Drug & supplement interaction

Guarana + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.

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

Guarana has a moderate interaction with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine. Theoretically, concomitant use might increase stimulant adverse effects.

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

Guarana and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Moderate

STIMULANT DRUGS

Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under STIMULANT DRUGS — the group Guarana interacts with.

Theoretically, concomitant use might increase stimulant adverse effects.
Guarana 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 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 thing about this combination product (Hycomine Compound): it already contains caffeine in the formula. Guarana is basically concentrated caffeine too, so adding it on top means you're stacking two caffeine sources. That can pile up faster than people expect.

When the caffeine adds up, you may notice more jitteriness, a racing or pounding heart, trouble sleeping, anxiety, or shakiness. The phenylephrine in this product can also nudge your heart rate and blood pressure up, so the stimulant effects may feel stronger together. This concern is mostly theoretical, based on how caffeine works rather than firm studies, so it's not an emergency. Still, if you take this medicine regularly, it's worth a quick chat with your pharmacist or doctor before adding a guarana supplement.

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

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, 461 moderate, 185 minor known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is one of them. If you take anything else, check it against the full list below.

Major 8 Moderate 461 Minor 185 No known interaction 2,176 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
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.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Guarana only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page

“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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%

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

29 days ago today
Medication Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Top 25%

#467 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
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
461Moderate
185Minor
2,175No known interaction
8 Major 461 Moderate 185 Minor 2,175 No interaction
Major

8 interactions

Moderate

461 interactions

Showing 60 of 461 moderate interactions — see all 461 on the Guarana page.

Minor

185 interactions

Showing 60 of 185 minor interactions — see all 185 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine, 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 Guarana and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions

Can you take Guarana with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
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 Guarana and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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, Chlorpheniramine, Hydrocodone, Phenylephrine 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.