Drug & supplement interaction

Ilex Guayusa + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

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

Ilex Guayusa has a minor interaction with Amitriptyline, Perphenazine. Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.

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

Ilex Guayusa and Amitriptyline, Perphenazine

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

Minor

PHENOTHIAZINES

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under PHENOTHIAZINES — the group Ilex Guayusa interacts with.

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Ilex guayusa contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2).
Severity Minor 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

Here's the gist with this one: your combo pill contains perphenazine, a phenothiazine, and that part can slow down a liver enzyme (CYP1A2) that normally breaks down caffeine. Since guayusa is basically a caffeine source, the caffeine may stick around a little longer than usual. So the interaction works on the caffeine side, not the medication. You might notice extra jitteriness, a racing heart, trouble sleeping, or feeling wired.

The good news is this is rated minor and only based on lab-style evidence, so it's more theoretical than something most people actually feel. Still, if you notice that your usual cup hits harder than it used to, ease back on the guayusa and chat with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  2. Daniel, W. A., Syrek, M., Rylko, Z., and Kot, M. Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. Pol.J Pharmacol 2001;53(6):615-621.

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, 470 moderate, 126 minor known drug interactions in our database — the Amitriptyline, Perphenazine one above is one of them. If you take anything else, check it against the full list below.

Major 8 Moderate 470 Minor 126 No known interaction 2,226 (incl. Amitriptyline, Perphenazine)
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 Amitriptyline, Perphenazine

This page covers Ilex Guayusa only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine interaction page

How much people look this up

Where Ilex Guayusa and Amitriptyline, Perphenazine 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

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,040 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
470Moderate
126Minor
2,225No known interaction
8 Major 470 Moderate 126 Minor 2,225 No interaction
Major

8 interactions

Moderate

470 interactions

Showing 60 of 470 moderate interactions — see all 470 on the Ilex Guayusa page.

Minor

126 interactions

Showing 60 of 126 minor interactions — see all 126 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 Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine Together: Common Questions

Can you take Ilex Guayusa with Amitriptyline, Perphenazine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Ilex Guayusa and Amitriptyline, Perphenazine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About Amitriptyline, Perphenazine 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.