Zepatier Hepatitis C Drug Information

Classification

Zepatier (elbasvir/grazoprevir) is a fixed dose combination drug used in the treatment of chronic hepatitis C (HCV) infection. The two drugs that comprise Zepatier (elbasvir, grazoprevir) work by blocking both a protein (NS5a) and an enzyme (NS3/4a protease) vital to the replication of the virus.

Zepatier was approved on January 28, 2016 by the U.S. Food and Drug Administration (FDA) for use in adults 18 years or over with HCV genotype 1 or 4 infection, including those with cirrhosis.

It is approved for use in both untreated (treatment-naïve) or previously treated (treatment-experienced) patients, depending on the HCV genotype and treatment status.

Efficacy

Zepatier is reported to have exceptional cure rates in Phase II human trials. An HCV cure is defined as sustaining an undetectable viral load for 24 weeks following completion of therapy (also known as a sustained virologic response, or SVR).

The overall SVR rates ranged from 94% to 97% in patients with HCV genotype 1 infection, while patients with genotype 4 infection were reported to have SVR rates of 97% to 100%.

Dosage

One tablet (50mg/100mg) taken daily with or without food. Zepatier tablets are oval-shaped, beige-colored and film-coated, with "770" embossed on one side.

Prescribing Recommendations

Zepatier is prescribed either with or without ribavirin for genotype 1 or 4 infection. Unlike previous HCV therapies, peginterferon (a drug associated with often intolerable side effect) is not required.

Prior to initiation of therapy, genetic testing may be performed to determine whether you have a type of virus that is resistant to the elbasvir component of Zepatier (known as an NS5a resistance-associated polymorphism).

Duration of therapy ranges from 12-16 weeks, depending on HCV genotype and treatment status.

Common Side Effects

The most common side effects associated with Zepatier use (occurring in over 5% patients) are:

• Fatigue
• Headache
• Nausea

When used with ribavirin, the most commonly reported treatment side effects (occurring in over 5% patients) include:

• Headache
• Fatigue
• Anemia
• Nausea
• Itchiness
• Indigestion
• Shortness of breath
• Insomnia
• Muscle pain
• Decreased appetite
• Cough
• Irritability
• Rash

Drug Interactions

The following medications should not be used when taking Zepatier as they may cause significant drug-drug interactions:

• Antibiotics: nafcillin
• Anticonvulsives: Dilantin (phenytoin), Tegretol (carbamazepine)
• Antifungals: Nizoral oral tablets (ketoconazole)
• Anti-hypertensive drugs: Tracleer (bosentan)
• Herbal products: St. John's Wort
• HIV antiretroviral drugs: Aptivus (tipranavir), Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide), Intelence (etravirine), Invirase (saquinavir), Kaletra (lopinavir, ritonavir), Prezista (darunavir), Reyataz (atazanvir), Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disproxil), Sustiva (efavirenz), 
• Immunosuppressant drugs used to prevent organ transplant rejection: cyclosporine

• Rifampin-based drugs used in tuberculosis treatment: Mycobutin,Priftin, Rifater, Rifamate, Rimactane, Rifadin

Treatment Considerations

It has been reported in clinical studies that 1% of patients on Zepatier developed a severe elevation of liver enzymes indicative of liver toxicity, generally at or after the eighth week of therapy. As such, liver-related blood tests need to be performed before the initiation of therapy and regularly during the course of HCV therapy.

Zepatier should not be prescribed to patients with severe liver impairment.

The use of ribavirin is contraindicated in pregnancy and should not be prescribed either with Zepatier or any other hepatitis C drug. Female patients on a ribavirin-based therapy should be advised to avoid pregnancy and to use at least two non-hormonal methods of contraception during the course of therapy and for six months following completion of therapy.