Telaprevir: An oral protease inhibitor for hepatitis C virus infection

Purpose. The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, drug interactions, viral drug resistance, dosage and administration, and place in therapy of telaprevir are reviewed. Summary. Telaprevir is an oral NS3/4A protease inhibitor that was recently approved by the Food and Drug Administration for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in adult patients with compensated liver disease, including cirrhosis. In Phase II clinical trials, triple therapy (telaprevir with peginterferon alfa and ribavirin) demonstrated 20-39% higher rates of sustained virological response (SVR) versus standard therapy (peginterferon alfa and ribavirin) in patients with chronic HCV genotype 1. Higher SVR rates were observed in treatment-naive patients or patients who did not respond to prior therapy (did not achieve SVR). Phase III studies also found improved SVR rates in patients treated with triple therapy. Telaprevir is recommended in combination with peginterferon alfa-2a and ribavirin for treatment-naive patients and patients who did not previously respond to peginterferon alfa-2a and ribavirin therapy. Telaprevir is a substrate and inhibitor of cytochrome P-450 (CYP) isoenzyme 3A4 and P-glycoprotein. Drugs that induce or inhibit CYP3A4 may affect concentrations of telaprevir, resulting in reduced efficacy or increased concentrations of telaprevir (and an increased risk for adverse reactions). The most common adverse events reported with telaprevir monotherapy versus placebo were diarrhea, nausea, fatigue, and dry skin. Conclusion. Telaprevir, an HCV NS3/4A protease inhibitor, has been shown to be effective in increasing SVR rates when used with peginterferon alfa and ribavirin in patients with chronic HCV genotype 1 infection, regardless of treatment history.