Prolonged induction of warfarin metabolism and a paradoxical INR response in a mitral valve replacement patient receiving rifampicin for infective endocarditis

Rifampicin induces multiple detoxification pathways, including those mediated by enzymes of the cytochrome P450 (CYP) family such as CYP2C9 and CYP3A4 [1], and is a known perpetrator of metabolic drug-drug interactions (mDDIs). Warfarin is a narrow therapeutic index anti-coagulant drug that is primarily cleared via CYP-mediated metabolism, and as such is a plausible victim of mDDIs with clinically relevant consequences. S-warfarin is primarily cleared by CYP2C9 while R-warfarin is exclusively cleared by CYP3A4 [2]. S-warfarin is 3-5 times more active than R-warfarin and is primarily responsible for the observed anticoagulant activity. While mDDIs involving rifampicin and warfarin have been reported [3-10], the appropriate schedule for warfarin dose reduction post cessation of rifampicin remains poorly defined and patients are at risk of both bleeding and thrombotic events during this period.