The short answer
Have St. John’s wort reviewed before combining it with zileuton. Reduced zileuton levels and a protective spacing interval have not been established in a direct human study.
What this answer covers
Hypericum perforatum; extract and hyperforin content affect whether other-drug metabolic findings apply.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- zileuton
Why interaction review is reasonable
Zileuton is metabolized through several liver enzyme pathways. St. John’s wort changed a CYP3A4 probe drug in human research, creating a reason to check the combination without assuming the size or direction of a clinical zileuton effect.
Different extracts gave different results
A standard St. John’s wort preparation reduced alprazolam exposure, while a low-hyperforin extract had little relevant effect on several probe drugs. These are other-drug studies, not zileuton trials.
Do not substitute a time gap for review
No study defines a spacing interval or a zileuton dose adjustment for this herb. Tell the pharmacist about the precise extract and recent starts or stops; do not alter asthma treatment on your own.
Keep the correct asthma regimen
Zileuton is for ongoing asthma control and does not treat a sudden attack. Follow the instructions for your immediate-release or extended-release product, including its food directions. Do not change the dose to compensate for a supplement.
Continue liver monitoring
Keep the liver blood tests arranged by your prescriber. Promptly report yellow skin or eyes, dark urine, unusual fatigue, nausea or pain in the upper right abdomen. A supplement does not replace the monitoring required during zileuton treatment.
Evidence and practical considerations
Absorption & effectiveness
Current reduced absorption/effectiveness and required timing/avoidance claims are not directly established. CYP induction is a plausible mechanism, but original probe findings and zileuton in vitro metabolic pathways cannot determine net clinical exposure.
- Exact scope
- Hypericum perforatum; extract and hyperforin content affect whether other-drug metabolic findings apply. with Exact zileuton immediate-release and extended-release oral tablets. Exact RxNorm IN40575. Immediate-release and extended-release tablets have different dosing and food instructions; neither is an acute rescue bronchodilator.
- Medication form and route
- oral
- Timing or duration
- Source-specific single-dose, repeated-dose and observational exposures distinguished.
What remains uncertain
- No exact-pair human PK or treatment-failure study identified. Low-hyperforin contrary study prevents universal extract inference; biochemical 5-lipoxygenase inhibition by hyperforin is not evidence of reduced zileuton absorption.
Factors that may matter: preparation and plant part; clinical indication; dose; other medicines; baseline alertness.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed zileuton.
Liver injury precautions and scheduled ALT monitoring; original theophylline interaction study shows reduced clearance, not direct caffeine evidence. CYP1A2, CYP2C9 and CYP3A4 contribute to in vitro metabolism.
How this applies: Exact RxNorm IN40575. Immediate-release and extended-release tablets have different dosing and food instructions; neither is an acute rescue bronchodilator.
No universal supplement dose, interval, event rate or untested formulation equivalence.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed zileuton.
Liver injury precautions and scheduled ALT monitoring; original theophylline interaction study shows reduced clearance, not direct caffeine evidence. CYP1A2, CYP2C9 and CYP3A4 contribute to in vitro metabolism.
How this applies: Exact RxNorm IN40575. Immediate-release and extended-release tablets have different dosing and food instructions; neither is an acute rescue bronchodilator.
No universal supplement dose, interval, event rate or untested formulation equivalence.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Twelve healthy volunteers in an open-label fixed-order crossover.
Alprazolam exposure fell about one-half and clearance increased; elimination half-life shortened.
How this applies: Only the studied preparation, route and measured endpoints apply; no untested respiratory medication transfer.
Single extract, healthy volunteers and no zileuton exposure. CYP3A4 probe result does not establish the net change across zileuton metabolic pathways or reduced gut absorption.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Healthy participants in randomized placebo-controlled studies.
Changes in probe exposures were small and judged clinically irrelevant; hyperforin levels were below quantification.
How this applies: Only the studied preparation, route and measured endpoints apply; no untested respiratory medication transfer.
Preparation-specific result, not permission to assume all retail products are low-hyperforin or all doses safe.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Research summary published | |
| Article prepared | |
| Current exact available claims adjudicated using original captures and explicit identity and comparator limits. |
Article revision: 31a4cf39bd90bb68
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.