Drug & supplement interaction

Cola Nut + Amitriptyline, Perphenazine

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

Minor Interaction
The bottom line Minor

Cola Nut has a minor interaction with Amitriptyline, Perphenazine. Theoretically, phenothiazines might increase the levels and adverse effects of the caffeine in cola nut.

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

Cola Nut 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 Cola Nut interacts with.

Theoretically, phenothiazines might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut 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 combination product (which pairs amitriptyline with the phenothiazine perphenazine) and cola nut. The perphenazine piece can slow down a liver enzyme called CYP1A2, and that enzyme is one of the main ways your body clears caffeine. Since cola nut is basically a caffeine source, the worry is that the caffeine hangs around longer and hits harder.

In real life that might mean feeling jittery, a racing or pounding heart, trouble sleeping, or feeling on edge. Just keep in mind this is a theoretical, lab-based concern rated as minor, not something proven in people. A cup or two of a cola drink probably won't be a big deal, but concentrated cola nut supplements could stack up. If you notice extra restlessness or palpitations, chat with your pharmacist or doctor.

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

Cola Nut Also Interacts With Other Medications

Cola Nut has 547 moderate, 107 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.

Taking anything else?

Check Another of Your Medications Against Cola Nut

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

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Perphenazine

This page covers Cola Nut 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

One more smart check

Taking Cola Nut as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2 real supplement products containing Cola Nut, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cola Nut. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Cola Nut — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Cola Nut 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 Cola Nut
Steady interest

#1,023 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,154 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 Cola Nut

What is Cola Nut?

Cola Nut
  • Energy and alertness
  • Mental focus
  • Physical performance
  • Weight loss support
  • Traditional digestive aid

Cola nut is a caffeine-containing seed from West Africa used mainly as a natural stimulant for energy and alertness. Most of its effects come from caffeine, and strong human evidence for specific health benefits is limited. Because of its caffeine content, people sensitive to stimulants and those who are pregnant or have heart conditions should be cautious.

Read the full Cola Nut monograph & all interactions
Keep checking

Other Drugs & Cola Nut

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

0Major
547Moderate
107Minor
2,175No known interaction
Moderate

547 interactions

Showing 60 of 547 moderate interactions — see all 547 on the Cola Nut page.

Minor

107 interactions

Showing 60 of 107 minor interactions — see all 107 on the Cola Nut page.

No interaction 2,175 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 Cola Nut and Amitriptyline, Perphenazine Together: Common Questions

Can you take Cola Nut 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 Cola Nut 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

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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.