizona to provide comprehensive quality health care for those in need 120 Evenity (romosozumab-aqqg) Evenity followed by alendronate significantly reduced

the risk of clinical fracture after a median follow-up of 33 months Evenity also significantly increased BMD at the lumbar spine, total hip and femoral neck at 12 months compared to alendronate Reaching across Arizona to provide comprehensive quality health care for those in need 121 Diacomit (stiripentol) Indicated for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older taking clobazam There are no clinical data to support the use of Diacomit as monotherapy in Dravet syndrome

Dose is 50 mg/kg/day by mouth in 2 or 3 divided doses Available as 250 mg or 500 mg capsules and 250 mg or 500 mg powder for oral suspension Reaching across Arizona to provide comprehensive quality health care for those in need 122 Diacomit (stiripentol) Warnings: o Somnolence o Decreased appetite and decreased weight o Neutropenia and thrombocytopenia o Withdrawal o Risks in patients with phenylketonuria o Suicidal behavior and ideation Reaching across Arizona to provide comprehensive quality health care for those in need

123 Diacomit (stiripentol) Adverse reactions that occurred in at least 10% of Diacomittreated patients and more frequently than with placebo: o Hypotonia o Somnolence o Nausea o Decreased appetite o Tremor o Agitation o Dysarthria o Ataxia o Insomnia o Weight decrease Reaching across Arizona to provide comprehensive

quality health care for those in need 124 Diacomit (stiripentol) No comparative data are available The FDA approval of Diacomit was based on two multicenter placebocontrolled trials, Study 1 and, Study 2, which enrolled a combined total of 64 subjects The primary efficacy endpoint in both trials was the responder rate

This was defined as a patient who experienced a greater than 50% decrease in the frequency (per 30 days) of generalized clonic or tonic-clonic seizures during the double-blind treatment period compared to the 4-week baseline period In Study 1, the responder rate for patients receiving Diacomit was 71%, compared to 5% for patients receiving placebo In Study 2, the responder rate for patients receiving Diacomit was 67%, compared to 9.1% for patients receiving placebo Reaching across Arizona to provide comprehensive quality health care for those in need 125

Skyrizi (risankizumab-rzaa) Indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy Dosage is 150 mg (two 75 mg injections) administered by subcutaneous injection at Week 0, Week 4 and every 12 weeks thereafter Warnings o Infections o Tuberculosis o Immunizations Reaching across Arizona to provide comprehensive quality health care for those in need 126

Skyrizi (risankizumab-rzaa) Most common adverse reactions ( 1%): o Upper respiratory infections o Headache o Fatigue o Injection site reactions o Tinea infections The safety and efficacy of Skyrizi in adults with moderate to severe plaque psoriasis was assessed across four randomized, placebo and/or active-controlled pivotal studies: ultIMMa-1, ultIMMa-2, IMMhance and IMMvent Reaching across Arizona to provide comprehensive quality health care for those in need 127

Skyrizi (risankizumab-rzaa) The co-primary endpoints of these studies were Psoriasis Area and Severity Index (PASI 90) and static Physician Global Assessment [sPGA] score of clear or almost clear [sPGA 0/1] at 16 weeks versus placebo In ULTIMMA-1 and ULTIMMA-2, 997 subjects were randomized to the Skyrizi 150 mg group, to the placebo group, and to the biologic active control group Subjects received treatment at Weeks 0, 4, and every 12 weeks thereafter In ultIMMa-1 and ultIMMa-2 at 16 weeks, PASI 90 was achieved in

