Drug & supplement interaction

Ilex Guayusa + Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital brand name: Phenaphen.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Aspirin, Codeine Phosphate, Phenobarbital falls into 2 drug categories that Ilex Guayusa can interact with; the most serious is rated moderate. Theoretically, Ilex guayusa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Read the full interaction report
SeverityModerate
LikelihoodUnlikely
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ilex Guayusa and Aspirin, Codeine Phosphate, Phenobarbital

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Ilex Guayusa interacts with whole categories of medication. Aspirin, Codeine Phosphate, Phenobarbital falls into 2 of those categories, so it can interact with Ilex Guayusa in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 2

Why this applies to Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Ilex Guayusa interacts with.

Theoretically, Ilex guayusa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Ilex guayusa contains caffeine. Caffeine is reported to have antiplatelet activity. Theoretically, caffeine in Ilex guayusa might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood.
Severity Moderate Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combination product contains aspirin, which is the piece that matters here. Aspirin already thins your blood and keeps platelets from clumping together, which is how it prevents clots. Guayusa is mostly caffeine, and caffeine is thought to have a mild blood-thinning, anti-platelet effect of its own. So on paper, sipping guayusa alongside your aspirin could add a little to that thinning effect.

The honest truth is that this concern is theoretical. It comes from how caffeine behaves in the lab, not from real reports in people, so it's unlikely to cause trouble. Still, if you ever notice easy bruising, nosebleeds, or bleeding gums, or you drink a lot of guayusa, mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Ali M, Afzal M. A potent inhibitor of thrombin stimulated platelet thromboxane formation from unprocessed tea. Prostaglandins Leukot Med 1987;27:9-13. PubMed
  2. Ardlie NG, Glew G, Schultz BG, Schwartz CJ. Inhibition and reversal of platelet aggregation by methyl xanthines. Thromb Diath Haemorrh 1967;18:670-3. DOI
  3. Samarrae WA, Truswell AS. Short-term effect of coffee on blood fibrinolytic activity in healthy adults. Atherosclerosis 1977;26:255-60. PubMed
Moderate

PHENOBARBITAL (Luminal)

2 of 2
Theoretically, Ilex guayusa might reduce the effects of phenobarbital and increase the risk for convulsions.
Ilex guayusa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. The exact mechanism of this interaction is unclear.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

The piece of your combination pill I want to focus on is the phenobarbital, which is a barbiturate used to calm the nervous system and help prevent seizures. The caffeine naturally found in guayusa works in the opposite direction, acting as a stimulant that wakes the brain up. Because of that push and pull, there's a theory that regularly drinking strong guayusa could chip away at how well phenobarbital controls seizures, possibly raising the risk of a breakthrough convulsion.

Honestly, this concern comes from animal studies only, so it's more theoretical than proven, and the exact mechanism isn't clear. An occasional cup is unlikely to be a big deal, but heavy or daily use is worth a quick chat with your pharmacist or doctor before you make it a habit.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gasior, M., Borowicz, K., Buszewicz, G., Kleinrok, Z., and Czuczwar, S. J. Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia 1996;37(3 PubMed
  2. Jankiewicz, K., Chroscinska-Krawczyk, M., Blaszczyk, B., and Czuczwar, S. J. [Caffeine and antiepileptic drugs: experimental and clinical data]. Przegl.Lek. 2007;64(11):965-967.
  3. Chroscinska-Krawczyk, M., Jargiello-Baszak, M., Walek, M., Tylus, B., and Czuczwar, S. J. Caffeine and the anticonvulsant potency of antiepileptic drugs: experimental and clinical data. Pharmacol.Rep. 2011;63(1):12-18. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Ilex Guayusa Also Interacts With Other Medications

Ilex Guayusa has 8 major, 469 moderate, 127 minor known drug interactions in our database — the Aspirin, Codeine Phosphate, Phenobarbital one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 469 Minor 127 No known interaction 2,226 (incl. Aspirin, Codeine Phosphate, Phenobarbital)
Taking anything else?

Check Another of Your Medications Against Ilex Guayusa

Covers the 2,830 medications we’ve checked against Ilex Guayusa. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Aspirin, Codeine Phosphate, Phenobarbital

This page covers Ilex Guayusa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Codeine Phosphate, Phenobarbital page lists 352 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 12 major · 304 moderate · 36 minor.

From our pharmacist’s overview on the Aspirin, Codeine Phosphate, Phenobarbital page

“Alcohol is the entry I would flag first with Phenaphen (aspirin, codeine phosphate, phenobarbital): beer or wine layered onto codeine and phenobarbital can deepen sedation and, at worst, slow breathing. This medication deserves real caution with supplements.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Codeine Phosphate, Phenobarbital interaction page

How much people look this up

Where Ilex Guayusa and Aspirin, Codeine Phosphate, Phenobarbital Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Ilex Guayusa
Steady interest

#990 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Aspirin, Codeine Phosphate, Phenobarbital
Steady interest

#1,590 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Ilex Guayusa

What is Ilex Guayusa?

  • Energy and alertness
  • Mental focus
  • Antioxidant support
  • Appetite control
  • Athletic and physical performance

Ilex guayusa is a caffeine-containing holly leaf from the Amazon, traditionally brewed as a tea for energy and alertness, much like yerba mate or green tea. There is limited human research confirming specific health benefits, and its main reliable effect comes from its caffeine content. Because it is a stimulant, use it cautiously and check with your pharmacist or doctor if you have heart concerns or are pregnant.

Read the full Ilex Guayusa monograph & all interactions
Keep checking

Other Drugs & Ilex Guayusa

Browse every other medication we’ve checked against Ilex Guayusa — both the ones with a known interaction and the ones without. Select any drug for the full detail.

8Major
469Moderate
127Minor
2,225No known interaction
8 Major 469 Moderate 127 Minor 2,225 No interaction
Major

8 interactions

Moderate

469 interactions

Showing 60 of 469 moderate interactions — see all 469 on the Ilex Guayusa page.

Minor

127 interactions

Showing 60 of 127 minor interactions — see all 127 on the Ilex Guayusa page.

No interaction 2,225 drugs checked — show the list

We also checked Ilex Guayusa against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,225 medications checked with no known interaction — see the full Ilex Guayusa list.

See the full Ilex Guayusa interactions page
See every supplement checked against Aspirin, Codeine Phosphate, Phenobarbital, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Ilex Guayusa monograph › Uses, safety, and every drug interaction in one place Aspirin, Codeine Phosphate, Phenobarbital supplement interactions › Every supplement checked against Aspirin, Codeine Phosphate, Phenobarbital, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Ilex Guayusa and Aspirin, Codeine Phosphate, Phenobarbital Together: Common Questions

Can you take Ilex Guayusa with Aspirin, Codeine Phosphate, Phenobarbital?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Ilex Guayusa and Aspirin, Codeine Phosphate, Phenobarbital?
Aspirin, Codeine Phosphate, Phenobarbital belongs to more than one drug category, and Ilex Guayusa interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Ilex Guayusa and Aspirin, Codeine Phosphate, Phenobarbital interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Aspirin, Codeine Phosphate, Phenobarbital and Ilex Guayusa?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.