The medical letter on drugs and therapeutics march 2 2015

The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 57 ISSUE ISSUE No 1433 1463 Volume 56 March 2, 2015 IN THIS ISSUE Suvorexant (Belsomra) for Insomnia p 29 Ceftolozane/Tazobactam (Zerbaxa) – A New Intravenous Antibiotic p 31 An Inhaled Insulin (Afrezza) p 34 Tavaborole Topical Solution (Kerydin) for Onychomycosis p 35 Correction: Secondary Prevention of Stroke p 36 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with U.S and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 57 ISSUE ISSUE No 1433 1463 Volume 56 ▶ March 2, 2015 Take CME Exams ALSO IN THIS ISSUE Ceftolozane/Tazobactam (Zerbaxa) - A New Intravenous Antibiotic p 31 An Inhaled Insulin (Afrezza) p 34 Tavaborole Topical Solution (Kerydin) for Onychomycosis p 35 Correction: Secondary Prevention of Stroke p 36 Suvorexant (Belsomra) for Insomnia The FDA has approved suvorexant (Belsomra – Merck), the first orexin receptor antagonist to become available in the US, for treatment of sleep-onset and/or sleep-maintenance insomnia Pronunciation Key Belsomra: bel som' Suvorexant: soo" voe rex' ant DRUGS FOR INSOMNIA — Benzodiazepine receptor agonists, benzodiazepines, the melatonin receptor agonist ramelteon (Rozerem, and generics), and low doses of the antidepressant doxepin (Silenor, and generics) are effective and generally safe for treatment of insomnia Benzodiazepine receptor agonists such as zolpidem (Ambien, and others) are the most widely prescribed hypnotics in the US, but they can impair next-day driving ability, increase the risk of falls in the elderly, and rarely cause anterograde amnesia, hallucinations, and complex sleep-related behaviors that occur without conscious awareness Over-thecounter antihistamines marketed as “sleep-aids” are also widely used, but they can cause next-day sedation, impairment of performance skills such as driving, and troublesome anticholinergic effects.1 MECHANISM OF ACTION — Orexin neurons are active during wakefulness and silent during sleep Signaling of orexin neuropeptides sustains wakefulness.2 Loss of orexin signaling has been associated with narcolepsy, which is characterized by excessive daytime sleepiness, cataplexy, hypnagogic and hypnopompic hallucinations, sleep paralysis, and other symptoms Suvorexant promotes sleep by blocking orexin neuropeptides from binding to their receptors CLINICAL STUDIES — FDA approval of suvorexant was based on double-blind, placebo-controlled trials The Table Pharmacology Drug class Route Formulation Distribution Metabolism Tmax (fasting) Elimination Half-life Orexin receptor antagonist Oral 5, 10, 15, 20 mg tablets >99% protein bound Primarily by CYP3A4, and to a minor extent by CYP2C19 hours (range: 30 mins-6 hours) Feces (66%), urine (23%) ~12 hours first trials randomized 1260 patients with insomnia to suvorexant (20 mg for those 18-64 years old; 15 mg for those ≥65 years old) or placebo for months Compared to patients taking placebo, patients taking suvorexant fell asleep about 5-10 minutes sooner and stayed asleep about 15-25 minutes longer The effects of the drug on the first night were generally consistent with the effects at later time points.3 The third study was a crossover polysomnographic study in 249 patients 1864 years old with insomnia who received placebo for weeks and nightly suvorexant in doses ranging from 10 to 80 mg for another weeks Time to persistent sleep, compared to placebo, was 2.3 minutes shorter with 10 mg (not significant) and 22.3 minutes shorter with 20 mg (a significant difference) Total sleep time, compared to placebo, was 22.3 minutes longer with 10 mg and 49.9 minutes longer with 20 mg, both significant differences.4 In a one-year safety study that also measured drug efficacy as a secondary endpoint, 781 patients were randomized to nightly suvorexant in higher-thanapproved doses (40 mg for those 18-64 years old; 30 mg for those ≥65 years old) or to placebo At one year, patients on suvorexant fell asleep about 10 minutes faster and stayed asleep about 28 minutes longer than those on placebo After one year, patients on suvorexant either continued on the active drug or were switched to placebo for months Patients 29 Published by The Medical Letter, Inc • A Nonprofit Organization Revised 6/30/15: In the table below, the Pregnancy Category for flurazepam is “X” (not “C”) The Medical Letter March 2, 