75 percent of patients treated with Skyrizi, compared to 5 and 2 percent receiving placebo, (p<0.001) Reaching acrossrespectively Arizona to provide comprehensive 128 quality health care for those in need Skyrizi (risankizumab-rzaa) PASI 100 was achieved in 36 and 51 percent of patients treated with Skyrizi, compared to 0 and 2 percent receiving placebo, respectively (p<0.001) At 52 weeks, 82 and 81 percent of patients treated with Skyrizi

achieved PASI 90, and 56 and 60 percent achieved PASI 100, respectively (p<0.001) An integrated analysis of ultIMMa-1 and ultIMMa-2 showed most patients treated with Skyrizi who achieved PASI 90 and PASI 100 at week 16 maintained this response at 52 weeks (88 and 80 percent, respectively) Reaching across Arizona to provide comprehensive quality health care for those in need 129 Skyrizi (risankizumab-rzaa) IMMHANCE enrolled 507 subjects who were randomized to Skyrizi 150 mg and to placebo Participants received treatment at Weeks 0, 4, and every 12 weeks thereafter At Week 16, Skyrizi was superior to placebo on the coprimary endpoints of sPGA 0 or 1 (84% Skyrizi and 7%

placebo) and PASI 90 (73% Skyrizi and 2% placebo) The respective response rates for Skyrizi and placebo at Week 16 were: sPGA 0 (46% Skyrizi and 1% placebo); PASI 100 (47% Skyrizi and 1% placebo); and PASI 75 (89% Skyrizi and 8% placebo) Reaching across Arizona to provide comprehensive quality health care for those in need 130 Skyrizi (risankizumab-rzaa) IMMvent was a multinational, phase 3, randomized, double-blind, double-dummy, active-controlled trial

In Part A, patients were randomized 1:1 to receive Skyrizi 150 mg at weeks 0 and 4 or adalimumab 80 mg at week 0 and 40 mg every 2 weeks from week 1 to week 15 In Part B (weeks 16-44), patients initially randomized to receive adalimumab who achieved PASI 50 to <90 at week 16 were rerandomized 1:1 to receive Skyrizi 150 mg at weeks 16, 20, and 32 or ADA 40 mg every 2 weeks up to week 41 Skyrizi demonstrated superiority versus adalimumab, with 72 percent of patients achieving PASI 90 compared to 47 percent of patients treated with adalimumab at Week 16 (p<0.001) Reaching across Arizona to provide comprehensive quality health care for those in need 131 Skyrizi (risankizumab-rzaa) Following re-randomization at Week 16, 66 percent of patients who started on adalimumab and switched to Skyrizi achieved PASI 90, compared to 21

percent who continued on adalimumab at Week 44 (p<0.001) The co-primary endpoints of sPGA 0/1 and PASI 90 at Week 16 were met (p<0.001) Reaching across Arizona to provide comprehensive quality health care for those in need 132 Cutaquig (immune globulin) Indicated for treatment of primary humoral immunodeficiency (PI) in adults The dose is to be individualized based on the patients pharmacokinetic and clinical response

Trough Serum IgG levels should be monitored regularly to guide subsequent dose adjustments as needed Contraindications: o Patients who have had an anaphylactic or severe systemic reaction to human immune globulin or to any of the components of Cutaquig o IgA-deficient patients with antibodies against IgA and a history of hypersensitivityReaching to human globulin treatment across Arizona to provide comprehensive 133 quality health care for those in need Cutaquig (immune globulin)

Carries a boxed warning regarding the risk of thrombosis Other warnings: o Hypersensitivity o Falsely elevated glucose readings o Aseptic Meningitis Syndrome o Renal dysfunction/failure o Hemolysis o Transfusion-related acute lung injury o Transmittable infectious agents o Interference with laboratory tests Reaching across Arizona to provide comprehensive quality health care for those in need 134 Cutaquig (immune globulin)

The most common adverse reactions observed in 5% of study subjects: o Local infusion site adverse reactions o Headache o Fever o Diarrhea o Dermatitis o Asthma o Skin abrasion Reaching across Arizona to provide comprehensive quality health care for those in need 135 Cutaquig (immune globulin) FDA approval was based on a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with Primary Immune Deficiency to

investigate the efficacy, safety and tolerability of Cutaquig The trial included 61 (adult and pediatric) patients who were previously treated with IVIG Results: o No serious bacterial infections developed during the study o The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57)

o 18.0% of patients experienced 14 mild or moderate systemic adverse events related to Cutaquig o In 77% of infusions, no infusion site reactions were observed; 0.3% of the reactions were deemed severe Reaching across Arizona to provide comprehensive quality health care for those in need 136 Egaten (triclabendazole)

