Ribavirin (RBV) is an
antiviral nucleoside analogue commonly used in combination with
interferon for the treatment of
chronic hepatitis C. Severe
anemia develops in about 10% of treated patients, and requires close monitoring of
hemoglobin and often RBV
dose reduction, which may compromise sustained virologic response.
Anemia is likely related to extensive RBV accumulation in erythrocytes subsequent to active unidirectional transmembraneous transport. RBV exerts its toxicity through an inhibition of intracellular energy metabolism and oxidative membrane damage, leading to an accelerated
extravascular hemolysis by the reticulo-endothelial system. Concentration-dependent toxicity and improvement of
anemia upon
dose-reduction point towards the importance of pharmacokinetic factors for RBV-induced
anemia. On the other hand, pronounced variability in the correlation between RBV concentration and Hb reduction limits the prediction of
anemia based on plasma or erythrocyte concentrations in individual patients and points towards additional factors determining individual susceptibility to RBV-induced
anemia. Recent studies suggest that erythrocyte oxidative defense mechanisms may play an important role in RBV-induced
anemia. Clinical risk factors for severe RBV-induced
anemia include impaired renal function, high age, high dose per
body weight and female gender. Determination of RBV concentrations has little value in the management of
anemia. The only proven effective prevention of RBV-induced
anemia is the concomitant administration of
erythropoietin. Future research on RBV pharmacokinetics and pharmacodynamics, as well as erythrocyte
antioxidant defense mechanisms may improve safety and efficacy of RBV
therapy and guide the development of new treatments for RBV-induced
anemia and alternative
antiviral agents.