Drug & supplement interaction

Coffee + Promethazine, Pseudoephedrine

Promethazine, Pseudoephedrine brand name: Phenergan D.

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

Promethazine, Pseudoephedrine falls into 2 drug categories that Coffee can interact with; the most serious is rated moderate. Theoretically, concomitant use might increase stimulant adverse effects.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceC
What do Severity, Likelihood & Evidence mean?
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Interaction report

Coffee and Promethazine, Pseudoephedrine

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. Promethazine, Pseudoephedrine 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 (Moderate).

Moderate

STIMULANT DRUGS

1 of 2

Why this applies to Promethazine, Pseudoephedrine

Promethazine, Pseudoephedrine falls under STIMULANT DRUGS — the group Coffee interacts with.

Theoretically, concomitant use might increase stimulant adverse effects.
Coffee contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects.
Severity Moderate Likelihood Probable Evidence C

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combo product pairs pseudoephedrine, a decongestant that gently stimulates your system, with promethazine, an antihistamine that often makes you drowsy. The piece that matters here is the pseudoephedrine. Coffee's caffeine is also a stimulant, so drinking a lot on top of this medicine can stack those effects. You might notice a racing or pounding heartbeat, jitteriness, anxiety, higher blood pressure, or trouble sleeping.

This is more of a theoretical, common-sense caution than a proven, dangerous interaction, and a normal cup or two of coffee is usually fine for most people. If you feel wired, shaky, or your heart is fluttering, ease off the caffeine and check in with your pharmacist or doctor, especially if you have heart issues or high blood pressure.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Institute of Medicine. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington, DC: National Academy Press, 2001. Available at: http://books.nap.edu/books/0309082587/html/index.html. DOI
Minor

PHENOTHIAZINES

2 of 2

Promethazine, Pseudoephedrine also falls under PHENOTHIAZINES.

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 deal with your Phenergan D and your morning cup of coffee. There are two small, mostly theoretical things going on. First, the promethazine part can slow how your body clears caffeine, so the caffeine may hang around a little longer than usual. That could mean more jitters, a racing heart, or trouble winding down to sleep, which is worth noting since pseudoephedrine already tends to be a bit stimulating on its own.

Second, compounds in coffee may bind to promethazine in your gut and slightly lower how much you absorb. Honestly, this is based on lab data, not real-world patient reports, and it's rated minor. Most people do fine. If you notice extra restlessness or a pounding heart, just space them out and check with your pharmacist.

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, 466 moderate, 116 minor known drug interactions in our database — the Promethazine, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 466 Minor 116 No known interaction 2,240 (incl. Promethazine, Pseudoephedrine)
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 Promethazine, Pseudoephedrine

This page covers Coffee only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Promethazine, Pseudoephedrine page lists 116 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Henbane (major), Peyote (major) and Rauvolfia Vomitoria (major).

By severity: 7 major · 93 moderate · 16 minor.

From our pharmacist’s overview on the Promethazine, Pseudoephedrine page

“Phenergan D combines a sedating antihistamine, promethazine, with the decongestant stimulant pseudoephedrine, and its supplement list pulls hard in both directions, so this is one to treat with genuine care. The biggest cluster, from everyday caffeine sources like coffee and cola nut up to ephedra, stacks extra stimulation on the pseud…”

Reviewed by 2 · Jul 18, 2026

Open the Promethazine, Pseudoephedrine 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, Pseudoephedrine 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, Pseudoephedrine 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, Pseudoephedrine
Steady interest

#1,785 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
466Moderate
116Minor
2,239No known interaction
8 Major 466 Moderate 116 Minor 2,239 No interaction
Major

8 interactions

Moderate

466 interactions

Showing 60 of 466 moderate interactions — see all 466 on the Coffee page.

Minor

116 interactions

Showing 60 of 116 minor interactions — see all 116 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, Pseudoephedrine, 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, Pseudoephedrine supplement interactions › Every supplement checked against Promethazine, Pseudoephedrine, 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 Promethazine, Pseudoephedrine Together: Common Questions

Can you take Coffee with Promethazine, Pseudoephedrine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Coffee and Promethazine, Pseudoephedrine?
Promethazine, Pseudoephedrine 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 Promethazine, Pseudoephedrine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Promethazine, Pseudoephedrine 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.