Is it safe to take Ashwagandha with Clopidogrel and Apixaban (Eliquis)?

Ashwagandha Combined with Clopidogrel and Apixaban

Avoid taking Ashwagandha with the combination of clopidogrel and apixaban due to unacceptable compounded bleeding risk from triple antithrombotic therapy. 1

Primary Safety Concern: Compounded Bleeding Risk

The combination of clopidogrel (antiplatelet) and apixaban (anticoagulant) already creates substantial bleeding risk before adding any herbal supplement:

• Dual antithrombotic therapy (antiplatelet plus anticoagulant) increases major bleeding events 3.4-fold compared to monotherapy, with bleeding requiring transfusion or surgical intervention being the primary concern 1
• Adding Ashwagandha—which has antiplatelet properties similar to garlic supplements—creates triple antithrombotic therapy with unacceptable bleeding risk 1
• The combination of anticoagulant and antiplatelet therapy increases major extracranial bleeding with an odds ratio of 2.4 (95% CI: 1.4 to 4.1), meaning as few as 67 patients need treatment to cause 1 additional major bleeding event 2

Clinical Decision Algorithm

Step 1: Immediate Action

• Discontinue Ashwagandha immediately if the patient is currently taking it with clopidogrel and apixaban 1

Step 2: Reassess Dual Therapy Indication

• Verify that dual therapy (clopidogrel + apixaban) is still clinically indicated, as this combination should only be used in specific high-risk scenarios such as atrial fibrillation patients with recent coronary stenting 1
• The combination should only be prescribed when benefits clearly outweigh risks 1

Step 3: Implement Gastroprotection

• Prescribe a proton pump inhibitor (PPI) such as pantoprazole, dexlansoprazole, or lansoprazole to reduce gastrointestinal bleeding risk 1
• When anticoagulants are combined with antiplatelet agents, concomitant PPIs should be prescribed 2

Step 4: Risk Stratification

Monitor closely if the patient has any of these high-risk features 1:

• Age over 75 years
• History of gastrointestinal bleeding
• Peptic ulcer disease
• Renal impairment
• Body weight <60 kg

Understanding the Baseline Risk

Even without Ashwagandha, the clopidogrel-apixaban combination carries significant bleeding risk:

• In a retrospective cohort study of 3,628 apixaban+clopidogrel users, the major bleeding rate was 7.38 per 100 person-years 3
• Clopidogrel alone increases upper GI bleeding risk (adjusted RR 2.8; 95% CI 1.9 to 4.2) 2
• Approximately 33% of patients on apixaban take at least one over-the-counter product with potentially serious interactions daily, and many lack knowledge about bleeding risks 4

Common Pitfalls to Avoid

• Do not assume herbal supplements are safe simply because they are "natural"—Ashwagandha has pharmacologically active antiplatelet effects 1
• Do not fail to ask about herbal supplements during medication reconciliation, as patients often do not volunteer this information 4
• Do not withhold PPI therapy due to concerns about clopidogrel interaction—the bleeding risk reduction from PPIs outweighs any theoretical reduction in clopidogrel efficacy 2
• Do not add aspirin to this regimen unless there is acute vascular disease indication, as bleeding events increase without clear benefit 5

Alternative Considerations

If the patient requires only one antithrombotic agent:

• Apixaban monotherapy may be sufficient for stroke prevention in atrial fibrillation without adding clopidogrel 5
• Clopidogrel monotherapy may be appropriate for coronary artery disease without atrial fibrillation 2

The decision to continue dual therapy should be based on specific cardiovascular indications (such as recent stent placement in a patient with atrial fibrillation requiring anticoagulation), not routine practice 1.