Drug & supplement interaction

Cola Nut + 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 Cola Nut 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

Cola Nut and Promethazine, Pseudoephedrine

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

Why Are There 2 Interactions?

Cola Nut interacts with whole categories of medication. Promethazine, Pseudoephedrine falls into 2 of those categories, so it can interact with Cola Nut 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 Cola Nut interacts with.

Theoretically, concomitant use might increase stimulant adverse effects.
Cola nut 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

Here's the simple version. Phenergan D pairs an antihistamine (promethazine) with a decongestant called pseudoephedrine. That pseudoephedrine is itself a stimulant. Cola nut brings caffeine to the table, another stimulant. Stack two stimulants together and you can pile on the same kinds of side effects: a racing or pounding heart, jitteriness, feeling wired or anxious, trouble sleeping, and a bump in blood pressure.

This concern is mostly theoretical and based on expert opinion, not strong studies, so it isn't a red-alert situation. Still, if you have high blood pressure, heart issues, or you're sensitive to caffeine, it's worth being thoughtful. A cup of regular coffee is one thing; concentrated cola nut supplements add up faster. Before combining them, check with your pharmacist or doctor.

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 the caffeine in cola nut.
Cola nut contains caffeine. Phenothiazines 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 Phenergan D and cola nut. The promethazine part of this combo can mildly slow down a liver enzyme called CYP1A2, which is the same enzyme your body uses to clear caffeine. Cola nut is basically a natural caffeine source, so in theory that caffeine could hang around a little longer than usual and feel stronger.

What might that look like? More jitteriness, a faster or pounding heartbeat, trouble sleeping, or feeling wired. Keep in mind the pseudoephedrine in this product is already a stimulant on its own, so stacking extra caffeine on top can add to that restless, racing feeling. The good news is this interaction is rated minor and is based only on lab data, not real patient reports, so it's usually not a big deal. Still, if you notice your heart racing, check in with your pharmacist.

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

Cola Nut Also Interacts With Other Medications

Cola Nut has 546 moderate, 108 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.

Moderate 546 Minor 108 No known interaction 2,176 (incl. Promethazine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Cola Nut

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

Everything else you take

See Every Supplement That Interacts With Promethazine, Pseudoephedrine

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

We hold 2 real supplement products containing Cola Nut, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cola Nut. Your product may carry other ingredients that interact with Promethazine, Pseudoephedrine too, on top of Cola Nut — 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 Cola Nut 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 Cola Nut
Steady interest

#1,035 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 Cola Nut

What is Cola Nut?

Cola Nut
  • Energy and alertness
  • Mental focus
  • Physical performance
  • Weight loss support
  • Traditional digestive aid

Cola nut is a caffeine-containing seed from West Africa used mainly as a natural stimulant for energy and alertness. Most of its effects come from caffeine, and strong human evidence for specific health benefits is limited. Because of its caffeine content, people sensitive to stimulants and those who are pregnant or have heart conditions should be cautious.

Read the full Cola Nut monograph & all interactions
Keep checking

Other Drugs & Cola Nut

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

0Major
546Moderate
108Minor
2,175No known interaction
546 Moderate 108 Minor 2,175 No interaction
Moderate

546 interactions

Showing 60 of 546 moderate interactions — see all 546 on the Cola Nut page.

Minor

108 interactions

Showing 60 of 108 minor interactions — see all 108 on the Cola Nut page.

No interaction 2,175 drugs checked — show the list

We also checked Cola Nut 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 Cola Nut list.

See the full Cola Nut 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
Cola Nut 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 Cola Nut and Promethazine, Pseudoephedrine Together: Common Questions

Can you take Cola Nut 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 Cola Nut and Promethazine, Pseudoephedrine?
Promethazine, Pseudoephedrine belongs to more than one drug category, and Cola Nut 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 Cola Nut 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 Cola Nut?

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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.