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ZEPATIER Is Recommended

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ZEPATIER Is Recommended HIGHLIGHTS OF PRESCRIBING INFORMATION Renal Impairment, including hemodialysis: No dosage adjustment of These highlights do not include all the information needed to use ZEPATIER is recommended. Refer to ribavirin prescribing ZEPATIER safely and effectively. See full prescribing information information for ribavirin dosing and dosage modifications. (2.3) for ZEPATIER. --------------------- DOSAGE FORMS AND STRENGTHS --------------------- ZEPATIER® (elbasvir and grazoprevir) tablets, for oral use Tablets: 50 mg elbasvir and 100 mg grazoprevir (3) Initial U.S. Approval: 2016 -------------------------------CONTRAINDICATIONS------------------------------- Patients with moderate or severe hepatic impairment (Child-Pugh B WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN or C). (4) PATIENTS COINFECTED WITH HCV AND HBV OATP1B1/3 inhibitors that are known or expected to significantly See full prescribing information for complete boxed warning. increase grazoprevir plasma concentrations, strong CYP3A inducers, and efavirenz. (4) Hepatitis B virus (HBV) reactivation has been reported, in some If ZEPATIER is administered with ribavirin, the contraindications to cases resulting in fulminant hepatitis, hepatic failure, and death. ribavirin also apply. (4) (5.1) ----------------------- WARNINGS AND PRECAUTIONS ----------------------- ---------------------------RECENT MAJOR CHANGES --------------------------- Risk of Hepatitis B Virus Reactivation: Test all patients for evidence Dosage and Administration of current or prior HBV infection before initiation of HCV treatment. Hepatic Impairment (2.4) 12/2019 Monitor HCV/HBV coinfected patients for HBV reactivation and Contraindications (4) 12/2019 hepatitis flare during HCV treatment and post-treatment follow-up. Warnings and Precautions Initiate appropriate patient management for HBV infection as Risk of Hepatic Decompensation/Failure in Patients with Evidence clinically indicated. (5.1) of Advanced Liver Disease (5.3) 12/2019 ALT Elevations: Perform hepatic laboratory testing prior to therapy, ----------------------------INDICATIONS AND USAGE---------------------------- at treatment week 8, and as clinically indicated. For patients ZEPATIER is a fixed-dose combination product containing elbasvir, a receiving 16 weeks of therapy, perform additional hepatic laboratory hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV testing at treatment week 12. For ALT elevations on ZEPATIER, NS3/4A protease inhibitor, and is indicated for treatment of chronic follow recommendations in full prescribing information. (5.2) HCV genotype 1 or 4 infection in adults. ZEPATIER is indicated for use Risk of Hepatic Decompensation/Failure in Patients with Evidence of with ribavirin in certain patient populations. (1) Advanced Liver Disease: Hepatic decompensation/failure, including fatal outcomes, have been reported mostly in patients with cirrhosis ----------------------- DOSAGE AND ADMINISTRATION ----------------------- and baseline moderate or severe liver impairment (Child-Pugh B or Testing Prior to Initiation of Therapy: C) treated with HCV NS3/4A protease inhibitor-containing regimens. Test all patients for HBV infection by measuring HBsAg and anti- Monitor for clinical and laboratory evidence of hepatic HBc. (2.1) decompensation. Discontinue ZEPATIER in patients who develop Genotype 1a: Testing for the presence of virus with NS5A evidence of hepatic decompensation/failure. (5.3) resistance-associated polymorphisms is recommended. (2.1) Risk Associated with Ribavirin Combination Treatment: If ZEPATIER Obtain hepatic laboratory testing. (2.1) is administered with ribavirin, the warnings and precautions for Recommended dosage: One tablet taken orally once daily with or ribavirin also apply. (5.4) without food. (2.2) ------------------------------ ADVERSE REACTIONS ------------------------------ Dosage Regimens and Durations for ZEPATIER in Patients with In subjects receiving ZEPATIER for 12 weeks, the most commonly Genotype 1 or 4 HCV with or without Cirrhosis reported adverse reactions of all intensity (greater than or equal to 5% Patient Population Treatment Duration in placebo-controlled trials) were fatigue, headache, and nausea. In subjects receiving ZEPATIER with ribavirin for 16 weeks, the