What supplements should a person on Clopidogrel and Apixaban (Elequis) avoid?

Supplements to Avoid While Taking Clopidogrel and Apixaban

Patients taking clopidogrel and apixaban together should avoid supplements that increase bleeding risk, particularly NSAIDs, St. John's wort, vitamin E in high doses, fish oil/omega-3 fatty acids in high doses, ginkgo biloba, garlic supplements, ginger supplements, and turmeric/curcumin supplements.

Critical Drug-Supplement Interactions

St. John's Wort - Absolute Avoidance Required

• St. John's wort must be completely avoided as it is a combined P-gp and strong CYP3A4 inducer that will significantly decrease apixaban exposure, increasing the risk of stroke and thromboembolic events 1
• This interaction reduces the effectiveness of apixaban, potentially leaving patients unprotected against clot formation 1

NSAIDs - Significantly Increases Bleeding Risk

• Avoid all NSAIDs (ibuprofen, naproxen, aspirin in supplement doses) as they dramatically increase bleeding risk when combined with both anticoagulants and antiplatelets 2
• The combination of anticoagulants with NSAIDs increases gastrointestinal and intracranial bleeding complications 2
• In the APPRAISE-2 trial, the combination of apixaban with antiplatelet therapy showed major bleeding rates of 5.9% per year versus 2.5% with placebo 1

Herbal Supplements That Increase Bleeding

High-Risk Herbal Products

• Ginkgo biloba: Inhibits platelet function and increases bleeding risk when combined with anticoagulants 2
• Garlic supplements: Have antiplatelet effects that compound bleeding risk with clopidogrel and apixaban 2
• Ginger supplements: Possess antiplatelet properties that increase hemorrhagic complications 2
• Turmeric/curcumin: Has anticoagulant effects that potentiate bleeding risk 2

Fish Oil and Omega-3 Fatty Acids

• High-dose fish oil supplements (>3 grams daily) should be avoided as they have antiplatelet effects 2
• Lower doses may be acceptable but require discussion with the prescribing physician 2

Vitamin E

• High-dose vitamin E supplements (>400 IU daily) should be avoided due to antiplatelet effects 2
• Dietary vitamin E from food sources is generally safe 2

Understanding the Bleeding Risk Context

Baseline Risk with This Combination

• The combination of apixaban and clopidogrel carries a significantly elevated bleeding risk, with major bleeding rates of 3.2-4.3% annually even without additional supplements 3
• Any supplement that further increases bleeding risk should be avoided given this already elevated baseline 3
• Advanced age, history of bleeding, peptic ulcer disease, and renal impairment further amplify this risk 2

Clinical Evidence for Avoidance

• In patients receiving dual antiplatelet therapy with apixaban, major bleeding rates reached 5.9% per year, leading to early trial termination 1
• The European Society of Cardiology guidelines explicitly recommend avoiding combinations that increase bleeding risk in patients on anticoagulants and antiplatelets 2

Additional Supplements Requiring Caution

Potentially Problematic Supplements

• Feverfew: Has antiplatelet properties 2
• Dong quai: Contains coumarins with anticoagulant effects 2
• Danshen: Has anticoagulant and antiplatelet properties 2
• Ginseng: May affect platelet function 2

Monitoring and Risk Mitigation

Essential Protective Measures

• Proton pump inhibitor (PPI) therapy should be considered to reduce gastrointestinal bleeding risk, particularly in patients ≥75 years or with history of GI bleeding 2
• Patients must be educated to recognize bleeding symptoms including unusual bruising, blood in urine or stool, prolonged bleeding from cuts, and severe headaches 2

Renal Function Considerations

• Renal impairment increases bleeding risk with apixaban and requires dose adjustment 2, 1
• Supplements should be avoided even more stringently in patients with CrCl <30 mL/min 2

Common Pitfalls to Avoid

• Do not assume "natural" supplements are safe - many have potent anticoagulant or antiplatelet effects 2
• Avoid multiple supplements simultaneously as cumulative bleeding risk is poorly characterized 3
• Do not discontinue prescribed medications to take supplements - the combination of clopidogrel and apixaban is prescribed for specific high-risk conditions 2
• Always disclose all supplements to healthcare providers before any surgical or dental procedures 2