Adverse effects and other safety aspects of the hepatitis C antivirals.

The preferred treatment for patients with chronic hepatitis C, either treatment-naive, relapsers or nonresponders to IFN monotherapy, is now IFN-ribavirin combination treatment. The adverse effects of IFN are well established and familiar to hepatologists all over the world. More than 25,000 patients worldwide have been treated with combination therapy. Patients re-treated with a combination regimen are more likely to tolerate IFN better than treatment-naive patients, probably due to better case selection. The safety profile of regimens containing IFN-alpha plus ribavirin is generally consistent with the safety profile of each agent when employed in monotherapy; there is little or no synergistic toxicity. Anorexia, dyspnoea, cough, pruritus and rash are the only adverse events reported at a consistently higher frequency with combination treatment, and are usually mild to moderate in severity and rarely result in dose reductions or discontinuation. The primary cause of dose reduction for combination therapy is haemolytic anaemia, which can be managed effectively. The most common reason for discontinuation of therapy for either type of therapy is psychiatric problems, especially depression, which seems to be closely related to the duration of treatment. In patients receiving combination therapy, anaemia and depression need close monitoring, and dose modification in some cases. Strict guidelines for dose reduction and discontinuation are essential to prevent serious adverse events. Because of the teratogenic risk from ribavirin, pregnancy is contraindicated in patients or their partners during and 6 months after treatment.