The medical letter on drugs and therapeutics janurary 2 2017

Antiviral Drugs for Seasonal Influenza 2016-2017 Antiviral drugs can be used for prophylaxis and treatment of influenza. Frequently updated information on influenza activity, testing for influenza, and antiviral resistance is available from the... Another Insulin Glargine (Basaglar) for Diabetes The FDA has approved Basaglar (Lilly/Boehringer Ingelheim), a "follow-on" 100 units/mL insulin glargine product similar to Lantus (Sanofi), which recently went off patent. A 300... Ustekinumab (Stelara) for Crohn''s Disease The FDA has approved the human interleukin (IL)-12 and -23 antagonist ustekinumab (Stelara – Janssen Biotech) for treatment of moderately to severely active Crohn''s disease in adults who... Tenofovir Alafenamide (Vemlidy) for Hepatitis B The FDA has approved tenofovir alafenamide (Vemlidy – Gilead) for treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease. It is the first...

The Medical Letter ® on Drugs and Therapeutics Volume 59 ISSUE ISSUE No 1433 1511 Volume 56 January 2, 2017 IN THIS ISSUE Antiviral Drugs for Seasonal Influenza 2016-2017 p Another Insulin Glargine (Basaglar) for Diabetes p Ustekinumab (Stelara) for Crohn’s Disease p Tenofovir Alafenamide (Vemlidy) for Hepatitis B p 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 Volume 59 January 2, 2017 Take CME Exams ISSUE ISSUE No 1433 1511 Volume 56 ALSO IN THIS ISSUE Another Insulin Glargine (Basaglar) for Diabetes p Ustekinumab (Stelara) for Crohn’s Disease p Tenofovir Alafenamide (Vemlidy) for Hepatitis B p We asked you what topics you wanted to see more of in The Medical Letter, and you told us So as this new year begins, you will soon see, in addition to our traditional coverage, more articles reviewing all of the drugs used to treat common conditions such as diabetes, hypertension, migraine, and asthma appearing in our issues on a regular basis With so much to cover, you may also see our issues increase in length and more articles published only online Remember to visit our website or mobile app regularly for additional content and to earn free CME credits and ABIM MOC points Happy New Year! ▶ Antiviral Drugs for Seasonal Influenza 2016-2017 Antiviral drugs can be used for prophylaxis and treatment of influenza Frequently updated information on influenza activity, testing for influenza, and antiviral resistance is available from the CDC at www.cdc.gov/flu INDICATIONS FOR TREATMENT — The CDC recommends starting antiviral treatment as soon as possible after illness onset, without waiting for the results of influenza testing Antiviral treatment is indicated for all persons with suspected or confirmed influenza who are at high risk for complications, including children 10-30 mL/min: 30 mg once daily HD: 30 mg after every HD CAPD: 30 mg after exchange ESRD not on HD: not recommended No dosage adjustment required for renal impairment CrCl 30-49 mL/min: 200 mg once CrCl 10-29 mL/min: 100 mg once HD: administer dose (based on CrCl) after HD ≥7 yrs: inhalations bid x days Not FDA-approved for use in children Pediatric Dosage 30-75 mg7 PO bid x days8 CAPD = continuous ambulatory peritoneal dialysis; ESRD = end-stage renal disease; HD = hemodialysis Inhaled zanamivir is not recommended for use in patients with underlying respiratory disease such as asthma or COPD or in patients with severe influenza, including hospitalized patients Contraindicated in patients with a history of allergy to milk protein Available in a carton containing rotadisks (each rotadisk contains four 5-mg blisters of the active drug in a lactose carrier) and a Diskhaler inhalation device Zanamivir should not be used in a nebulizer Approximate WAC for days’ treatment with oseltamivir or zanamivir, or a single dose of peramivir at the adult dosage WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly December 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy Cost at www.healthwarehouse.com Accessed December 20, 2016 After the last known exposure For prophylaxis of exposures in institutions, the drug should be taken for at least weeks and continued for week after the end of the outbreak For prophylaxis during community outbreaks, oseltamivir has been shown to be effective and safe when taken for up to 42 days, and zanamivir for up to 28 days Some expert clinicians would use twice-daily therapeutic doses for post-exposure prophylaxis in highly immunocompromised persons Initial dose can be administered before start of HD Dose for children 1-12 yrs old: ≤15 kg: 30 mg; 15.1-23 kg: 45 mg; 23.1-40 kg: 60 mg; ≥40.1 kg: 75 mg The FDA-approved dosage for treatment of infants ≥2 weeks to 55-85 kg: 390 mg; >85 kg: 520 mg Cost based on a 75-kg patient Infliximab-dyyb (Inflectra) is a Remicade biosimilar PREGNANCY AND LACTATION — There are no adequate studies of ustekinumab use in pregnant women No teratogenic or other adverse developmental effects were observed in the fetuses of pregnant monkeys who were given high doses of ustekinumab In one study in which 40 pregnant monkeys were given high doses of ustekinumab and 20 were given placebo, there were neonatal deaths in the ustekinumab group and no deaths in the placebo group Ustekinumab has been detected in the milk of lactating monkeys DRUG INTERACTIONS — Patients should not receive live vaccines during treatment with ustekinumab Proinflammatory cytokines can alter the formation of CYP enzymes Starting treatment with ustekinumab may normalize CYP enzyme formation and could alter the metabolism of CYP substrates; dosage adjustment of substrates with narrow therapeutic indices such as warfarin or cyclosporine may be needed Ustekinumab may decrease the protective effect of allergen immunotherapy DOSAGE AND ADMINISTRATION — The recommended induction dosage of ustekinumab for treatment of Crohn’s disease is 260 mg in patients who weigh ≤55 kg, 390 mg in