elbasvir and grazoprevir

Zepatier is an oral tablet containing two drugs used for the treatment of chronic infection with the hepatitis C virus (HCV), genotype 1 and 4 in adults. The components belong to a class of drugs called direct-acting antiviral agents. Similar drugs include:

• boceprevir (Victrelis)
• sofosbuvir (Sovaldi)
• simeprevir (Olysio)
• telaprevir (Incivek),
• Viekira Pak (ombitasvir, paritaprevir, ritonavir, dasabuvir)
• ledipasvir and sofosbuvir (Harvoni)

Zepatier contains elbasvir and grazoprevir. Elbasvir directly blocks replication of HCV by interfering with a hepatitis C virus enzyme called NS5A. Grazoprevir is an inhibitor of another hepatitis C virus enzyme called NS3/4A, which also is needed for viral replication. Both drugs in Zepatier interfere with enzymes needed by hepatitis C virus to multiply and make new viruses, thus reducing the overall viral load. The efficacy of Zepatier has been established in subjects with hepatitis C virus genotypes 1 and 4.

Zepatier may be administered with or without ribavirin. In clinical studies, 95% of patients who were not previously treated for their hepatitis C virus were cured after 12 weeks of Zepatier treatment. Cure was defined as undetectable levels of hepatitis C virus in the blood when measured three months after the completion of treatment. The FDA approved Zepatier in January, 2016.

• Zepatier is used with or without ribavirin (Rebetrol) for the treatment of chronic hepatitis C virus (HCV) types 1 or 4 infection in adults.

Common side effects include:

• Fatigue
• Headache
• Nausea
• Insomnia
• Diarrhea

Other side effects include:

• Abdominal pain
• Irritability
• Depression
• Anemia (when combined with ribavirin)
• Elevations in levels of liver enzymes
• Increased bilirubin
• Joint pain
• Shortness of breath
• Rash
• Reactivation of hepatitis B virus infection (HBV)

• The recommended dose of Zepatier is one tablet daily with or without food for 12 to 16 weeks.
• The duration of treatment depends on whether patients have been previously treated with ribavirin and interferon for their HCV, the presence or absence of treatment-resistant HCV, and the type of HCV infection. Patients should be tested for the presence of resistant HCV prior to starting treatment to determine the correct dosage and duration of treatment.
• The recommended duration of treatment for most patients is 12 weeks. Those who fall into the following two categories are treated for 16 weeks:
• People with genotype 1a infection, treatment-naive or previously treated with peginterferon and ribavirin, and have resistant viruses: 16 weeks treatment.
• People with genotype 4 infection and previously treated with peginterferon (Pegasys) and ribavirin: 16 weeks treatment.

Zepatier has many drug interactions, for example:

Rifampin and St. John's wort may reduce blood levels of Zepatier by increasing its metabolism (break-down) in the intestine. Therefore, Zepatier should not be combined with rifampin or St. John's wort. Other drugs that also may reduce blood levels of Zepatier include:

• nafcillin (Nafcil)
• bosentan (Tracleer)
• carbamazepine (Tegretol, Tegretol XR , Equetro, Carbatrol)
• phenytoin (Dilantin, Dilantin-125)
• phenobarbital, oxcarbazepine (Tripetal)
• rifampin, tipranavir (Aptivus)
• ritonavir (Norvir)
• efavirenz (Sustiva)
• atazanavir (Reyataz)
• darunavir (Prezista)
• lopinavir/ritonavir (Kaletra)
• saquinavir (Invirase)
• etravirine (Intelence)
• modafanil (Provigil)

Combining Zepatier with cyclosporine or ketoconazole may increase the risk of liver enzyme elevations because cyclosporine increases blood levels of grazoprevir. Zepatier should not be combined with cyclosporine.

Zepatier increases blood levels of atorvastatin (Lipitor), rosuvastatin (Crestor), and possibly other statins. The dose of atorvastatin should not exceed a daily dose of 20 mg and the dose of Crestor should not exceed 10 mg daily when they are combined with Zepatier.

• Zepatier has not been adequately evaluated in pregnant women. However, ribavirin which may be combined with this drug should not be used by pregnant women or their male partners.
• It is not known whether this drug is secreted into breast milk.

What preparations of Zepatier are available?

• Tablets (elabsvir and grazoprevir): 50/100 mg

How should I keep Zepatier stored?

• This drug should be stored at room temperature, between 15 C to 30 C (59 F to 86 F).