NutriStack
St. John's Wort and Tadalafil, a conflict.
St. John's Wort can induce CYP3A4, the main metabolic pathway for tadalafil. This may lower tadalafil exposure and reduce its effectiveness for erectile dysfunction, BPH symptoms, or pulmonary hypertension indications. The risk is most relevant with daily or repeated St. John's Wort use, because enzyme induction builds over days and can persist after stopping.
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
- St. John's Wort and Tadalafil
- 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 can induce CYP3A4, the main metabolic pathway for tadalafil. This may lower tadalafil exposure and reduce its effectiveness for erectile dysfunction, BPH symptoms, or pulmonary hypertension indications. The risk is most relevant with daily or repeated St. John's Wort use, because enzyme induction builds over days and can persist after stopping.
Mechanism. Tadalafil is cleared predominantly by hepatic CYP3A metabolism. St. John's Wort activates pregnane X receptor pathways and induces CYP3A activity, increasing clearance of CYP3A substrates and lowering drug exposure.
Recommendation. Avoid St. John's Wort while using tadalafil unless your prescriber specifically approves it. If you stop St. John's Wort, do not change tadalafil dosing on your own; enzyme activity may take about a week or longer to normalize.
Sources (2)
- Forgue ST, Patterson BE, Bedding AW, Payne CD, Phillips DL, Wrishko RE, Mitchell MI. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006;61(3):280-288. PMID 16487221
- Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504. PMID 13129991
Stack Score
How this pair moves the number.
Effect on the composite score
If both St. John's Wort and Tadalafil 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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