Major
Clarithromycin × Warfarin
Macrolide antibiotic×Vitamin K antagonist anticoagulants
Mechanism
Clarithromycin inhibits CYP3A4 (a minor warfarin clearance route) and suppresses vitamin K-producing gut flora. INR rises 1.5- to 2-fold within 3–5 days of co-administration.
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
During clarithromycin therapy, empirically reduce warfarin by 20–30% and check INR 3–4 days after starting and 7 days after stopping the antibiotic. Alternative: azithromycin (minimal CYP3A4 and gut-flora impact).