most Genotype 1a: commonly reported adverse reactions of moderate or severe intensity Treatment-naïve or PegIFN/RBV- (greater than or equal to 5%) were anemia and headache. (6.1) experienced* without baseline † NS5A polymorphisms ZEPATIER 12 weeks To report SUSPECTED ADVERSE REACTIONS, contact Merck Genotype 1a: Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877- Treatment-naïve or PegIFN/RBV- 888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. experienced* with baseline NS5A ZEPATIER + polymorphisms† ribavirin 16 weeks -------------------------------DRUG INTERACTIONS------------------------------- Genotype 1b: Co-administration of ZEPATIER with moderate CYP3A inducers is Treatment-naïve or PegIFN/RBV- not recommended as they may decrease the plasma concentration experienced* ZEPATIER 12 weeks of ZEPATIER. (7) Genotype 1a or 1b: ZEPATIER + Co-administration of ZEPATIER with certain strong CYP3A inhibitors PegIFN/RBV/PI-experienced‡ ribavirin 12 weeks is not recommended as they may increase the plasma concentration Genotype 4: of ZEPATIER. (7) Treatment-naïve ZEPATIER 12 weeks Clearance of HCV infection with direct-acting antivirals may lead to Genotype 4: ZEPATIER + changes in hepatic function, which may impact safe and effective PegIFN/RBV-experienced* ribavirin 16 weeks use of concomitant medications. Frequent monitoring of relevant *Peginterferon alfa + ribavirin. laboratory parameters (INR or blood glucose) and dose adjustments †Polymorphisms at amino acid positions 28, 30, 31, or 93. of certain concomitant medications may be necessary. (7.2) ‡Peginterferon alfa + ribavirin + HCV NS3/4A protease inhibitor. Consult the full prescribing information prior to and during treatment for potential drug interactions. (4, 5.5, 7, 12.3) HCV/HIV-1 co-infection: Follow the dosage recommendations in the See 17 for PATIENT COUNSELING INFORMATION and FDA- table above. (2.2) approved patient labeling. Revised: 12/2019 FULL PRESCRIBING INFORMATION: CONTENTS* 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN 8.5 Geriatric Use PATIENTS COINFECTED WITH HCV AND HBV 8.6 Gender 1 INDICATIONS AND USAGE 8.7 Race 2 DOSAGE AND ADMINISTRATION 8.8 Renal Impairment 2.1 Testing Prior to the Initiation of Therapy 8.9 Hepatic Impairment 2.2 Recommended Dosage in Adults 10 OVERDOSAGE 2.3 Renal Impairment 11 DESCRIPTION 2.4 Hepatic Impairment 12 CLINICAL PHARMACOLOGY 3 DOSAGE FORMS AND STRENGTHS 12.1 Mechanism of Action 4 CONTRAINDICATIONS 12.2 Pharmacodynamics 5 WARNINGS AND PRECAUTIONS 12.3 Pharmacokinetics 5.1 Risk of Hepatitis B Virus Reactivation in Patients Coinfected 12.4 Microbiology with HCV and HBV 13 NONCLINICAL TOXICOLOGY 5.2 Increased Risk of ALT Elevations 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.3 Risk of Hepatic Decompensation/Failure in Patients with 14 CLINICAL STUDIES Evidence of Advanced Liver Disease 14.1 Overview of Clinical Trials 5.4 Risks Associated with Ribavirin Combination Treatment 14.2 Clinical Trials in Treatment-Naïve Subjects with Genotype 1 5.5 Risk of Adverse Reactions or Reduced Therapeutic Effect HCV (C-EDGE TN and C-EDGE COINFECTION) Due to Drug Interactions 14.3 Clinical Trials in Treatment-Experienced Subjects with 6 ADVERSE REACTIONS Genotype 1 HCV 6.1 Clinical Trials Experience 14.4 Clinical Trial in Subjects with Genotype 1 HCV and Severe 6.2 Postmarketing Experience Renal Impairment including Subjects on Hemodialysis (C- 7 DRUG INTERACTIONS SURFER) 7.1 Potential for Drug Interactions 14.5 Clinical Trials with Genotype 4 HCV 7.2 Established and other Potentially Significant Drug 16 HOW SUPPLIED/STORAGE AND HANDLING Interactions 17 PATIENT COUNSELING INFORMATION 7.3 Drugs without Clinically Significant Interactions with ZEPATIER *Sections or subsections omitted from the full prescribing information 8 USE IN SPECIFIC POPULATIONS are not listed. 8.1 Pregnancy 8.2 Lactation FULL PRESCRIBING INFORMATION WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ZEPATIER. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated [see Warnings and Precautions (5.1)]. 1 INDICATIONS AND USAGE ZEPATIER® is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin in certain patient populations [see Dosage and Administration (2.2)]. 2 DOSAGE AND ADMINISTRATION 2.1 Testing Prior to the Initiation of Therapy Testing for HBV Infection Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with ZEPATIER [see
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