What supplements should be avoided when taking clopidogrel and apixaban (Eliquis)?

Supplements to Avoid with Clopidogrel and Apixaban (Eliquis)

When taking clopidogrel and apixaban together, you must avoid NSAIDs (including ibuprofen and naproxen), aspirin (unless specifically prescribed for acute vascular disease), SSRIs/SNRIs, and herbal supplements that affect bleeding—particularly St. John's Wort, ginkgo biloba, garlic supplements, ginger, turmeric/curcumin, fish oil at high doses, and vitamin E supplements. 1, 2, 3

Over-the-Counter Medications to Avoid

NSAIDs (Highest Risk)

• Ibuprofen (Advil, Motrin) and naproxen (Aleve) must be avoided as they significantly increase bleeding risk when combined with anticoagulants and antiplatelets 1
• Even occasional use of NSAIDs poses substantial bleeding risk—in one study, 28.5% of patients on apixaban were taking these occasionally despite the danger 3
• If pain relief is needed, acetaminophen (Tylenol) is the safer alternative 1

Aspirin

• Avoid aspirin unless your cardiologist has specifically prescribed it for acute coronary syndrome or recent stenting 1
• The combination of anticoagulants with dual antiplatelet therapy (aspirin + clopidogrel) increases bleeding events without clear benefit for stroke prevention in most patients 1
• In one study, 14.7% of patients on apixaban were inappropriately taking daily aspirin, and 64.7% of those were also consuming other interacting products 3

Antidepressants (SSRIs/SNRIs)

• SSRIs (like Prozac, Zoloft, Lexapro, Celexa) and SNRIs (like Effexor, Cymbalta) significantly increase bleeding risk when combined with anticoagulants and antiplatelets 1, 2
• While escitalopram doesn't affect apixaban metabolism through CYP3A4 pathways, it still increases bleeding risk through platelet dysfunction 2
• If you require an antidepressant, discuss alternatives with your psychiatrist that have less effect on platelet function 2

Dietary Supplements to Avoid

Herbal Products with Antiplatelet/Anticoagulant Effects

• St. John's Wort: Strong CYP3A4 inducer that can reduce apixaban levels, potentially leading to treatment failure 4
• Ginkgo biloba: Increases bleeding risk through antiplatelet effects 3
• Garlic supplements (not culinary amounts): Antiplatelet effects increase bleeding risk 3
• Ginger supplements (high doses): Antiplatelet properties 3
• Turmeric/Curcumin supplements: Antiplatelet and anticoagulant effects 3

Omega-3 and Vitamin Supplements

• Fish oil/Omega-3 supplements at high doses (>3 grams daily): Antiplatelet effects that increase bleeding 3
• Vitamin E supplements (especially >400 IU daily): Interferes with platelet function 3
• Culinary amounts of these foods are generally safe; the concern is concentrated supplement forms 3

Other Supplements

• Glucosamine/Chondroitin: May potentiate warfarin effects and theoretically could affect other anticoagulants 3
• Coenzyme Q10: Potential interaction with anticoagulants 3

Critical Drug Interactions with Apixaban

Strong CYP3A4 and P-glycoprotein Inhibitors

• Ketoconazole, itraconazole, and ritonavir require apixaban dose reduction by 50% if you're taking 5 mg or 10 mg twice daily 4
• If already on apixaban 2.5 mg twice daily, avoid these medications entirely 4

Proton Pump Inhibitors (PPIs) with Clopidogrel

• Omeprazole (Prilosec) and esomeprazole (Nexium) must be avoided as they significantly reduce clopidogrel's antiplatelet effects 1, 5
• If you need acid suppression, use pantoprazole, lansoprazole, or dexlansoprazole instead, which have less pronounced effects on clopidogrel 5
• H2 receptor antagonists (like famotidine) are acceptable alternatives 1

What You Need to Know

Prevalence of Dangerous Combinations

• Research shows 97.5% of patients on apixaban use OTC products, with 33% taking at least one product with potentially serious interactions daily 3
• Approximately 66% of patients are uncertain or incorrect about bleeding risks from combining NSAIDs with anticoagulants 3
• 20.2% of patients take dietary supplements with potentially serious interactions daily 3

Bleeding Risk Factors

The combination of apixaban and clopidogrel already carries significant bleeding risk, which is further amplified by: 1, 2, 6

• Age ≥75 years
• Weight <60 kg
• Renal impairment (creatinine ≥1.5 mg/dL)
• History of gastrointestinal bleeding or peptic ulcer disease
• Concurrent use of any of the above-mentioned supplements or medications

If Bleeding Occurs

• Stop all anticoagulants, antiplatelets, and interacting supplements immediately 2
• Apixaban's effect diminishes over 24-48 hours in patients with normal kidney function 2
• Reversal agents like andexanet alfa are reserved only for life-threatening bleeding, not routine bleeding events 2

Common Pitfall

The most dangerous mistake is assuming "natural" supplements are safe—many patients don't report supplement use to their doctors, and less knowledge about interactions is associated with greater supplement use 3. Always disclose every supplement, vitamin, and OTC medication to your healthcare team.