Elbasvir and Grazoprevir

ZEPATIER ® is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adult and pediatric patients 12 years of age and older or weighing at least 30 kg. ZEPATIER is indicated for use with ribavirin in certain patient populations. ZEPATIER is a fixed-dose combination product containing elbasvir, a hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated for treatment of chronic HCV genotype 1 or 4 infection in adult and pediatric patients 12 years of age and older or weighing at least 30 kg.

ZEPATIER is a fixed-dose combination of elbasvir and grazoprevir which are direct-acting antiviral agents against the hepatitis C virus.

Testing Prior to Initiation of Therapy: Test all patients for HBV infection by measuring HBsAg and anti-HBc. Genotype 1a: Testing for the presence of virus with NS5A resistance-associated polymorphisms is recommended. Obtain hepatic laboratory testing. Recommended dosage in adult and pediatric patients 12 years of age and older or weighing at least 30 kg: One tablet taken orally once daily with or without food. Dosage Regimens and Durations for ZEPATIER in Patients with Genotype 1 or 4 HCV with or without Cirrhosis Patient Population Treatment Duration Genotype 1a: Treatment-naïve or PegIFN/RBV-experienced Peginterferon alfa + ribavirin. without baseline NS5A polymorphisms Polymorphisms at amino acid positions 28, 30, 31, or 93.

ZEPATIER is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) due to the expected significantly increased grazoprevir plasma concentration and the increased risk of alanine aminotransferase (ALT) elevations. ZEPATIER is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of hepatic decompensation due to the risk of hepatic decompensation.

Boxed warning: 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. Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. Monitor HCV/HBV coinfected patients for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. ALT Elevations: Perform hepatic laboratory testing prior to therapy, at treatment week 8, and as clinically indicated.

The following adverse reaction is described below and elsewhere in the labeling: Increased Risk of ALT Elevations. In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache, and nausea. In subjects receiving ZEPATIER with ribavirin for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.

Co-administration of ZEPATIER with moderate CYP3A inducers is not recommended as they may decrease the plasma concentration of ZEPATIER. Co-administration of ZEPATIER with certain strong CYP3A inhibitors is not recommended as they may increase the plasma concentration of ZEPATIER. Clearance of HCV infection with direct-acting antivirals may lead to changes in hepatic function, which may impact safe and effective use of concomitant medications. Frequent monitoring of relevant laboratory parameters (INR or blood glucose) and dose adjustments of certain concomitant medications may be necessary. Consult the full prescribing information prior to and during treatment for potential drug interactions.

Store ZEPATIER at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (between 59°F to 86°F). Store ZEPATIER in the original blister package until use to protect from moisture.