Warfarin: Drug Interactions

Major Interactions — Avoid or Monitor Closely

• ⚠Antiplatelet agents (aspirin, clopidogrel, prasugrel) — additive bleeding; major bleeding risk increases 3–7×; avoid unless clear benefit (e.g. mechanical valve + CAD)
• ⚠Amiodarone — strong CYP2C9 inhibition; INR increases 30–50%; reduce warfarin dose 30–50% and monitor INR weekly
• ⚠Fluconazole / voriconazole — potent CYP2C9 inhibition; INR may double; reduce warfarin by ~50% with daily monitoring
• ⚠Metronidazole — CYP2C9 inhibition + gut flora disruption; INR increase 50–100%
• ⚠NSAIDs — protein displacement + GI mucosal damage + antiplatelet effect; 3× increase in major GI bleeding

Moderate Interactions — Use With Caution

• •Rifampicin — powerful CYP induction; reduces warfarin effect up to 70%; requires dose doubling and weekly INR monitoring
• •Carbamazepine, phenytoin, phenobarbital — enzyme induction; reduces INR
• •Broad-spectrum antibiotics — gut flora disruption → reduced vitamin K2 → increased INR; most relevant in poor nutritional status
• •SSRIs — platelet inhibition; increases bleeding risk particularly with warfarin
• •Statins (fluvastatin, rosuvastatin) — CYP2C9 competition; modest INR increase
• •Vitamin K supplements — directly antagonise warfarin effect; disrupt INR control

Food & Drink Interactions

• •Vitamin K-rich foods (kale, spinach, broccoli, Brussels sprouts) — directly compete with warfarin; consistent intake matters more than restriction
• •Cranberry juice — CYP2C9 inhibition; reported significant INR elevations; limit or avoid
• •Alcohol — acute ingestion inhibits CYP2C9 (raises INR); chronic heavy use induces enzymes (lowers INR)

Monitoring Requirements

INR every 4–8 weeks at stable dose; more frequent with any drug, dose, or dietary change; patient education on consistent vitamin K intake and prompt reporting of drug changes