Heparin: Drug Interactions

Major Interactions — Avoid or Monitor Closely

• ⚠NSAIDs and antiplatelet agents (aspirin, clopidogrel) — additive bleeding risk; major bleeding increases 2–4×
• ⚠Other anticoagulants — contraindicated combination; dramatically increases haemorrhage risk
• ⚠Rifampicin — potent CYP3A4/P-gp inducer; reduces DOAC and warfarin levels by 50–90%
• ⚠Strong CYP3A4/P-gp inhibitors (ketoconazole, itraconazole) — contraindicated with rivaroxaban/apixaban at high-level inhibition

Moderate Interactions — Use With Caution

• •Amiodarone — CYP2C9 inhibition; increases warfarin INR 30–50%; also increases dabigatran levels
• •Fluconazole/voriconazole — strong CYP2C9 inhibition; may double warfarin effect
• •Carbamazepine, phenytoin, St. John's Wort — enzyme inducers; reduce warfarin and DOAC levels
• •Macrolide antibiotics (clarithromycin) — P-gp inhibition; increases dabigatran ~20%
• •SSRIs — platelet inhibition; combined bleeding risk

Food & Drink Interactions

• •Vitamin K-rich foods (leafy greens) — directly antagonise warfarin; consistency of intake matters more than restriction
• •Grapefruit juice — CYP3A4 inhibition increases rivaroxaban/apixaban; limit intake
• •Alcohol — acute inhibition of warfarin metabolism (raises INR); chronic heavy use induces enzymes (lowers INR)
• •Cranberry juice — possible CYP2C9 inhibition; reported INR elevations with warfarin

Monitoring Requirements

Warfarin: INR every 4–8 weeks at stable dose, target 2–3 (most indications) or 2.5–3.5 (mechanical valves). DOACs: renal function (eGFR) annually and at dose changes. All agents: signs of bleeding, bruising, haematuria