NutriStack
Clarithromycin and St. John's Wort, a conflict.
St. John's Wort is a potent inducer of CYP3A4, the primary enzyme that metabolizes clarithromycin. Co-administration substantially lowers clarithromycin serum levels and can result in treatment failure. The induction effect persists for days to weeks after stopping St. John's Wort.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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What the row says.
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At a glance
- Substances
- Clarithromycin and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Moderate
- 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 · Moderate evidence
Conflict
What is happening. St. John's Wort is a potent inducer of CYP3A4, the primary enzyme that metabolizes clarithromycin. Co-administration substantially lowers clarithromycin serum levels and can result in treatment failure. The induction effect persists for days to weeks after stopping St. John's Wort.
Mechanism. Hyperforin in St. John's Wort activates the pregnane X receptor (PXR), upregulating hepatic and intestinal CYP3A4 and P-glycoprotein. This dramatically accelerates clarithromycin clearance and can lower plasma concentrations below the minimum inhibitory concentration for target organisms.
Recommendation. Avoid St. John's Wort during clarithromycin therapy and for at least 2 weeks before starting. Use an alternative antibiotic or alternative antidepressant strategy if both are needed.
Sources (2)
- Kakuda TN, Schöller-Gyüre M, Hoetelmans RM. Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011;50(1):25-39. PMID 21142266
- Klotz U. Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist. Arzneimittelforschung. 2002;52(3):155-61. PMID 11963641
Stack Score
How this pair moves the number.
Effect on the composite score
If both Clarithromycin 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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