Major
Established
Description
Metronidazole markedly potentiates warfarin anticoagulation, leading to supratherapeutic INR levels and an elevated risk of serious bleeding.
Mécanisme
Metronidazole inhibits CYP2C9, the principal enzyme for S-warfarin metabolism, and may also inhibit CYP3A4, reducing warfarin clearance.
Signification clinique
INR increases of 50–200% have been documented; case reports of intracranial and GI hemorrhage exist.
Prise en charge
Reduce warfarin dose by ~25–50% when metronidazole is started; monitor INR every 2–3 days during therapy and for 1 week after stopping. Topical or vaginal metronidazole carries less risk than systemic.