NutriStack
Clopidogrel and St. John's Wort, a caution.
St. John's Wort induces CYP3A4 and CYP2C19, which are the key enzymes responsible for converting clopidogrel from its inactive prodrug form to its active metabolite. A clinical study showed that St. John's Wort decreased platelet aggregation and increased platelet inhibition in both clopidogrel hyporesponders and regular patients, effectively enhancing clopidogrel's antiplatelet effect. While this might seem beneficial for hyporesponders, the unpredictable potentiation increases bleeding risk.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Clopidogrel and St. John's Wort
- Pair type
- Caution
- Evidence (highest tier)
- Strong
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Strong evidence
Caution
What is happening. St. John's Wort induces CYP3A4 and CYP2C19, which are the key enzymes responsible for converting clopidogrel from its inactive prodrug form to its active metabolite. A clinical study showed that St. John's Wort decreased platelet aggregation and increased platelet inhibition in both clopidogrel hyporesponders and regular patients, effectively enhancing clopidogrel's antiplatelet effect. While this might seem beneficial for hyporesponders, the unpredictable potentiation increases bleeding risk.
Mechanism. Clopidogrel is a prodrug requiring two-step hepatic activation, primarily by CYP2C19 and CYP3A4. St. John's Wort's hyperforin induces both enzymes via PXR activation, potentially increasing conversion of clopidogrel to its active thiol metabolite. A clinical study confirmed increased CYP3A4 activity and enhanced platelet inhibition with concurrent St. John's Wort.
Recommendation. Avoid self-prescribing St. John's Wort with clopidogrel. While it may enhance clopidogrel activation, the unpredictable magnitude of increased antiplatelet effect raises bleeding risk. If your prescriber has identified clopidogrel hyporesponsiveness, discuss this potential interaction with them rather than self-managing with St. John's Wort.
Sources (2)
- Lau WC et al. The effect of St John's Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. J Cardiovasc Pharmacol. 2011;57(1):86-93. PMID 20980920
- Lun R, Dhaliwal S, Zitikyte G, Roy DC et al.. Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis. JAMA Neurology. 2022. PMID 34870698
Stack Score
How this pair moves the number.
Effect on the composite score
If both Clopidogrel and St. John's Wort are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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