Drug & supplement interaction

Propolis + Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen brand name: Combogesic.

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

Acetaminophen, Ibuprofen falls into 4 drug categories that Propolis can interact with; the most serious is rated moderate. Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Propolis and Acetaminophen, Ibuprofen

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Propolis interacts with whole categories of medication. Acetaminophen, Ibuprofen falls into 4 of those categories, so it can interact with Propolis in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 4

Why this applies to Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Propolis interacts with.

Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP1A2.
In vitro research shows that propolis extract can inhibit CYP1A2. However, animal research shows that propolis extract does not significantly affect CYP1A2 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP1A2 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect. This effect has not been reported in humans.
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 short version for Combogesic, which combines acetaminophen and ibuprofen. The concern on file is that propolis might slow down a liver enzyme called CYP1A2, and in theory that could let drugs cleared by that pathway build up a bit. Neither of these pain relievers leans heavily on CYP1A2, and this idea comes only from lab dish studies. In animals, propolis didn't actually change this enzyme's activity, and nothing like this has been seen in people.

So in everyday terms, taking propolis with Combogesic is very unlikely to cause a problem. If you take high-dose propolis supplements often, it never hurts to mention it to your pharmacist, especially since both drugs already have their own dosing limits.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Naramoto K, Kato M, Ichihara K. Effects of an ethanol extract of Brazilian green propolis on human cytochrome P450 enzyme activities in vitro. J Agric Food Chem 2014;62(46):11296-302. PubMed
  2. Ryu CS, Oh SJ, Oh JM, et al. Inhibition of cytochrome P450 by propolis in human liver microsomes. Toxicol Res 2016;32(3):207-13. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 4

Acetaminophen, Ibuprofen also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2C9.
In vitro research shows that propolis extract can inhibit CYP2C9. However, animal research shows that propolis extract does not significantly affect CYP2C9 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2C9 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect. This effect has not been reported in humans.
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

Combogesic combines two pain relievers, and the ibuprofen part is partly cleared by a liver enzyme called CYP2C9. In a test tube, propolis can slow that enzyme down. In theory, slowing it could let ibuprofen build up a bit, which might mean more of its usual side effects like stomach upset, heartburn, or a higher risk of stomach irritation. The acetaminophen half is handled by different pathways, so this concern is really about the ibuprofen.

Here is the reassuring part: this is only laboratory data. In animal studies, propolis did not meaningfully change this enzyme, likely because little of it actually reaches the bloodstream. Nothing like this has been reported in people. Still, if you take concentrated propolis daily, mention it to your pharmacist so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Naramoto K, Kato M, Ichihara K. Effects of an ethanol extract of Brazilian green propolis on human cytochrome P450 enzyme activities in vitro. J Agric Food Chem 2014;62(46):11296-302. PubMed
  2. Ryu CS, Oh SJ, Oh JM, et al. Inhibition of cytochrome P450 by propolis in human liver microsomes. Toxicol Res 2016;32(3):207-13. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 4

Acetaminophen, Ibuprofen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, propolis might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that propolis water extract and the propolis constituent, caffeic acid phenethyl ester, can inhibit platelet aggregation. Additionally, evidence from an animal model shows that taking propolis in addition to warfarin decreases INR, suggesting that propolis can decrease the effectiveness of warfarin.
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 to know about Combogesic: the ibuprofen part is already a blood thinner of sorts. Like other NSAIDs, it can make platelets a little less sticky and can irritate the stomach lining. Propolis, in early lab studies, seems to do something similar by slowing platelets down. So the worry is that stacking the two could nudge your bleeding risk up a bit, meaning easier bruising, nosebleeds, or stomach upset and bleeding.

