NutriStack
Ivabradine and St. John's Wort, a conflict.
St. John's Wort can induce CYP3A4 and P-glycoprotein, and systematic reviews identify ivabradine as a drug whose exposure can be reduced by this herb. Lower ivabradine exposure may reduce heart-rate control and antianginal or heart-failure benefit. The effect can persist after stopping St. John's Wort because enzyme induction takes time to reverse.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- Ivabradine and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Moderate
- Source citations
- 3 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 can induce CYP3A4 and P-glycoprotein, and systematic reviews identify ivabradine as a drug whose exposure can be reduced by this herb. Lower ivabradine exposure may reduce heart-rate control and antianginal or heart-failure benefit. The effect can persist after stopping St. John's Wort because enzyme induction takes time to reverse.
Mechanism. Hyperforin-containing St. John's Wort activates pregnane X receptor, inducing CYP3A4 and P-glycoprotein. Ivabradine and its active metabolite undergo CYP3A4 metabolism, so induction can lower systemic exposure and blunt pharmacodynamic heart-rate reduction.
Recommendation. Avoid St. John's Wort while taking ivabradine unless your prescriber specifically approves and monitors the combination. Do not use dose spacing as a workaround because this is an enzyme and transporter induction interaction. Tell your clinician if you start or stop St. John's Wort so heart rate, symptoms, and ivabradine dosing can be reassessed.
Sources (3)
- Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798. PMID 19719333
- Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226. PMID 31742659
- Lang J, Vincent L, Chenel M, Ogungbenro K, Galetin A. Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method. AAPS J. 2020;22(6):129. PMID 33033962
Stack Score
How this pair moves the number.
Effect on the composite score
If both Ivabradine 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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