Drug & supplement interaction

Coffee + Amitriptyline, Perphenazine

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

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

Amitriptyline, Perphenazine falls into 2 drug categories that Coffee can interact with; the most serious is rated minor. Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.

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

Coffee and Amitriptyline, Perphenazine

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

Why Are There 2 Interactions?

Coffee interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 2 of those categories, so it can interact with Coffee in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

PHENOTHIAZINES

1 of 2

Why this applies to Amitriptyline, Perphenazine

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

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine. Also, coffee may bind to phenothiazines and reduce their absorption.
Coffee contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2). Additionally, the tannins in coffee may bind to phenothiazines in the gastrointestinal tract and reduce their absorption.
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

This combo pill pairs amitriptyline (an antidepressant) with perphenazine (a phenothiazine). The interaction on file points two directions, but both are theoretical and rated minor. First, perphenazine can slow how your body clears caffeine, so your usual cups of coffee may hit a bit harder, think extra jitters, a racing heart, or trouble sleeping. Second, the tannins in coffee can latch onto perphenazine in your stomach, which could slightly lower how much medicine gets absorbed.

Honestly, this is based on lab data, not real patient reports, so for most folks a normal coffee habit won't cause problems. To be safe, try not to swallow your dose with a mug of coffee, and chat with your pharmacist if you notice more jitteriness than usual.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. PubMed
  2. Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130.
  3. 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
  4. 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.
Minor

TRICYCLIC ANTIDEPRESSANTS (TCAs)

2 of 2

Amitriptyline, Perphenazine also falls under TRICYCLIC ANTIDEPRESSANTS (TCAs).

Theoretically, TCAs might bind with coffee constituents when taken at the same time.
In vitro research suggests that the tannins in coffee might cause precipitation of TCAs. However, this effect has not been reported in humans.
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 Triavil (which combines amitriptyline, a tricyclic antidepressant, with perphenazine): in a lab dish, the tannins in coffee can grab onto the amitriptyline part and make it clump together. In theory, that could mean a little less of the drug gets absorbed if you wash your pills down with coffee at the very same moment.

But I want to be honest about how soft this evidence is. This has only been seen in test tubes, never reported in real people, and it's rated a minor interaction. I wouldn't lose sleep over it. If you'd like to play it safe, just take your dose with water and enjoy your coffee separately. Any questions, your pharmacist is happy to help.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricylic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984;73:1056-8. PubMed
  2. Kulhanek F, Linde OK, Meisenberg G. Precipitation of antipsychotic drugs in interaction with coffee or tea. Lancet 1979;2:1130.

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

Coffee Also Interacts With Other Medications

Coffee has 8 major, 467 moderate, 115 minor known drug interactions in our database — the Amitriptyline, Perphenazine one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 467 Minor 115 No known interaction 2,240 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against Coffee

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

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Perphenazine

This page covers Coffee 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 Coffee as Part of a Dietary Supplement Product? Check It for Interactions

We hold 716 real supplement products containing Coffee, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Coffee. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Coffee — 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 Coffee 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 Coffee
Top 5%

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,336 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 Coffee

What is Coffee?

  • Alertness and reducing fatigue
  • Mental focus and concentration
  • Athletic performance
  • Headache relief
  • Weight management

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healthy adults, moderate coffee intake is generally safe and may have some health benefits, but too much can cause jitteriness, poor sleep, and a faster heartbeat. People who are pregnant, breastfeeding, or sensitive to caffeine should limit their intake and check with a doctor or pharmacist.

Read the full Coffee monograph & all interactions
Keep checking

Other Drugs & Coffee

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

8Major
467Moderate
115Minor
2,239No known interaction
8 Major 467 Moderate 115 Minor 2,239 No interaction
Major

8 interactions

Moderate

467 interactions

Showing 60 of 467 moderate interactions — see all 467 on the Coffee page.

Minor

115 interactions

Showing 60 of 115 minor interactions — see all 115 on the Coffee page.

No interaction 2,239 drugs checked — show the list

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

Showing the 60 most looked-up of 2,239 medications checked with no known interaction — see the full Coffee list.

See the full Coffee 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
Coffee 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 Coffee and Amitriptyline, Perphenazine Together: Common Questions

Can you take Coffee 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.
Why are there 2 interactions listed for Coffee and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and Coffee 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 Coffee 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 Coffee?

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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.