2015 Vol 57 (1463) ® Table Some Hypnotics Drug Onset of Action Duration Some Oral Formulations Hypnotic Dose Dose in Elderly Pregnancy Category* Cost1 30 intermediate 5, 10, 15, 20 mg tabs 10-20 mg 10-20 mg C $87.70 ultra-short 5, 10 mg caps 10-20 mg mg C 5.50 63.50 short 5, 10 mg tabs 5-10 mg2 mg C short 6.25, 12.5 mg ER tabs 6.25-12.5 mg2 6.25 mg C 0.90 120.00 47.50 120.00 short ultra-short 5, 10 mg tabs 1.75, 3.5 mg tabs 5-10 mg2 1.75-3.5 mg2 mg 1.75 mg C C 106.00 83.10 short intermediate mg/spray 1, 2, mg tabs 5-10 mg2 1-3 mg mg 1-2 mg C C 145.003 11.40 124.20 short 0.125, 0.25 mg tabs 0.25 mg tabs 1, mg tabs 7.5, 15, 22.5, 30 mg caps 0.125-0.25 mg 0.125-0.25 mg X 1-2 mg 15-30 mg 0.5-1 mg 7.5-15 mg X X 22.90 33.004 6.00 1.00 138.80 Orexin Receptor Antagonist Suvorexant – Belsomra (Merck) Benzodiazepine Receptor Agonists Zaleplon – generic 60% with either inhaled insulin or insulin aspart Tavaborole Topical Solution (Kerydin) for Onychomycosis 10 Tavaborole topical solution: a has been shown to be more effective than a placebo solution in treating toenail onychomycosis b has been shown to be more effective than ciclopirox in treating toenail onychomycosis c can cure onychomycosis in as little as weeks d all of the above ACPE UPN: Per Issue Exam: 0379-0000-15-463-H01-P; Release: March 2, 2015, Expire: March 2, 2016 Comprehensive Exam 72: 0379-0000-15-072-H01-P; Release: July 2015, Expire: July 2016 EDITOR IN CHIEF: Mark Abramowicz, M.D.; EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School; EDITOR: Jean-Marie Pflomm, Pharm.D.; ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.; CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D; SENIOR ASSOCIATE EDITOR: Amy Faucard CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons; Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School; Eric J Epstein, M.D., Albert Einstein College of Medicine; Jane P Gagliardi, M.D., M.H.S., F.A.C.P., Duke University School of Medicine; Jules Hirsch, M.D., Rockefeller University; David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre; Richard B Kim, M.D., University of Western Ontario; Hans Meinertz, M.D., University Hospital, Copenhagen; Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine; Dan M Roden, M.D., Vanderbilt University School of Medicine; Esperance A.K Schaefer, M.D., M.P.H., Harvard Medical School; F Estelle R Simons, M.D., University of Manitoba; Neal H Steigbigel, M.D., New York University School of Medicine; Arthur M F Yee, M.D., Ph.D., F.A.C.R., Weill Medical College of Cornell University MANAGING EDITOR: Susie Wong; ASSISTANT MANAGING EDITOR: Liz Donohue; EDITORIAL ASSISTANT: Cheryl Brown EXECUTIVE DIRECTOR OF SALES: Gene Carbona; FULFILLMENT & SYSTEMS MANAGER: Cristine Romatowski; DIRECTOR OF MARKETING COMMUNICATIONS: Joanne F Valentino; VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy Founded in 1959 by Arthur Kallet and Harold Aaron, M.D Copyright and Disclaimer: The Medical Letter, Inc is an independent nonprofit organization that provides healthcare professionals with unbiased drug prescribing recommendations The editorial process used for its publications relies on a review of published and unpublished literature, with an emphasis on controlled clinical trials, and on the opinions of its consultants The Medical Letter, Inc is supported solely by subscription fees and accepts no advertising, grants, or donations No part of the material may be reproduced or transmitted by any process in whole or in part without prior permission in writing The editors not warrant that all the material in this publication is accurate and complete in every respect The editors shall not be held responsible for any damage resulting from any error, inaccuracy, or omission Subscription Services Address: The Medical Letter, Inc 145 Huguenot St Ste 312 New Rochelle, NY 10801-7537 www.medicalletter.org Customer Service: Call: 800-211-2769 or 914-235-0500 Fax: 914-632-1733 E-mail: custserv@medicalletter.org Permissions: To reproduce any portion of this issue, please e-mail your request to: permissions@medicalletter.org Copyright 2015 ISSN 1523-2859 Subscriptions (US): year - $98; 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Published by The Medical Letter, Inc • A Nonprofit Organization Revised 6/30/15: In the table below, the Pregnancy Category for flurazepam is “X” (not “C”) The Medical Letter March 2, 20 15 Vol 57