Zepatier for the treatment of chronic hepatitis C virus in adult patients, positive opinion from CHMP
The Committee for Medicinal Products for Human Use ( CHMP ) of the European Medicines Agency ( EMA ) has adopted a positive opinion recommending approval of Zepatier ( Elbasvir and Grazoprevir ), an investigational, once-daily, fixed-dose combination tablet for the treatment of chronic hepatitis C virus ( HCV ) in adult patients.
Zepatier is a fixed-dose combination product containing elbasvir, a HCV NS5A inhibitor, and Grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated with or without Ribavirin for treatment of chronic HCV genotype 1 or 4 infection in adults. Zepatier is a single tablet taken once daily.
The recommended dosing is 12 or 16 weeks with or without Ribavirin, depending on HCV genotype, prior treatment history and, for patients with genotype 1a infection, presence of certain baseline NS5A resistance-associated polymorphisms. To determine dosage regimen and duration of Zepatier for genotype 1a patients, testing for the presence of virus with one or more baseline NS5A resistance-associated polymorphisms at positions 28, 30, 31, or 93 is recommended prior to initiating treatment.
Zepatier is not for use in patients with moderate or severe hepatic impairment ( Child Pugh B or C ). Zepatier is also not for use with organic anion transporting polypeptides 1B1/3 ( OATP1B1/3 ) inhibitors ( e.g., Atazanavir, Darunavir, Lopinavir, Saquinavir, Tipranavir, Cyclosporine ), strong cytochrome P450 3A ( CYP3A ) inducers ( e.g., Carbamazepine, Phenytoin, Rifampin, St. John’s Wort ), and Efavirenz.
Elevations of alanine transaminase ( ALT ) to greater than 5 times the upper limit of normal ( ULN ) occurred in 1% of subjects, generally at or after treatment week 8. These late ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy.
Healthcare professionals should perform hepatic lab testing on patients prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.
Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces.
Healthcare providers should consider discontinuing Zepatier if ALT levels remain persistently greater than 10 times ULN. Zepatier should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalized ratio.
In subjects receiving Zepatier for 12 weeks, the most commonly reported adverse reactions of all intensity ( greater than or equal to 5% in placebo-controlled trials ) were fatigue, headache and nausea.
In subjects receiving Zepatier with Ribavirin for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity ( greater than or equal to 5% ) were anemia and headache. ( Xagena )
Source: Merck, 2016