Drug & supplement interaction

Phenpromethamine + Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine brand names: Gesic C8, Gesic C15, Lenoltec 2, Gesic C30, Lenoltec 3, and others.

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

Phenpromethamine has a moderate interaction with Acetaminophen, Caffeine, Codeine. Theoretically, taking phenpromethamine with stimulant drugs might have additive effects and increase the risk of adverse cardiovascular effects.

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

Phenpromethamine and Acetaminophen, Caffeine, Codeine

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

Moderate

STIMULANT DRUGS

Why this applies to Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine falls under STIMULANT DRUGS — the group Phenpromethamine interacts with.

Theoretically, taking phenpromethamine with stimulant drugs might have additive effects and increase the risk of adverse cardiovascular effects.
Phenpromethamine is a sympathomimetic compound with stimulant properties.
Severity Moderate 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 combination pill mixes acetaminophen (a pain reliever) with codeine (an opioid) and a small dose of caffeine. The caffeine part is the piece that matters here. Caffeine is a mild stimulant, and phenpromethamine is a much stronger amphetamine-like stimulant. Stacking two stimulants together can add up, and in theory that could push your heart rate and blood pressure higher, leaving you feeling jittery, anxious, or with a racing or pounding heartbeat.

To be clear, this concern is theoretical and based on how these compounds behave, not on solid human studies. Honestly, the bigger issue is the phenpromethamine itself, since it is not an approved or legitimate supplement ingredient. I'd steer clear of any product listing it, and check with your pharmacist or doctor before combining anything with this codeine product.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Cohen PA, Travis JC, Vanhee C, Ohana D, Venhuis BJ. Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3-dimethylamylamine (1,3-DMA

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

Phenpromethamine Also Interacts With Other Medications

Phenpromethamine has 171 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Codeine one above is one of them. If you take anything else, check it against the full list below.

Moderate 171 No known interaction 2,659 (incl. Acetaminophen, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Phenpromethamine

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Codeine

This page covers Phenpromethamine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine page lists 303 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), Asarabacca (major), Beer (major) and Ephedra (major).

By severity: 15 major · 244 moderate · 44 minor.

Open the Acetaminophen, Caffeine, Codeine interaction page

How much people look this up

Where Phenpromethamine and Acetaminophen, Caffeine, Codeine 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 Phenpromethamine
Steady interest

#1,118 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Caffeine, Codeine
Top 5%

#83 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 Phenpromethamine

What is Phenpromethamine?

  • Nasal decongestion (historical)
  • Stimulant effects (misuse)
  • Pre-workout 'energy' (illegally added to some products)

Phenpromethamine is a synthetic stimulant drug, not a herb or legitimate dietary supplement. It has been found illegally added to some sports and weight-loss supplements, and it is not approved for use in the United States. You should avoid any product that lists it as an ingredient and talk to a pharmacist or doctor.

Read the full Phenpromethamine monograph & all interactions
Keep checking

Other Drugs & Phenpromethamine

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

0Major
171Moderate
0Minor
2,658No known interaction
171 Moderate 2,658 No interaction
Moderate

171 interactions

Showing 60 of 171 moderate interactions — see all 171 on the Phenpromethamine page.

No interaction 2,658 drugs checked — show the list

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

Showing the 60 most looked-up of 2,658 medications checked with no known interaction — see the full Phenpromethamine list.

See the full Phenpromethamine interactions page
See every supplement checked against Acetaminophen, Caffeine, Codeine, 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
Phenpromethamine monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Codeine, 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 Phenpromethamine and Acetaminophen, Caffeine, Codeine Together: Common Questions

Can you take Phenpromethamine with Acetaminophen, Caffeine, Codeine?
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.
How serious is the Phenpromethamine and Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine and Phenpromethamine?

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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.