The clinical significance of drug-drug interactions in the era of direct-acting anti-viral agents against chronic hepatitis C virus

Aliment Pharmacol Ther. 2013 Oct 16. doi: 10.1111/apt.12523. [Epub ahead of print]

Maasoumy B, Port K, Calle Serrano B, Markova AA, Sollik L, Manns MP, Cornberg M, Wedemeyer H.

Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Abstract

BACKGROUND: Drug-drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct-acting anti-virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P-glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.

AIM: To analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre.

METHODS: The first 115 consecutive patients selected for a PI therapy at Hannover Medical School were included. All changes to co-medication before and during PI treatment were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites and the respective prescribing information.

RESULTS: Out-patient medication contained 116 different drugs. Median number of drugs/patient was 2 (range 0-11). The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients. Suspected DDIs were managed by dose adjustments and discontinuation of co-medication in 7% and 21% of the patients respectively.

CONCLUSIONS: Many patients with chronic HCV genotype 1 infection are affected by potential DDIs if treated with a protease inhibitor, but only in a minority of cases co-medication is strictly incompatible. Overall, the challenge of DDIs is time-consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment.

© 2013 John Wiley & Sons Ltd.

PMID: 24127648 [PubMed - as supplied by publisher]

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