Drug & supplement interaction

Yerba Mate + 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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 2 drug categories that Yerba Mate can interact with; the most serious is rated moderate. Theoretically, concomitant use of stimulant drugs and yerba mate 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

Yerba Mate and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Why Are There 2 Interactions?

Yerba Mate interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 2 of those categories, so it can interact with Yerba Mate 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Theoretically, concomitant use of stimulant drugs and yerba mate might increase stimulant adverse effects.
Yerba mate contains caffeine. Due to the CNS stimulant effects of the caffeine, concomitant use 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: this combination product (Hycomine Compound) already has caffeine built into it. Yerba mate brings its own caffeine to the table, so drinking it alongside your medicine basically stacks one stimulant on top of another. The bigger the cup and the more you drink, the more it adds up.

What you might feel is more of caffeine's usual jitter: a racing or pounding heart, restlessness, trouble sleeping, an upset stomach, or feeling wired and anxious. The phenylephrine (a decongestant) can nudge blood pressure up too, so the two together may make that worse. This is a theoretical, expert-opinion concern rather than a proven danger, and a small amount of mate is unlikely to cause trouble for most people. Still, if you notice these effects or have heart or blood pressure concerns, check with your pharmacist or doctor before pairing them.

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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, yerba mate might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yerba mate extract inhibits CYP3A4 enzymes. Theoretically, taking yerba mate may increase levels and adverse effects of CYP3A4 substrates.
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 practical picture with Hycomine Compound, which is a combo product that already contains caffeine. Yerba mate brings its own caffeine to the table, so the most realistic, everyday concern isn't really the enzyme stuff, it's stacking caffeine on caffeine. That can leave you jittery, restless, with a racing heart or trouble sleeping.

On the lab side, test-tube research hints that yerba mate might slow the CYP3A4 enzyme that helps clear the hydrocodone piece, which could in theory nudge up sedative effects like drowsiness, dizziness, or slowed breathing. But this is theoretical and based only on lab data, so it's rated minor. If you take this medicine regularly, just check in with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Feltrin C, Farias IV, Sandjo LP, Reginatto FH, Simões CMO. Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes. Chem Res Toxicol 2020;33(9):2408-2419. PubMed

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

Yerba Mate Also Interacts With Other Medications

Yerba Mate has 8 major, 504 moderate, 573 minor known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 504 Minor 573 No known interaction 1,745 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Yerba Mate

Covers the 2,830 medications we’ve checked against Yerba Mate. 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 Yerba Mate 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 Yerba Mate as Part of a Dietary Supplement Product? Check It for Interactions

We hold 68 real supplement products containing Yerba Mate, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yerba Mate. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Yerba Mate — 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 Yerba Mate 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 Yerba Mate
Steady interest

#1,067 of 1,452 supplements looked up here in the last 7 days

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

#471 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 Yerba Mate

What is Yerba Mate?

Yerba Mate
  • Energy and alertness
  • Weight loss
  • Mental focus
  • Digestive support
  • Antioxidant support

Yerba mate is a caffeine-containing herbal beverage from South America that is widely enjoyed for its stimulating, coffee-like effects. While it is rich in antioxidants and is being studied for weight, blood sugar, and cholesterol, strong human evidence for most health claims is limited. Drinking very hot mate over many years has been linked to higher risk of certain cancers, so enjoy it warm and in moderation.

Read the full Yerba Mate monograph & all interactions
Keep checking

Other Drugs & Yerba Mate

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

8Major
504Moderate
573Minor
1,744No known interaction
8 Major 504 Moderate 573 Minor 1,744 No interaction
Major

8 interactions

Moderate

504 interactions

Showing 60 of 504 moderate interactions — see all 504 on the Yerba Mate page.

Minor

573 interactions

Showing 60 of 573 minor interactions — see all 573 on the Yerba Mate page.

No interaction 1,744 drugs checked — show the list

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

Showing the 60 most looked-up of 1,744 medications checked with no known interaction — see the full Yerba Mate list.

See the full Yerba Mate 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
Yerba Mate 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 Yerba Mate and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions

Can you take Yerba Mate 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.
Why are there 2 interactions listed for Yerba Mate and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine belongs to more than one drug category, and Yerba Mate 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 Yerba Mate 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 Yerba Mate?

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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.