Major
Established
Descrição
Metronidazole markedly potentiates warfarin anticoagulation, leading to supratherapeutic INR levels and an elevated risk of serious bleeding.
Mecanismo
Metronidazole inhibits CYP2C9, the principal enzyme for S-warfarin metabolism, and may also inhibit CYP3A4, reducing warfarin clearance.
Significância Clínica
INR increases of 50–200% have been documented; case reports of intracranial and GI hemorrhage exist.
Conduta
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.