Supplement × Prescription·contraindicated·Strong evidence
St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Itraconazole exposure or undermine therapy.
Every entry follows the same shape: what is happening, the mechanism, and the recommendation.
What is happening. St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Itraconazole exposure or undermine therapy.
Mechanism. Hyperforin induces CYP3A4 and P-glycoprotein, which can reduce exposure to susceptible drugs.
Recommendation. Avoid St. John's Wort with Itraconazole.
What is happening. St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein. Itraconazole is extensively metabolized by CYP3A4, so concomitant use markedly increases itraconazole clearance and can reduce plasma concentrations to subtherapeutic levels, risking antifungal treatment failure.
Mechanism. Hyperforin in St. John's Wort activates the pregnane X receptor, inducing CYP3A4 and P-glycoprotein expression, which accelerates itraconazole metabolism and efflux and lowers systemic exposure.
Recommendation. Avoid combining St. John's Wort with itraconazole. If an antidepressant or mood supplement was being used, discuss alternatives with the prescriber. Because enzyme induction persists for one to two weeks after stopping St. John's Wort, do not assume immediate normalization of itraconazole levels.
Effect on the composite score
If both Itraconazole and St. John's Wort are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are at /methodology/stack-score.
Every claim on this page is cited. PMIDs link straight to PubMed.
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