Peginterferon-alpha 2a (40 kDa)/ribavirin combination for the treatment of chronic hepatitis C infection.

Chronic hepatitis C is the leading cause of liver disease and liver-related mortality in the western world. Treatment of this chronic viral infection has considerably improved with the introduction of ribavirin-interferon combination therapy. Ribavirin (Copegus, Rebetol) is a synthetic nucleoside analogue with broad antiviral effects. It is absorbed readily upon oral administration with meals. Daily doses of up to 1200 mg are usually well-tolerated, causing dose-dependent haemolysis, reversible with dose reduction in most patients, in particular in those with renal insufficiency. In the circulation it is bound to erythrocytes, and eliminated by phosphorylation and deribolysation. The drug accumulates in blood with renal insufficiency. Impairment of hepatic function does not influence drug levels in the circulation. In animal studies, teratogenic and reproductive toxicity was shown. In chronic hepatitis C virus infection, monotherapy with ribavirin has no effect on concentrations of viral RNA or liver histology. Combination therapy with pegylated interferon-alpha2a (40 kDa) (Pegasys) produces significantly higher sustained virological response rates in infections with all viral genotypes, even in advanced stages of liver disease compared pegylated interferon-alpha2a monotherapy, adverse effects and quality of life are not significantly different.