NutriStack
Ranolazine and St. John's Wort, a conflict.
St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein. Ranolazine is extensively metabolized by CYP3A and is also linked to transporter-mediated drug interactions, so induction can reduce ranolazine exposure and antianginal benefit. Starting or stopping St. John's Wort can make symptom control less predictable.
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
- Ranolazine and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Emerging
- 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 · Emerging evidence
Conflict
What is happening. St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein. Ranolazine is extensively metabolized by CYP3A and is also linked to transporter-mediated drug interactions, so induction can reduce ranolazine exposure and antianginal benefit. Starting or stopping St. John's Wort can make symptom control less predictable.
Mechanism. Hyperforin from St. John's Wort activates PXR, increasing CYP3A4 and P-glycoprotein expression. Ranolazine is primarily cleared by CYP3A metabolism, so induction is expected to lower ranolazine concentrations and reduce late sodium current inhibition in ischemic myocardium.
Recommendation. Avoid St. John's Wort while taking ranolazine. If you have already combined them, tell your prescriber, especially if angina, exercise tolerance, or palpitations changed. Do not try to fix this by spacing doses because enzyme induction persists throughout the day.
Sources (3)
- Jerling M. Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-491. PMID 16640453
- 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
- Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798. PMID 19719333
Stack Score
How this pair moves the number.
Effect on the composite score
If both Ranolazine 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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