Indicated for the treatment of fascioliasis in patients 6 years of age and older Dosage is 2 doses of 10 mg/kg given 12 hours apart; it is available as 250 mg tablets Contraindicated in patients with known hypersensitivity to triclabendazole, other benzimidazole derivatives or any of the excipients Carries a QT Prolongation warning Most common adverse reactions (greater than 2%) are abdominal pain, hyperhidrosis, nausea, decreased appetite, headache, urticaria, diarrhea, vomiting, musculoskeletal chest pain, and pruritus Reaching across Arizona to provide comprehensive quality health care for those in need

137 Egaten (triclabendazole) An open label, randomized trial, conducted in Vietnam compared the efficacy of Egaten to oral artesunate 100 (pediatric and adult) patients with acute symptomatic fascioliasis were randomized At 3 months after treatment, 92% and 76% of patients in the Egaten and artesunate arms respectively, reported no clinical symptoms In addition to this trial, the clinical development program of Egaten

for the treatment of fascioliasis included 6 non-randomized, open label studies similar in design These were performed in Cuba, Bolivia, Peru, Chile, and Iran in a total of 245 adult and Reaching pediatric patients with stool-confirmed across Arizona to provide comprehensive quality health care for those in need fascioliasis 138 Egaten (triclabendazole)

The studied Egaten doses ranged from 5 mg/kg to 20 mg/kg administered on days 1-3 Cure was defined as absence of Fasciola eggs in the stool based on the Kato-Katz method at Day 60 in patients who were positive at baseline Across these studies, there was a finding of a dose response Specifically, the Day 60 cure rate was highest for the 20 mg/kg dose, which was given in 2 divided doses, followed by cure rates of 88%, 80% and 50% in the 15 mg/kg, 10 mg/kg, and 5 mg/kg dose groups, respectively Reaching across Arizona to provide comprehensive quality health care for those in need 139 Sunosi (solriamfetol)

Indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA) Starting dose for patients with narcolepsy and with OSA is 75 mg and 37.5 mg once daily, respectively; maximum dose is 150 mg once daily Available as 75 mg and 150 mg tablets Contraindications: o Concurrent treatment with a monoamine oxidase inhibitor (MAOI) o Use of an MAOI within the preceding 14 days Warnings: o Blood pressure and heart rate increases o Psychiatric symptoms Reaching across Arizona to provide comprehensive quality health care for those in need

140 Sunosi (solriamfetol) Most common adverse reactions ( 5% and greater than placebo): o o o o o Headache

Nausea Decreased appetite Insomnia Anxiety No comparative data are available For narcolepsy, the efficacy of Sunosi was demonstrated in a 12-week, multi-center, randomized, double-blind, placebo-controlled, parallelgroup study in adult patients with a diagnosis of narcolepsy A total of 239 patients were randomized to receive Sunosi 75 mg, 150 mg, or 300 mg, or placebo once daily Reaching across Arizona to provide comprehensive quality health care for those in need 141 Sunosi (solriamfetol)

Wakefulness and sleepiness were assessed using the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS) The co-primary efficacy endpoints were change from baseline in MWT and ESS at Week 12. Compared to the placebo group, patients randomized to 150 mg Sunosi showed statistically significant improvements on the MWT (treatment effect difference: 7.7 minutes) and on the ESS (treatment effect difference: 3.8 points) at Week 12 These effects were apparent at Week 1 and consistent with the results at Week 12 Reaching across Arizona to provide comprehensive quality health care for those in need 142 Sunosi (solriamfetol)

For OSA, the efficacy of Sunosi was demonstrated in a 12-week multi-center, randomized, double-blind, placebo-controlled study in adults The co-primary efficacy endpoints were change from baseline in MWT and ESS at Week 12 A total of 476 patients with OSA were randomized to receive Sunosi 37.5 mg, 75 mg, 150 mg, or 300 mg, or placebo once daily Compared to the placebo group, patients randomized to 37.5 mg, 75 mg, and 150 mg Sunosi showed statistically significant improvements on the

