Drug & supplement interaction

Guarana + Promethazine

Promethazine brand name: Phenergan.

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

Guarana 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

Guarana 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 Guarana interacts with.

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Guarana 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 guarana and promethazine (Phenergan): guarana is basically a concentrated source of caffeine. Promethazine can mildly slow down the liver enzyme (CYP1A2) that clears caffeine out of your body. So in theory, the caffeine from guarana might hang around a bit longer and feel a little stronger, meaning more jitters, a faster heartbeat, restlessness, or trouble sleeping.

I want to be honest about the evidence here: this is a theoretical concern based on lab studies, not real-world reports, and it's rated minor. There's also a funny tension, since promethazine itself tends to make you sleepy, while caffeine fights that. A normal cup of coffee likely won't matter much, but high-dose guarana supplements could. If you take both regularly, just run it by your pharmacist or doctor.

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

Guarana Also Interacts With Other Medications

Guarana has 8 major, 462 moderate, 184 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 462 Minor 184 No known interaction 2,176 (incl. Promethazine)
Taking anything else?

Check Another of Your Medications Against Guarana

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

From our Q&A

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

We hold 1,430 real supplement products containing Guarana, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Guarana. Your product may carry other ingredients that interact with Promethazine too, on top of Guarana — 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 Guarana 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 Guarana
Top 10%

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

29 days ago today
Medication Promethazine
Top half

#815 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 Guarana

What is Guarana?

Guarana
  • Energy and alertness
  • Reducing fatigue
  • Weight loss support
  • Athletic performance
  • Mental focus

Guarana is an Amazonian seed that is naturally high in caffeine, which explains most of its stimulant and energy effects. While it may give a short-term boost in alertness and reduce fatigue, strong evidence for weight loss or major performance gains is limited, and it carries the same risks as too much caffeine. Talk to your pharmacist or doctor before using it, especially if you have heart problems, anxiety, or are pregnant.

Read the full Guarana 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 & Guarana

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

8Major
462Moderate
184Minor
2,175No known interaction
8 Major 462 Moderate 184 Minor 2,175 No interaction
Major

8 interactions

Moderate

462 interactions

Showing 60 of 462 moderate interactions — see all 462 on the Guarana page.

Minor

184 interactions

Showing 60 of 184 minor interactions — see all 184 on the Guarana page.

No interaction 2,175 drugs checked — show the list

We also checked Guarana 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 Guarana list.

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

Can you take Guarana 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 Guarana 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 Guarana?

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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.