Zepatier for Hep C: What Pharmacists Should Know


This fixed-dose combination of elbasvir and grazoprevir is indicated to treat chronic HCV genotypes 1 or 4 with or without ribavirin in adults.

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:




Genotype 1a: Treatment-naïve or PegIFN/RBV-experienced without baseline NS5A polymorphisms


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


12 weeks

Genotype 1a or 1b: PegIFN/RBV-experienced

Zepatier + RBV

12 weeks

Genotype 4: Treatment-naïve


12 weeks

Genotype 4: PegIFN/RBV-experienced

Zepatier + RBV

16 weeks

RBV = ribavirin; PegIFN = peginterferon alfa


This was established in 6 clinical trials with a total of more than 1400 treatment-naïve and treatment-experienced patients with HCV genotype 1, 4, or 6. All subjects had compensated liver disease with or without cirrhosis. Sustained virologic response, defined as HCV RNA less than the lower limit of quantification at 12 weeks following treatment, ranged from 92% to 97%.

In genotype 1a-infected subjects, the presence of 1 or more HCV NS5A amino acid polymorphisms at specific positions was associated with reduced efficacy of Zepatier, regardless of prior treatment history or cirrhosis status. The prevalence of these polymorphisms in genotype 1a-infected subjects was 11% (62/561) overall.


The most common adverse reactions are fatigue, headache, and nausea. In subjects receiving Zepatier with ribavirin, the most commonly reported adverse reactions of moderate or severe intensity were anemia and headache.

Zepatier is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) and those taking concurrent OATP1B1/3 inhibitors, strong CYP3A inducers, and efavirenz.

Drug Interactions

Grazoprevir is a substrate of OATP1B1/3 transporters. Co-administration of Zepatier with drugs that inhibit OATP1B1/3 transporters may result in a significant increase in the plasma concentrations of grazoprevir and are therefore contraindicated. Co-administration with strong CYP3A inhibitors may increase elbasvir and grazoprevir concentrations and therefore concurrent use is contraindicated.

The following drugs are a direct contraindication with Zepatier: phenytoin, carbamazepine, rifampin, St. John’s Wort, efavirenz, atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine.

Co-administration of Zepatier with nafcillin, ketoconazole, bosentan, tacrolimus, Stribild, atorvastatin (>20 mg), or modafinil isn’t generally recommended.

Product Comparison

Indicated HCV Genotype(s)


AWP (28 days)



1, 4

QD x 12-16 weeks




1, 4, 5, 6

QD x 12-24 weeks


Viekira Pak

(ombitasvir/paritaprevir/ ritonavir and dasabuvir)


BID x 12-24 weeks




1, 2, 3, 4, 5, 6

QD x 12-24 weeks


Daklinza (daclatasvir) + Sovaldi (sofosbuvir)

1, 3

QD x 12-24 weeks



(ombitasvir/paritaprevir/ ritonavir)


QD x 12 weeks


Cost will vary based on individual insurance coverage.


The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend Zepatier as a first-line option in treatment-naïve and treatment-experienced patients with HCV genotypes 1 and 4. However, no treatment preferences are made among all of the different DAAs.


Zepatier is considered highly effective in treating HCV genotypes 1 and 4, and also well-tolerated. It may be more affordable than other medications for HCV.

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