MWT (treatment effect difference: 4.5 minutes, 8.9 minutes, and 10.7 minutes respectively) and ESS (treatment effect difference: 1.9 points, 1.7 points, and 4.5 points respectively) at Week 12 These effects were apparent at Week 1 and consistent with the results at Week 12 Reaching across Arizona to provide comprehensive quality health care for those in need 143 Sunosi (solriamfetol)

For maintenance of efficacy in narcolepsy and OSA, Sunosi was assessed in two randomized-withdrawal, placebo-controlled studies, Study 3 and Study 4 Study 3 was a 6-week, multi-center, double-blind, placebocontrolled, randomized-withdrawal study in 174 adult patients with a diagnosis of OSA The co-primary efficacy endpoints were change from the beginning to the end of the randomized withdrawal period in MWT and ESS Patients were started on Sunosi 75 mg once daily, and were titrated to the maximum tolerable dose between 75 mg and 300 mg per day Reaching across Arizona to provide comprehensive quality health care for those in need 144 Sunosi (solriamfetol)

124 patients who reported much or very much improvement on the PGIc and who showed improvements on the MWT and ESS entered a double-blind withdrawal phase and were randomized 1:1 to either continue Sunosi at the dose received in the stable-dose phase or switch to placebo Compared to patients who remained on Sunosi, patients randomized to placebo experienced statistically significant worsening of sleepiness as measured by the MWT and ESS Reaching across Arizona to provide comprehensive quality health care for those in need 145 Sunosi (solriamfetol)

Study 4 was a 52-week, open-label study in 638 patients with either narcolepsy or OSA who had completed a prior trial Patients were started on Sunosi 75 mg once daily, and were titrated to the maximum tolerable dose between 75 mg and 300 mg per day Patients remained on this dose during a subsequent open-label treatment period of either 38 (for patients previously enrolled in Study 1 or Study 2) or 50 weeks (all others) 282 patients (79 with narcolepsy; 203 with OSA) entered the randomized-withdrawal period Patients were randomized 1:1 to either continue to receive Sunosi at the dose received in the maintenance phase or to switch to Reaching across Arizona to provide comprehensive

146 quality health care for those in need placebo. Sunosi (solriamfetol) The primary efficacy endpoint was change from the beginning to the end of the randomized-withdrawal period in ESS Compared to patients who remained on Sunosi, patients randomized to placebo experienced statistically significant worsening of sleepiness as measured by the ESS Reaching across Arizona to provide comprehensive quality health care for those in need 147 Rinvoq (upadacitinib)

Indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate (MTX) Use of Rinvoq in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended Dose is 15 mg once daily; it is available as 15 mg extended-release tablets May be used as monotherapy or in combination with MTX or other nonbiologic DMARDs Interruption, or initiation avoidance, should occur if absolute lymphocyte

count <500 cells/mm3, absolute neutrophil count <1000 cells/mm3, or Reaching across Arizona to provide comprehensive hemoglobin level <8 g/dL 148 quality health care for those in need Rinvoq (upadacitinib) Boxed warnings: o Serious infections o Malignancy o Thrombosis Additional warnings: o Serious infections o Malignancy

o Thrombosis o Gastrointestinal perforations o Laboratory parameters o Embryo-fetal toxicity o Vaccination Reaching across Arizona to provide comprehensive quality health care for those in need 149 Rinvoq (upadacitinib) Adverse reactions (greater than or equal to 1%): o Upper respiratory tract infections o Nausea

o Cough o Pyrexia Drug interactions: o Should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors o Coadministration with strong CYP3A4 inducers is not recommended Reaching across Arizona to provide comprehensive quality health care for those in need 150

Rinvoq (upadacitinib) The FDA approval of Rinvoq was based on data from the SELECT program, with approximately 4,400 patients evaluated across all treatment arms in five studies The studies include assessments of efficacy, safety and tolerability across a variety of RA patients, including those who failed or were intolerant to biologic DMARDs and who were nave or inadequate responders to MTX Across the SELECT Phase 3 studies, Rinvoq met all primary and ranked secondary endpoints Reaching across Arizona to provide comprehensive quality health care for those in need 151 Rinvoq (upadacitinib)

