The clinical significance of drug–drug interactions in the era of direct-acting anti-viral agents against chronic hepatitis C
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.
To analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre.
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.
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.
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.