The short answer
A specific harmful interaction between guarana and zileuton has not been demonstrated. Review substantial caffeine intake, but do not treat theophylline research as proof for this product.
What this answer covers
Paullinia cupana seed products; caffeine amounts and mixtures vary.
- Supplement or preparation
- Paullinia cupana
- Medication ingredient
- zileuton
The direct study involved another drug
Zileuton raised theophylline concentrations and adverse effects in a controlled human study. Theophylline is a prescription medicine; this result cannot tell us how much caffeine or a botanical product is affected.
Review the actual exposure
Check the seed or extract preparation and caffeine amount. Guarana cardiovascular precautions remain relevant on their own, but do not prove that zileuton increases them.
What timing can and cannot do
The reviewed evidence does not establish an absorption problem or a tested clock gap for this pair. Ask the pharmacist for a product-specific plan rather than separating doses by an invented number of hours.
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
Side effects & toxicity
The current pair-specific increased toxicity claim remains insufficiently established. Zileuton reduced theophylline clearance in an original trial, but caffeine or a caffeine-containing botanical was not studied. Routine separation or blanket avoidance is unproven.
- Exact scope
- Paullinia cupana seed products; caffeine amounts and mixtures vary. 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 original clinical study identified. Shared methylxanthine metabolism gives a hypothesis, not a measured exposure change, clinical event rate or safe interval.
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
ema.europa.eu · Source check Sep 10, 2026
Population: People considering the specified supplement.
HMPC assesses oral dried powdered guarana seeds for traditional fatigue use; cardiovascular contraindications apply to specified seed medicines.
How this applies: Supplement-only context; explicit medication and preparation bridge required.
Not proof of exact-drug combination risk or equivalence to caffeine capsules or multi-ingredient energy products.
Source 4: official supplement guidance
fda.gov · Source check Sep 10, 2026
Population: People considering the specified supplement.
Caffeine can cause palpitations, anxiety, sleep problems and other effects; sensitivity depends partly on medicines and individual factors.
How this applies: Supplement-only context; explicit medication and preparation bridge required.
General adult intake advice does not establish a safe caffeine limit with this medicine.
Source 5: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Sixteen healthy men in placebo-controlled crossover.
Theophylline clearance fell and concentrations rose; adverse events were more frequent with zileuton co-use.
How this applies: Only the named drug, preparation, route and measured endpoints apply.
A direct drug-drug study, not caffeine, tea, guarana or cola seed; cannot transfer measured changes to another methylxanthine.
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: 9565613958ebd250
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.