warfarin and rifampicin

Rifampicin is a potent inducer of the hepatic cytochrome P450 enzyme CYP2C9, which is the primary enzyme responsible for the metabolism of the more active S-enantiomer of warfarin. Induction of CYP2C9 increases warfarin metabolism, leading to significantly reduced plasma concentrations and a diminished anticoagulant effect.

Concurrent use results in a marked decrease in warfarin's anticoagulant effect, as reflected by a substantial fall in the International Normalised Ratio (INR). This may predispose patients to thromboembolic complications, such as stroke, deep vein thrombosis, or pulmonary embolism, if the warfarin dose is not appropriately increased.

Avoid co-prescription where possible. If combination is unavoidable, anticipate a two- to threefold increase in the warfarin dose and monitor INR closely, particularly during the first week of rifampicin therapy and again after rifampicin is stopped. Consider alternative antibiotics with less enzyme-inducing potential or consider alternative anticoagulation strategies, such as a direct oral anticoagulant, where appropriate.

This interaction is well established through numerous clinical reports and pharmacokinetic studies. The magnitude of enzyme induction is consistent, and the clinical consequence of reduced anticoagulation is widely recognised in clinical practice guidelines and prescribing information for both drugs.