NutriStack
Fexofenadine and St. John's Wort, a caution.
St. John's Wort can change fexofenadine exposure through transporter effects. A single St. John's Wort dose increased fexofenadine peak concentration by 45%, while high-hyperforin repeated use has been associated with lower fexofenadine exposure from peripheral P-glycoprotein induction. The direction can depend on dose, hyperforin content, and duration of use, making allergy control and side effects 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
- Fexofenadine and St. John's Wort
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. St. John's Wort can change fexofenadine exposure through transporter effects. A single St. John's Wort dose increased fexofenadine peak concentration by 45%, while high-hyperforin repeated use has been associated with lower fexofenadine exposure from peripheral P-glycoprotein induction. The direction can depend on dose, hyperforin content, and duration of use, making allergy control and side effects less predictable.
Mechanism. Hyperforin-rich St. John's Wort activates pregnane X receptor signaling and can induce intestinal P-glycoprotein, while acute exposure may inhibit P-glycoprotein before induction develops. Fexofenadine is a transporter-dependent antihistamine, so both inhibition and induction can alter its pharmacokinetics.
Recommendation. Avoid starting St. John's Wort casually while taking fexofenadine every day. If you use both, keep the St. John's Wort product and dose stable, monitor allergy control and drowsiness, and tell your prescriber or pharmacist because St. John's Wort has broader drug-interaction risks. Stop St. John's Wort and reassess if fexofenadine seems suddenly weaker or more side-effect prone.
Sources (3)
- Wang Z, Hamman MA, Huang SM, Lesko LJ, Hall SD. Effect of St John's wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther. 2002;71(6):414-420. PMID 12087344
- El Biali M, Wolfl-Duchek M, Jackwerth M, et al. St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier. Clin Transl Sci. 2024;17(5):e13804. PMID 38700454
- 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
Stack Score
How this pair moves the number.
Effect on the composite score
If both Fexofenadine and St. John's Wort are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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