Drug & supplement interaction

Yerba Mate + Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium

Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium brand name: Hista-Derfule.

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

Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium falls into 3 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
Interactions3
EvidenceC
What do Severity, Likelihood & Evidence mean?
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Interaction report

Yerba Mate and Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Yerba Mate interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium falls into 3 of those categories, so it can interact with Yerba Mate in 3 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 3

Why this applies to Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium

Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium 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

This combination product contains phenylpropanolamine, which is a decongestant and a stimulant in its own right. Yerba mate brings caffeine to the table, and stacking two stimulants together can simply add up. You may notice a jittery, wired feeling, a racing or pounding heart, higher blood pressure, trouble sleeping, or feeling on edge.

Keep in mind this is largely a theoretical concern based on expert opinion, not strong studies, so it is not something to panic over. Interestingly, the opium and chlorpheniramine pieces are sedating, so the caffeine could blunt some of that drowsiness too. If you tend to drink a lot of mate or feel your heart pounding, it is worth a quick chat with your pharmacist 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
Moderate

PHENYLPROPANOLAMINE

2 of 3

Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium also falls under PHENYLPROPANOLAMINE.

Theoretically, phenylpropanolamine might increase the risk of hypertension as well as the levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.
Severity Moderate Likelihood Probable Evidence B

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 part that matters for your Hista-Derfule combo: it contains phenylpropanolamine, a decongestant-type stimulant. Yerba mate brings its own dose of caffeine to the table. When you put the two together, they can push your blood pressure up more than either would alone. On top of that, phenylpropanolamine seems to slow how fast your body clears caffeine, so the caffeine can hang around longer and hit harder.

In real life that might mean a racing or pounding heart, jitteriness, trouble sleeping, headache, or feeling wired. This is rated moderate and is partly theoretical, so don't panic, but if you already have high blood pressure or notice these symptoms, ease back on the mate and check in with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71. PubMed
  2. Lake CR, Rosenberg DB, Gallant S, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990;47:675-85. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium 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

This combo product mixes a pain reliever (acetaminophen), an antihistamine (chlorpheniramine), a decongestant (phenylpropanolamine), and opium, which is a mild opioid. The note on file is mostly theoretical: in lab dishes, yerba mate slowed down a liver enzyme called CYP3A4 that helps clear some of these ingredients. If that happened in your body, levels could creep up a little, possibly adding to drowsiness, dizziness, dry mouth, or constipation from the opioid and antihistamine.

Keep in mind this is based only on test-tube research, so real-world effects are uncertain and likely small. Still, yerba mate has its own caffeine, which can clash with the sleepy and the stimulating parts of this medicine. Please run it by your pharmacist or doctor before mixing them.

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, 574 minor known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 504 Minor 574 No known interaction 1,744 (incl. Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium)
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, Chlorpheniramine, Phenylpropanolamine, Opium

This page covers Yerba Mate only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium page lists 332 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: 18 major · 267 moderate · 47 minor.

From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium page

“Hista-Derfule is really four medicines at once: acetaminophen, the antihistamine chlorpheniramine, the decongestant phenylpropanolamine, and opium. That mix is why I read its 332 supplement interactions with genuine care, starting with the 18 rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium 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, Chlorpheniramine, Phenylpropanolamine, Opium 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, Chlorpheniramine, Phenylpropanolamine, Opium 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
Top half

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

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium
Top 5%

#50 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
574Minor
1,743No known interaction
8 Major 504 Moderate 574 Minor 1,743 No interaction
Major

8 interactions

Moderate

504 interactions

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

Minor

574 interactions

Showing 60 of 574 minor interactions — see all 574 on the Yerba Mate page.

No interaction 1,743 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 1,743 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, Chlorpheniramine, Phenylpropanolamine, Opium, 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, Chlorpheniramine, Phenylpropanolamine, Opium supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium, 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, Chlorpheniramine, Phenylpropanolamine, Opium Together: Common Questions

Can you take Yerba Mate with Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium?
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 3 interactions listed for Yerba Mate and Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium?
Acetaminophen, Chlorpheniramine, Phenylpropanolamine, Opium 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, Chlorpheniramine, Phenylpropanolamine, Opium 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

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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.