Major
Co-trimoxazole × Warfarin
Sulfonamide-trimethoprim combination×Vitamin K antagonist anticoagulants
Mechanism
Trimethoprim and sulfamethoxazole (the components of co-trimoxazole) both inhibit CYP2C9, the main S-warfarin clearance route. Co-trimoxazole additionally displaces warfarin from plasma protein binding. INR may rise 2- to 4-fold within 3–7 days.
Symptoms
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.
Management
For a short co-trimoxazole course (up to 7 days), empirically reduce warfarin by 30–50% and check INR every 3 days. For urinary tract infections in warfarin-treated patients, prefer nitrofurantoin or fosfomycin (minimal CYP2C9 impact).