Antiviral Agent
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk (Contraindicated 3-Drug Combination)
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity (3-Drug Combination)
PREGNANCY SUMMARY
No reports describing the use of boceprevir in human pregnancy have been located. The animal data suggest low risk. However, the indication for boceprevir involves the combined use with ribavirin and peginterferon alfa. Although peginterferon alfa is probably compatible with pregnancy (see Interferon Alfa), ribavirin is contraindicated because it has caused developmental toxicity in all animal species tested (see Ribavirin). The three-drug combination should be avoided in pregnancy.
FETAL RISK SUMMARY
Boceprevir, a mixture of two diastereomers administered orally, is an inhibitor of the hepatitis C virus protein serine protease. It is indicated, in combination with peginterferon alfa and ribavirin, for the treatment of chronic hepatitis C genotype 1 infection in adults with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. It is metabolized by the liver to inactive metabolites. Plasma protein binding is about 75% and the mean elimination plasma half-life is about 3.4 hours (1).
Reproduction studies with boceprevir alone have been conducted in rats and rabbits. AUC exposures in these species that were 11.8 and 2.0 times, respectively, the human exposure at the recommended dose of 800 mg 3 times daily produced no effects on fetal development. However, ribavirin causes dose-related teratogenicity or embryolethality in animals (see Ribavirin) and peginterferon alfa causes dose-related abortions in animals (see Interferon Alfa) (1).
Two-year carcinogenicity studies in rats and mice with boceprevir were negative. Similar studies in these species with ribavirin also were negative. Boceprevir was not genotoxic, but ribavirin was, in multiple assays. Ribavirin induced reversible testicular toxicity in animals and interferon alfa impaired fertility in females. Boceprevir caused reversible effects on fertility and early embryonic development in female rats, as well as dose-related testicular degeneration in male rats. This latter effect was not observed in mice and monkeys, and limited clinical monitoring has revealed no evidence of testicular toxicity in humans (1).
It is not known if boceprevir crosses the human placenta. The molecular weight (about 520), moderate plasma protein binding and elimination half-life suggest that the agent will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
Studies describing the use of boceprevir during human lactation have not been located. The molecular weight (about 520), moderate plasma protein binding (about 75%) and elimination half-life suggest that the agent will be excreted into breast milk. The effects of this exposure on a nursing infant are unknown. However, boceprevir is always combined with ribavirin and peginterferon alfa (see Ribavirin and Interferon Alfa). The latter agent is known to be excreted into breast milk and ribavirin is probably excreted. If a woman taking this therapy is breastfeeding, her nursing infant could be exposed to all three agents. Thus, the best course of action is to not breastfeed.
Reference
1.Product information. Victrelis. Schering Corporation, 2012.