Zepatier for Hep C: What Pharmacists Should Know

AUGUST 14, 2016
Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease in the United States. The CDC even estimates between 2.7 and 3.9 million US individuals are infected with chronic HCV.
Fortunately, a number of direct-acting antivirals (DAAs) have been approved to treat HCV. Early this year, the FDA approved Zepatier, a fixed-dose combination of elbasvir and grazoprevir, to treat chronic HCV genotypes 1 or 4 with or without ribavirin in adults.

Mechanism of Action
Zepatier is a combination of 2 DAAs with distinct mechanisms of action and nonoverlapping resistance profiles to target HCV at multiple steps in the viral lifecycle.

Elbasvir is an inhibitor of HCV NS5A, which is essential for viral RNA replication and virion assembly. Grazoprevir is an inhibitor of the HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein and essential for viral replication.

Formulation and Storage
Each Zepatier tablet contains 50 mg elbasvir and 100 mg grazoprevir. The tablets are packaged in a carton containing 2 14-count, child-resistant dose packs for a total of 28 tablets.

Zepatier should be stored in the original blister package until use to protect from moisture.

Zepatier is administered as 1 tablet taken orally once-daily with or without food. Patients with HCV genotype 1a should be tested for the presence of virus with NS5A resistance-associated polymorphisms.
Here are recommended dosage regimens and durations for Zepatier in patients with HCV genotype 1 or 4 with or without cirrhosis:
Population Treatment Duration
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-experienced Zepatier + RBV 12 weeks
Genotype 4: Treatment-naïve Zepatier 12 weeks
Genotype 4: PegIFN/RBV-experienced Zepatier + RBV 16 weeks
RBV = ribavirin; PegIFN = peginterferon alfa

Timothy O'Shea, PharmD
Timothy O'Shea, PharmD
Timothy O'Shea, PharmD, is a Clinical Pharmacist working at a large health insurance plan on the east coast. Additionally he works per diem at a retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.