I want to be honest that this is theoretical, based only on test-tube and animal research, not real patient cases. For most folks taking Combogesic occasionally, propolis is unlikely to cause trouble. Still, if you use either one regularly or have a bleeding history, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chen, T. G., Lee, J. J., Lin, K. H., Shen, C. H., Chou, D. S., and Sheu, J. R. Antiplatelet activity of caffeic acid phenethyl ester is mediated through a cyclic GMP-dependent pathway in human platelets. Chin J Physiol 6-30-2007;50(3):121-126.
  2. Akbay E, Özenirler Ç, Çelemli ÖG, Durukan AB, Onur MA, Sorkun K. Effects of propolis on warfarin efficacy. Kardiochir Torakochirurgia Pol. 2017;14(1):43-46. PubMed
  3. Zhang YX, Yang TT, Xia L, Zhang WF, Wang JF, Wu YP. Inhibitory Effect of Propolis on Platelet Aggregation In Vitro. J Healthc Eng. 2017;2017:3050895. PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

4 of 4

Acetaminophen, Ibuprofen also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, propolis might increase levels of drugs metabolized by CYP2E1.
In vitro research shows that propolis can inhibit CYP2E1. This effect has not been reported in humans.
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

Combogesic combines acetaminophen and ibuprofen. The piece worth knowing here is that acetaminophen is partly handled by a liver enzyme called CYP2E1. In test-tube studies, propolis seems to slow that enzyme down. In theory, blocking CYP2E1 could shift how acetaminophen is broken down, which is interesting because CYP2E1 is the pathway that creates a small amount of a liver-stressing byproduct.

Here is the honest part: this has only been seen in lab dishes, never confirmed in real people, so I wouldn't lose sleep over it. There's no clear evidence propolis changes how this medicine works for you. Just keep your acetaminophen within the recommended daily limit, and if you take propolis regularly, mention it to your pharmacist or doctor so they have the full picture.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Ryu CS, Oh SJ, Oh JM, et al. Inhibition of cytochrome P450 by propolis in human liver microsomes. Toxicol Res 2016;32(3):207-13. 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

Propolis Also Interacts With Other Medications

Propolis has 920 moderate known drug interactions in our database — the Acetaminophen, Ibuprofen one above is among them. If you take anything else, check it against the full list below.

Moderate 920 No known interaction 1,910 (incl. Acetaminophen, Ibuprofen)
Taking anything else?

Check Another of Your Medications Against Propolis

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Ibuprofen

This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Ibuprofen page lists 342 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Piracetam (major).

By severity: 7 major · 290 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Ibuprofen page

“Combogesic pairs acetaminophen with ibuprofen, so it inherits the vulnerabilities of both drugs, and its supplement list deserves real attention before you add anything to it. Of the 342 ingredients on file, 7 carry a major rating, and those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Ibuprofen interaction page

One more smart check

Taking Propolis as Part of a Dietary Supplement Product? Check It for Interactions

We hold 723 real supplement products containing Propolis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Propolis. Your product may carry other ingredients that interact with Acetaminophen, Ibuprofen too, on top of Propolis — 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 Propolis and Acetaminophen, Ibuprofen 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 Propolis
Top 25%

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

29 days ago today
Medication Acetaminophen, Ibuprofen
Top 25%

#402 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 Propolis

What is Propolis?

Propolis
  • Cold sores and herpes lesions (topical)
  • Sore throat and mouth sores
  • Wound and skin healing
  • Immune support
  • Oral and gum health

Propolis is a natural, resin-like substance made by bees that has antimicrobial and anti-inflammatory properties in lab studies. Early research suggests it may help with cold sores, mouth sores, and minor wounds, but high-quality evidence is limited for most uses. It is generally well tolerated, but allergic reactions can occur, especially in people allergic to bee products.

Read the full Propolis monograph & all interactions
Keep checking

Other Drugs & Propolis

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

0Major
920Moderate
0Minor
1,909No known interaction
920 Moderate 1,909 No interaction
Moderate

920 interactions

Showing 60 of 920 moderate interactions — see all 920 on the Propolis page.

No interaction 1,909 drugs checked — show the list

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

Showing the 60 most looked-up of 1,909 medications checked with no known interaction — see the full Propolis list.

See the full Propolis interactions page
See every supplement checked against Acetaminophen, Ibuprofen, 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
Propolis monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Ibuprofen supplement interactions › Every supplement checked against Acetaminophen, Ibuprofen, 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 Propolis and Acetaminophen, Ibuprofen Together: Common Questions

Can you take Propolis with Acetaminophen, Ibuprofen?
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 4 interactions listed for Propolis and Acetaminophen, Ibuprofen?
Acetaminophen, Ibuprofen belongs to more than one drug category, and Propolis 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 Propolis and Acetaminophen, Ibuprofen 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, Ibuprofen and Propolis?

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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.