The medical letter on drugs and therapeutics january 6 2014

Simeprevir (Olysio) for Chronic Hepatitis C The FDA has recently approved 2 new drugs for treatment of chronic hepatitis C virus (HCV) infection. Simeprevir (Olysio – Janssen) is the third oral protease inhibitor to... New Oral Anticoagulants for Acute Venous Thromboembolism Anticoagulants are the drugs of choice for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively referred to as venous thromboembolism (VTE). In Brief: Khedezla - A New Brand of Desvenlafaxine The FDA has approved the marketing of another extended-release brand-name formulation of the serotonin and norepinephrine reuptake inhibitor (SNRI) desvenlafaxine (Khedezla – Par/Osmotica) for...

The Medical Letter ® On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Simeprevir (Olysio) for Chronic Hepatitis C .p New Oral Anticoagulants for Acute Venous Thromboembolism p In Brief: Khedezla — A New Brand of Desvenlafaxine p Important Copyright Message The Medical Letter® publications are protected by US 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 US 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 FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS 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 Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 56 (Issue 1433) January 6, 2014 Take CME exams ALSO IN THIS ISSUE New Oral Anticoagulants for Acute Venous Thromboembolism p In Brief: Khedezla — A New Brand of Desvenlafaxine .p 2013 Year-End Index For an electronic copy of the 2013 index, go to: www.medicalletter.org/downloads/tmlindex2013.pdf Simeprevir (Olysio) for Chronic Hepatitis C The FDA has recently approved new drugs for treatment of chronic hepatitis C virus (HCV) infection Simeprevir (Olysio – Janssen) is the third oral protease inhibitor to be approved for use in combination with peginterferon and ribavirin for treatment of chronic HCV genotype infection in adults with compensated liver disease Telaprevir (Incivek) and boceprevir (Victrelis) were approved in 2011 for the same indication Sofosbuvir (Sovaldi – Gilead), a nucleotide analog polymerase inhibitor that has been approved for use with and without interferon for treatment of multiple HCV genotypes, will be reviewed in the next issue of The Medical Letter Table Pharmacology Class NS3/4A protease inhibitor Route Oral Formulation 150 mg capsules Tmax 4-6 hours Distribution >99.9% protein bound Metabolism Excretion Half-life Hepatic, primarily CYP3A Feces (91%) 41 hours STANDARD THERAPY — For many years, the standard therapy for chronic HCV genotype infection (the most common genotype in the US and Europe) was 48 weeks of subcutaneously-injected pegylated interferon alfa and oral ribavirin This combination usually www.medicalletter.org Table Protease Inhibitors for Chronic Hepatitis C Genotype Infection Drug Usual Adult Dosage Telaprevir – Incivek (Vertex)2 750 mg tid PO x 12 wks3 Boceprevir – Victrelis (Merck)4 800 mg tid PO x 24-44 wks3 36,506.205 Simeprevir – Olysio (Janssen)6 150 mg once/day PO x 12 wks3 66,360.00 Cost1 $66,155.10 Approximate wholesale acquisition cost (WAC) for 12 weeks’ treatment Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) December 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Cost of peginterferon and ribavirin is not included Available as a 375-mg tablet Must be taken with food (not low fat) Given in combination with peginterferon and ribavirin (PR) PR treatment duration should be based on patient response with boceprevir (28, 36, or 48 weeks [includes weeks of peginterferon and ribavirin before starting boceprevir]) and telaprevir (24 or 48 weeks); treatment duration with simeprevir is 24 or 48 weeks depending on baseline characteristics of patients Available as a 200-mg capsule Must be taken with a light meal or snack Cost for 24 weeks of treatment Available as a 150-mg capsule Must be taken with food produces a sustained virologic response (SVR; undetectable HCV RNA 24 weeks after stopping treatment) in 40-50% of patients with HCV genotype infection Addition of telaprevir or boceprevir to peginterferon and ribavirin increases SVR rates to 60-75% and has become the standard of care for patients with HCV genotype infection.1-3 CLINICAL STUDIES — The efficacy of simeprevir was evaluated in three phase (QUEST and 2, PROMISE) and two phase 2b (PILLAR, ASPIRE) randomized, double-blind, placebo-controlled trials in more than 2000 treatment-naïve and treatment-experienced patients with chronic HCV genotype infection Patients taking simeprevir with peginterferon/ribavirin had significantly higher SVR rates compared to placebo in all of the trials (Table 3) The efficacy of simeprevir was substantially reduced in patients with HCV genotype 1a infection who had the NS3 Q80K polymorphism at baseline (35% of US patients in the clinical studies) Genotype 1a patients should be screened for this polymorphism and alterna- FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS tive therapy should be considered for those who have it Efficacy was not reduced in patients with the Q80K polymorphism who received telaprevir or boceprevir in clinical trials In general, however, patients who fail treatment with simeprevir may also be resistant to treatment with the other approved protease inhibitors No controlled clinical trials are available comparing simeprevir with either telaprevir or boceprevir Table Simeprevir Clinical Studies SVR Rates (simeprevir vs placebo) Clinical Trial Treatment-Naïve Patients QUEST and QUEST (n=785)1,2 Simeprevir 150 mg x 12 wks + PR x 24 or 48 wks3 Placebo + PR 48 wks PILLAR (n=386)4 Simeprevir 75 or 150 mg x 12 or 24 wks + PR x 24 or 48 wks3 Placebo x 24 wks + PR x 48 wks SVR12: 80% vs 50% SVR24: 75-86% vs 65% Treatment-Experienced Patients PROMISE (n=393)5 Simeprevir 150 mg x 12 wks + PR x 24 or 48 wks3 Placebo + PR x 48 wks SVR12: 80% vs 37% ASPIRE (n=462)6 Simeprevir 100 or 150 mg x 12, 24, or 48 wks + PR x 48 wks Placebo + PR x 48 wks SVR24: 61-80% vs 23% PR = peginterferon plus ribavirin; SVR12 = HCV RNA 75 years old, had a creatinine clearance (CrCl) 5 days, the parenteral anticoagulant is stopped and warfarin is continued as monotherapy, usually for at least months.1 NEW ORAL ANTICOAGULANTS — Rivaroxaban (Xarelto), dabigatran etexilate (Pradaxa), apixaban (Eliquis), and edoxaban (not FDA-approved) have all been studied for treatment of acute VTE, but only rivaroxaban is FDA-approved for this indication Unlike warfarin, the newer drugs not require INR monitoring and have no dietary restrictions, but they have shorter half-lives (increasing the risks associated with missed doses) and no specific antidote to reverse their anticoagulant effect Table Oral Anticoagulants for Treatment of Venous Thromboembolism Drug Mechanism of Action Warfarin – generic (Coumadin) Rivaroxaban – (Xarelto) Vitamin K antagonist Direct factor Xa inhibitor Apixaban – (Eliquis)4 Direct factor Xa inhibitor Dabigatran etexilate – Direct thrombin (Pradaxa)4 inhibitor Usual Dosage Cost1 2-10 mg $6.00 once/d 43.00 15 mg bid for wks, 265.00 then 20 mg once/d3 10 mg bid for days, 265.00 then mg bid5 150 mg bid6 265.00 Approximate wholesale acquisition cost of 30 days’ treatment at the lowest daily dose Source: Analy$ource® Monthly (Selected from FDB Medknowledge™) December 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Monitor INR daily and adjust dose until in therapeutic range (2-3) for >24 hours With food; avoid use with combined P-glycoprotein and strong CYP3A4 inhibitors or inducers, or in patients with CrCl