ZEPATIER

ZEPATIER- elbasvir and grazoprevir anhydrous tablet, film coated
Merck Sharp & Dohme LLC

1 INDICATIONS AND USAGE

​ 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 [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 Warnings and Precautions (5.1)].

NS5A Resistance Testing in HCV Genotype 1a-Infected Patients

Testing patients with HCV genotype 1a infection for the presence of virus with NS5A resistance-associated polymorphisms is recommended prior to initiation of treatment with ZEPATIER to determine dosage regimen and duration [see Dosage and Administration (2.2), Table 1]. In subjects receiving ZEPATIER for 12 weeks, sustained virologic response (SVR12) rates were lower in genotype 1a-infected patients with one or more baseline NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93 [see Microbiology (12.4), Table 12].

Hepatic Laboratory Testing

Obtain hepatic laboratory testing prior to and during treatment with ZEPATIER [see Warnings and Precautions (5.2, 5.3)].

​ 2.2 Recommended Dosage in Adult and Pediatric Patients 12 Years of Age and Older or Weighing at Least 30 kg

​ ZEPATIER is a two-drug, fixed-dose combination product containing 50 mg of elbasvir and 100 mg of grazoprevir in a single tablet. The recommended dosage of ZEPATIER is one tablet taken orally once daily with or without food [see Clinical Pharmacology (12.3)]. ZEPATIER is used in combination with ribavirin in certain patient populations (see Table 1). When administered with ZEPATIER, the recommended dosage of ribavirin in patients without renal impairment is weight-based administered in two divided doses with food. For further information on ribavirin dosing and dosage modifications, refer to the ribavirin prescribing information.

Treatment Regimen and Duration of Therapy

Relapse rates are affected by baseline host and viral factors and differ between treatment regimens and durations for certain subgroups [see Clinical Studies (14)].

Table 1 below provides the recommended ZEPATIER treatment regimen and duration based on the patient population and genotype in HCV mono-infected and HCV/HIV-1 co-infected patients with or without cirrhosis and with or without renal impairment including patients receiving hemodialysis.

Table 1: Recommended Dosage Regimens and Durations for ZEPATIER for Treatment of HCV Genotype 1 or 4 in Patients with or without Cirrhosis

Patient Population	Treatment	Duration
* Patients who have failed treatment with peginterferon alfa (PegIFN) + ribavirin (RBV). † NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93. See section 2.1 Testing prior to the initiation of therapy, subsection NS5A resistance testing in HCV genotype 1a-infected patients. ‡ For patients with CrCl greater than 50 mL per minute, the recommended dosage of ribavirin is weight-based (less than 66 kg = 800 mg per day, 66 to 80 kg = 1000 mg per day, 81 to 105 kg = 1200 mg per day, greater than 105 kg = 1400 mg per day) administered in two divided doses with food. For patients with CrCl less than or equal to 50 mL per minute, including patients receiving hemodialysis, refer to the ribavirin tablet prescribing information for the correct ribavirin dosage.In pediatric patients, the dosing for ribavirin is weight-based in two divided doses. Refer to the ribavirin tablet prescribing information for the correct ribavirin dosage regimen. § The optimal ZEPATIER-based treatment regimen and duration of therapy for PegIFN/RBV/PI-experienced genotype 1a-infected patients with one or more baseline NS5A resistance-associated polymorphisms at positions 28, 30, 31, and 93 has not been established. ¶ Patients who have failed treatment with PegIFN + RBV + HCV NS3/4A protease inhibitor (PI): boceprevir, simeprevir, or telaprevir.
Genotype 1a: Treatment-naïve or PegIFN/RBV-experienced *without baseline NS5A polymorphisms †	ZEPATIER	12 weeks
Genotype 1a: Treatment-naïve or PegIFN/RBV-experienced *with baseline NS5A polymorphisms †	ZEPATIER + RBV ‡	16 weeks
Genotype 1b: Treatment-naïve or PegIFN/RBV-experienced *	ZEPATIER	12 weeks
Genotype 1a § or 1b: PegIFN/RBV/PI-experienced ¶	ZEPATIER + RBV ‡	12 weeks
Genotype 4: Treatment-Naïve	ZEPATIER	12 weeks
Genotype 4: PegIFN/RBV-experienced *	ZEPATIER + RBV ‡	16 weeks

2.3 Renal Impairment

No dosage adjustment of ZEPATIER is recommended in patients with any degree of renal impairment including patients on hemodialysis. Administer ZEPATIER with or without ribavirin according to the recommendations in Table 1 [see Use in Specific Populations (8.8) and Clinical Studies (14.4)]. Refer to the ribavirin tablet prescribing information for the correct ribavirin dosage for patients with CrCl less than or equal to 50 mL per minute.