The short answer
Avoid starting kava without the zileuton prescriber’s review because both have liver safety concerns. The combined injury rate has not been measured.
What this answer covers
Piper methysticum; aqueous beverages and different solvent extracts are not identical exposures, and no preparation is proven safe with zileuton.
- Supplement or preparation
- Piper methysticum
- Medication ingredient
- zileuton
Why liver safety is the main concern
Zileuton can cause liver injury and requires blood tests. Kava preparations have also been linked to rare serious liver injury. Combining these concerns warrants prescriber review even though the exact pair has not been tested.
Preparation does not settle safety
Early reports involved solvent extracts, but water-prepared kava beverages have also been reported. In an observational study, heavy traditional beverage use was associated with elevated GGT, a liver-related marker; this was not proof of liver failure or a zileuton interaction.
The enzyme study was limited
A small healthy-volunteer study found no significant kava effect on CYP1A2 or CYP3A4 probe measures. That argues against assuming broad enzyme inhibition, but does not demonstrate safety with zileuton or rule out uncommon liver injury.
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.
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.
Evidence and practical considerations
Side effects & toxicity
Conditional liver-injury concern is supported by the exact zileuton warning and independent kava liver evidence. Direct synergistic injury or a raised zileuton concentration has not been demonstrated.
- Exact scope
- Piper methysticum; aqueous beverages and different solvent extracts are not identical exposures, and no preparation is proven safe with zileuton. 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 study. Traditional-beverage GGT elevation is not clinical liver failure, and null CYP1A2/3A4 probe results do not exclude rare injury. No spacing solution or safe kava dose established.
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: official supplement guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: People considering the specified supplement.
Rare serious liver injury has been reported with various kava preparations, including aqueous beverages.
How this applies: Supplement-only context; explicit medication and preparation bridge required.
No exact zileuton co-use or proven combined injury rate; formulation and coexposures vary.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Thirty-one healthy adult kava drinkers and thirty-one non-drinkers in Hawaii.
Heavy beverage consumption associated with elevated GGT.
How this applies: Only the named drug, preparation, route and measured endpoints apply.
Observational marker association, not proof of clinical liver failure; no zileuton co-use or equivalence to all extracts.
Source 5: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Twelve healthy volunteers.
Kava inhibited CYP2E1; no significant CYP1A2 or CYP3A4/5 change detected.
How this applies: Only the named drug, preparation, route and measured endpoints apply.
Probe measures, one extract and no zileuton; null probe results cannot exclude rare liver injury.
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: fae26b4e2ca1f0bc
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.