Drug & supplement interaction

Coffee + Promethazine

Promethazine brand name: Phenergan.

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

Coffee has a minor interaction with Promethazine. 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

Coffee and Promethazine

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

Minor

PHENOTHIAZINES

Why this applies to Promethazine

Promethazine 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

Here's the short version on mixing your morning coffee with promethazine (Phenergan). There are two small things going on, and neither is a big deal for most folks. First, promethazine can slightly slow down how your body clears caffeine, so a cup of coffee might hit you a touch harder than usual. You may feel a bit more wired, restless, or have trouble settling down, though that can feel a little odd alongside the drowsiness promethazine usually causes.

Second, compounds in coffee may bind to promethazine in your stomach and make a little less of it absorb, which could blunt its effect. This is theoretical, based only on lab work, not on strong human studies. If you'd like to play it safe, just space your coffee and your dose apart by an hour or so, and check with your pharmacist if you have questions.

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.

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 Promethazine one above is one of 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. Promethazine)
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.

From our Q&A

Questions About Coffee or Promethazine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Coffee or Promethazine, 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 Promethazine

This page covers Coffee only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Promethazine page lists 83 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Scopolia (major), Alfalfa (moderate) and Angel's Trumpet (moderate).

By severity: 3 major · 57 moderate · 23 minor.

From our pharmacist’s overview on the Promethazine page

“Promethazine (Phenergan) is a phenothiazine antihistamine used for allergies, nausea, and motion sickness, and it is strongly anticholinergic on its own, causing dry mouth, blurred vision, drowsiness, and constipation. That is why the 83 supplements and herbs on this list deserve real attention, starting with the three rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Promethazine 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 Promethazine 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 Promethazine 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 Promethazine
Top half

#824 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
Medication

About Promethazine

What Is Promethazine Used For?

Brand name: Phenergan

Promethazine is used for a wide range of conditions. Tablets, oral solution, and rectal suppositories (brands including Phenergan, Promethegan, and Phenadoz) are approved for seasonal and perennial allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, hives (urticaria), angioedema, dermographism, and allergic reactions to blood or plasma. They are also used for motion sickness (both prevention and active treatment), nausea and vomiting related to anesthesia and surgery, sedation, and as a helper medication alongside pain relievers after surgery.

Promethazine hydrochloride injection (brands including Phenergan and Promethazine HCl injection) is used for many of the same purposes but is reserved for situations where oral treatment is not possible — including allergic emergencies as an adjunct to epinephrine, sedation during labor, and as an aid during certain surgical procedures such as bronchoscopy and eye surgery.

See full Promethazine drug information
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 Promethazine, 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 Promethazine supplement interactions › Every supplement checked against Promethazine, ranked by severity Promethazine drug information › The full plain-English guide to this medication 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 Promethazine Together: Common Questions

Can you take Coffee with Promethazine?
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 Coffee and Promethazine 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 Promethazine 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.