A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients

Purpose. Chronic hepatitis C virus (HCV) is a major problem affecting up to 170 million people worldwide. Two protease inhibitors have recently been approved that will revolutionize treatment. Our objective was to summarize and evaluate the literature pertaining to the pharmacokinetics of boceprevir and telaprevir, in order to provide clinicians with insight into the management of actual and potential drug interactions. Summary. A standardized search using MEDLINE (1948-November 2011), EMBASE (1980-November 2011), IPA (1970-November 2011), Google, and Google Scholar that combined the search terms boceprevir, telaprevir, pharmacokinetics, drug interaction, and drug metabolism was performed. Manual reference searches of chosen articles were completed. Monographs and articles, conference proceedings, and abstracts were evaluated. Boceprevir and telaprevir are both substrates and inhibitors of cytochrome P450 3A4 and telaprevir is a substrate of p-glycoprotein. Levels of boceprevir are decreased in patients taking efavirenz but effects with other antiretrovirals are minimal or unknown. Coadministration with efavirenz may compromise telaprevir levels and should be avoided. Telaprevir may increase levels of cyclosporine, tacrolimus, atorvastatin, and amlodipine, which may expose patients to increased adverse effects. Conclusions. Significant drug-drug interactions occur with both boceprevir and telaprevir. Until studies are reported and experience is gained with these agents, clinicians will need to be careful when administering in high-risk populations and those receiving chronic therapy with interacting agents. Studies are urgently needed in HIV patients taking antiretrovirals and patients taking chronic immunosuppresion as these populations are at increased risk of experiencing clinically significant interactions.