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

Summary Background Drug–drug interactions ( DDI s) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct‐acting anti‐virals ( DAA s). Both currently approved DAA s, the protease inhibitors ( PI s) telaprevir ( TVR ) and boceprevir ( BOC ), are substrates and inhibitors of P‐glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDI s. Aim To analyse the risk for DDI s 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 DDI s 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 DDI s was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDI s between a PI and drugs newly prescribed during anti‐viral therapy were considerable in 42% of the patients. Suspected DDI s 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 DDI s if treated with a protease inhibitor , but only in a minority of cases co‐medication is strictly incompatible. Overall, the challenge of DDI s is time‐consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment.