Drug & supplement interaction

Caffeine + Promethazine

Promethazine brand name: Phenergan.

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

Caffeine 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

Caffeine 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 Caffeine interacts with.

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Phenothiazines, including perazine, chlorpromazine, levomepromazine, and thioridazine, 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 promethazine (Phenergan) and caffeine: this isn't really about promethazine building up. It's the other way around. Phenothiazines like promethazine may slow down a liver enzyme called CYP1A2, which is what clears caffeine out of your system. So in theory, your morning coffee could hang around a bit longer than usual.

If that happens, you might notice more of the usual caffeine effects: feeling jittery, a faster heartbeat, or trouble sleeping. I'll be honest though, this is only suggested by lab and animal studies, so it's theoretical and pretty minor. Most people won't feel a thing. If you're sensitive to caffeine, just go a little easier and ask your pharmacist if you have concerns.

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

Caffeine Also Interacts With Other Medications

Caffeine has 8 major, 483 moderate, 163 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 483 Minor 163 No known interaction 2,176 (incl. Promethazine)
Taking anything else?

Check Another of Your Medications Against Caffeine

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

From our Q&A

Questions About Caffeine 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 Caffeine 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 Caffeine 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 Caffeine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 6,775 real supplement products containing Caffeine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Caffeine. Your product may carry other ingredients that interact with Promethazine too, on top of Caffeine — 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 Caffeine 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 Caffeine
Top 5%

#25 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 Caffeine

What is Caffeine?

  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Read the full Caffeine 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 & Caffeine

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

8Major
483Moderate
163Minor
2,175No known interaction
8 Major 483 Moderate 163 Minor 2,175 No interaction
Major

8 interactions

Moderate

483 interactions

Showing 60 of 483 moderate interactions — see all 483 on the Caffeine page.

Minor

163 interactions

Showing 60 of 163 minor interactions — see all 163 on the Caffeine page.

No interaction 2,175 drugs checked — show the list

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

Showing the 60 most looked-up of 2,175 medications checked with no known interaction — see the full Caffeine list.

See the full Caffeine 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
Caffeine 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 Caffeine and Promethazine Together: Common Questions

Can you take Caffeine 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 Caffeine 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 Caffeine?

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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.