NutriStack
Fluconazole and St. John's Wort, a conflict.
St. John's Wort is a strong inducer of CYP3A4 (via PXR activation by hyperforin) and P-glycoprotein. Because fluconazole is partly metabolized by CYP3A4 and is itself a CYP3A4 inhibitor, St. John's Wort can lower fluconazole plasma levels and shorten its half-life, potentially leading to subtherapeutic exposure and treatment failure of a serious fungal infection.
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
- Fluconazole 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 is a strong inducer of CYP3A4 (via PXR activation by hyperforin) and P-glycoprotein. Because fluconazole is partly metabolized by CYP3A4 and is itself a CYP3A4 inhibitor, St. John's Wort can lower fluconazole plasma levels and shorten its half-life, potentially leading to subtherapeutic exposure and treatment failure of a serious fungal infection.
Mechanism. Hyperforin from St. John's Wort activates the pregnane X receptor (PXR), inducing CYP3A4 and P-glycoprotein. This accelerates clearance of CYP3A4 substrates including azole antifungals.
Recommendation. Do not take St. John's Wort during fluconazole therapy. If you were already taking it, stop and tell your prescriber so they can consider monitoring response or extending the course.
Sources (2)
- Moore LB, et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A. 2000;97(13):7500-2. PMID 10852961
- Nicolussi S, et al. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226. PMID 31742659
Stack Score
How this pair moves the number.
Effect on the composite score
If both Fluconazole 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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