NutriStack
Apixaban and St. John's Wort, a conflict.
St. John's Wort potently induces CYP3A4 and P-glycoprotein, both of which are major pathways for apixaban metabolism and transport. This induction can reduce apixaban plasma levels by 50% or more, potentially rendering the anticoagulant ineffective and increasing the risk of thromboembolic events.
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
- Apixaban and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Strong
- Source citations
- 2 sources
- Stack Score effect
- −10 to your Stack Score (per scored conflict row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Conflict · Strong evidence
Conflict
What is happening. St. John's Wort potently induces CYP3A4 and P-glycoprotein, both of which are major pathways for apixaban metabolism and transport. This induction can reduce apixaban plasma levels by 50% or more, potentially rendering the anticoagulant ineffective and increasing the risk of thromboembolic events.
Mechanism. Hyperforin activates PXR, upregulating CYP3A4 and P-glycoprotein expression. Apixaban is a CYP3A4 substrate and P-gp substrate, so increased metabolism and efflux significantly reduce its bioavailability and plasma concentration.
Recommendation. Avoid combining St. John's Wort with apixaban. The FDA and EMA both list strong CYP3A4 inducers as contraindicated with DOACs. Discuss alternative mood support options with your prescriber.
Sources (2)
- Vakkalagadda B et al. Effect of rifampin on the pharmacokinetics of apixaban, a selective factor Xa inhibitor. Am J Ther. 2016;23(2):e460-467. PMID 25756467
- Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504. PMID 13129991
Stack Score
How this pair moves the number.
Effect on the composite score
If both Apixaban and St. John's Wort are in the same stack, this pair applies −10 to your Stack Score (per scored conflict row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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