Drug & supplement interaction

Ilex Guayusa + Clozapine

Clozapine brand names: Clozaril, Versacloz.

Moderate Interaction
The bottom line Moderate

Ilex Guayusa has a moderate interaction with Clozapine. Theoretically, Ilex guayusa might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ilex Guayusa and Clozapine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CLOZAPINE (Clozaril)

Theoretically, Ilex guayusa might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Ilex guayusa contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine.
Severity Moderate Likelihood Possible Evidence B

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

Here's the deal with guayusa and your clozapine. Guayusa is basically a caffeine source, much like a strong tea. Clozapine is cleared from your body by a liver enzyme called CYP1A2, and the caffeine in guayusa may slow that enzyme down a bit. If clozapine clears more slowly, its levels can creep up, which could mean more side effects like heavy drowsiness, dizziness, drooling, a racing heartbeat, or constipation.

I want to be honest, though: this is mostly theoretical, and the evidence that caffeine truly blocks this enzyme is weak. An occasional cup probably won't cause trouble, but large or daily amounts might matter more. Since clozapine needs careful monitoring, please run guayusa past your pharmacist or prescriber before adding it.

References
  1. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  2. Raaska K, Raitasuo V, Laitila J, Neuvonen PJ. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Basic Clin Pharmacol Toxicol 2004;94:13-8. DOI

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 Clozapine one above is one of them. If you take anything else, check it against the full list below.

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.

From our Q&A

Questions About Ilex Guayusa or Clozapine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Ilex Guayusa or Clozapine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Clozapine

This page covers Ilex Guayusa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Clozapine page lists 212 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Indian Snakeroot (major), Lithium (major) and Rauvolfia Vomitoria (major).

By severity: 6 major · 164 moderate · 42 minor.

From our pharmacist’s overview on the Clozapine page

“Clozapine (Clozaril, Versacloz) is usually the last-resort antipsychotic for schizophrenia, prescribed under close monitoring because small shifts in its blood level matter, so the 212 supplement interactions on file here deserve genuine care rather than a quick skim. Six are rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Clozapine interaction page

How much people look this up

Where Ilex Guayusa and Clozapine 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

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

29 days ago today
Medication Clozapine
Steady interest

#1,709 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
Medication

About Clozapine

What Is Clozapine Used For?

Brand names: Clozaril, Versacloz

Clozapine is used for two specific situations. First, it is prescribed for people with severe schizophrenia who have already tried other antipsychotic medications and have not gotten adequate relief. It is reserved for this group because of its serious risks.

Second, clozapine is used to lower the chances of repeated suicidal behavior in people with schizophrenia or schizoaffective disorder who are considered to be at ongoing, chronic risk. It is not a first-choice medication — it is used when the need is serious and other options have fallen short.

See full Clozapine drug information
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
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
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

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Pharmacist Counseling Corner

Taking Ilex Guayusa and Clozapine Together: Common Questions

Can you take Ilex Guayusa with Clozapine?
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.
How serious is the Ilex Guayusa and Clozapine 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 Clozapine 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.