those >55-85 kg, and 520 mg in those >85 kg The induction dose should be administered as a single IV infusion over at least January 2, 2017 one hour The recommended maintenance dosage is 90 mg injected subcutaneously every weeks Stelara is available for IV infusion in single-dose vials containing 130 mg/26 mL It is also available for SC injection in single-dose prefilled syringes containing 90 mg/mL and single-dose vials and prefilled syringes containing 45 mg/0.5 mL Patients may use the syringes to self-inject after receiving proper training CONCLUSION — Ustekinumab (Stelara), an interleukin (IL)-12 and -23 antagonist, is effective for treatment of moderately to severely active Crohn’s disease in adults who have had an inadequate response to or could not tolerate standard therapies, including tumor necrosis factor (TNF) inhibitors How it compares to the other biologic agents for treatment of Crohn’s disease remains to be determined ■ Drugs for psoriasis Med Lett Drugs Ther 2015; 57:81 Drugs for psoriatic arthritis Med Lett Drugs Ther 2015; 57:e88 Drugs for inflammatory bowel disease Med Lett Drugs Ther 2014; 56:65 Vedolizumab (Entyvio) for inflammatory bowel disease Med Lett Drugs Ther 2014; 56:86 W Strober et al Proinflammatory cytokines underlying the inflammation of Crohn’s disease Curr Opin Gastroenterol 2010; 26:310 B Feagan et al Ustekinumab as induction and maintenance therapy for Crohn’s disease N Engl J Med 2016; 375:1946 KA Papp et al Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from years of follow-up Br J Dermatol 2013; 168:844 ▶ Tenofovir Alafenamide (Vemlidy) for Hepatitis B The FDA has approved tenofovir alafenamide (Vemlidy – Gilead) for treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease It is the first single-drug product containing tenofovir alafenamide (TAF), a prodrug of the nucleotide reverse transcriptase inhibitor tenofovir, to become available; several combination products containing TAF are approved for treatment of HIV-1 infection Tenofovir disoproxil fumarate (TDF; Viread – Gilead), another tenofovir prodrug, has been used for many years for treatment of chronic HBV infection; a generic formulation of TDF is expected to become available in December 2017 Pronunciation Key Tenofovir alafenamide: ten of' oh veer al" a fen' a mide Vemlidy: vem li' dee The Medical Letter Vol 59 (1511) ® STANDARD TREATMENT — The goal of chronic HBV treatment is to reduce the risk of cirrhosis, hepatic failure, and hepatocellular carcinoma Effective therapy can reduce the viral load and promote HBV e-antigen seroconversion (loss of HBeAg with development of HBe antibodies); loss of HBV surface antigen (HBsAg) is uncommon Peginterferon alfa-2a (PEG-IFN; Pegasys), entecavir (Baraclude, and generics), and tenofovir are considered preferred options for initial treatment of chronic HBV infection in treatment-naive adults PEGIFN is injected once weekly for 48 weeks, but it can cause intolerable adverse effects, has many contraindications, and is expensive Entecavir and tenofovir have lower rates of resistance than other nucleoside/tide analogs and are more likely to induce virologic suppression These drugs may need to be taken indefinitely.1-3 TAF vs TDF — Systemic exposure to tenofovir may cause nephrotoxicity and reduce bone mineral density (BMD).4 TAF is delivered efficiently to hepatocytes,5 and unlike TDF, which is extensively converted to tenofovir in plasma, TAF activation predominantly occurs intracellularly In a pharmacokinetic analysis, TAF 25 mg once daily produced circulating tenofovir levels that were 86% lower and intracellular tenofovir levels that were times higher than those achieved with TDF 300 mg once daily.6 CLINICAL STUDIES — Approval of TAF for treatment of chronic HBV infection was based on the results of two double-blind noninferiority trials, one in 425 patients with HBeAg-negative infection and the other in 873 patients with HBeAg-positive infection In both trials, patients were randomized to receive once-daily treatment with TAF 25 mg or TDF 300 mg The primary endpoint was the rate of virologic suppression (HBV DNA 190 mg/dL (4% vs 190 mg/dL d all of the above 10 The patient in the previous question has a CrCl of 65 mL/min and also takes carbamazepine for bipolar disorder Which of the following statements about the use of TAF in this patient is correct? a concurrent use of TAF and carbamazepine is contraindicated b he should take 25 mg of TAF once daily c he should take 50 mg of TAF once daily because he also takes carbamazepine d he should take 12.5 mg of TAF once daily because of his renal function ACPE UPN: Per Issue Exam: 0379-0000-17-511-H01-P; Release: January 2, 2017 Expire: January 2, 2018 Comprehensive Exam 76: 0379-0000-17-076-H01-P; Release: July 2017, Expire: July 2018 PRESIDENT: Mark Abramowicz, M.D.; VICE PRESIDENT AND EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School; EDITOR IN CHIEF: Jean-Marie Pflomm, Pharm.D.; ASSOCIATE EDITORS: Susan M Daron, Pharm.D., Amy Faucard, MLS, Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.; CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D 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; David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre; Richard B Kim, M.D., University of Western Ontario; Franco M Muggia, M.D., New York University Medical Center; 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 FULFILLMENT AND SYSTEMS MANAGER: Cristine Romatowski; SITE LICENSE SALES: Gene Carbona, Elaine Reaney-Tomaselli; EXECUTIVE DIRECTOR OF MARKETING AND 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 does not sell advertising or receive any commercial support 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 Get Connected: 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 2017 ISSN 1523-2859 Subscriptions (US): year - $159; 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