In SELECT-EARLY, 52 percent of MTX-nave patients treated with Rinvoq 15 mg achieved ACR50 vs 28 percent treated with MTX at week 12 In SELECT-MONOTHERAPY, 68 percent of MTX-IR patients treated with Rinvoq 15 mg achieved ACR20 vs 41 percent treated with continued MTX at week 14 In SELECT-COMPARE, 71 percent of MTX-IR patients treated with Rinvoq 15 mg plus MTX achieved ACR20 vs 36 percent treated with placebo plus MTX at week 12 In SELECT-NEXT, 64 percent of csDMARD-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 36 percent treated with placebo plus csDMARDs at week 12

Reaching across Arizona to provide comprehensive quality health care for those in need 152 Rinvoq (upadacitinib) In SELECT-BEYOND, 65 percent of biologicIR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 28 percent treated with placebo plus csDMARDs at week 12 Reaching across Arizona to provide comprehensive quality health care for those in need 153 Vyndamax (tafamidis)

Indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTRCM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization Dose is 61 mg orally once daily; it is available as 61 mg capsules Vyndamax and Vyndaquel are not substitutable on a per mg basis In clinical trials, the frequency of adverse events was similar to placebo, and similar proportions discontinued the study drug due to an adverse event Reaching across Arizona to provide comprehensive quality health care for those in need 154 Vyndamax (tafamidis)

There are no comparative data available The FDA approval was based on a multicenter, international, randomized, double-blind, placebo-controlled study in 441 patients with wild type or hereditary ATTR-CM Patients were randomized in a 1:2:2 ratio to receive Vyndaqel 20 mg, Vyndaqel 80 mg, or matching placebo once daily for 30 months, in addition to standard of care Treatment assignment was stratified by the presence or absence of a variant TTR genotype as well as baseline disease severity (NYHA Class) Transplant patients were excluded from this study Reaching across Arizona to provide comprehensive

quality health care for those in need 155 Vyndamax - Tafamidis The analysis demonstrated a significant reduction in allcause mortality and frequency of cardiovascular-related hospitalizations in the pooled Vyndaqel 20 mg and 80 mg arms versus placebo Analysis of the individual components of the primary analysis (all-cause mortality and cardiovascular-related hospitalizations) also demonstrated significant reductions for Vyndaqel versus placebo Reaching across Arizona to provide comprehensive quality health care for those in need 156

Executive Session Reaching across Arizona to provide comprehensive quality health care for those in need 157 Public Therapeutic Class Votes Reaching across Arizona to provide comprehensive quality health care for those in need 158 Biosimilar Update Reaching across Arizona to provide comprehensive

quality health care for those in need 159 Biosimilar Update Herceptin o Herzuma (trastuzumab-pkrb): FDA approved December 2018; anticipated availability is currently unknown o Ogivri (trastuzumab-dkst): FDA approved December 2017; anticipated availability is currently unknown o Ontruzant (trastuzumab-dttb): FDA approved January 2019; availability anticipated in June 2019 o Trazimera (trastuzumab-qyyp): FDA approved March 2019; anticipated availability is currently unknown o Kanjinti (Trastuzumab-Anns): available Reaching across Arizona to provide comprehensive quality health care for those in need

160 Biosimilar Update Avastin o Zirabev (bevacizumab-bvzr): FDA approved June 2019; anticipated availability is currently unknown o Mvasi (Bevacizumab-awwb): available As a reminder per AHCCCS Policy 310-V: AHCCCS Contractors shall not transition to a biosimilar drug until AHCCCS has determined that the biosimilar drug is overall more cost-effective to the state than the continued use of the brand name drug. Reaching across Arizona to provide comprehensive quality health care for those in need 161 P&T Meeting Dates

2020 Meeting Dates: o January 22, 2020 o May 19 and 29, 2020 Reaching across Arizona to provide comprehensive quality health care for those in need 162

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