Metronidazole × Warfarin

Metronidazole stereospecifically inhibits CYP2C9, the clearance route for S-warfarin (the more active stereoisomer). INR may double within 3–7 days of co-administration.

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

For short metronidazole courses (5–7 days), empirically reduce warfarin by 20–30% and check INR 3–4 days after starting and 7 days after stopping the antibiotic. For prolonged metronidazole therapy, titrate warfarin to INR.