Drug & supplement interaction

Propolis + Acetaminophen, Caffeine, Isometheptene

Acetaminophen, Caffeine, Isometheptene brand name: Migralam.

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

Acetaminophen, Caffeine, Isometheptene falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Propolis and Acetaminophen, Caffeine, Isometheptene

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

Why Are There 3 Interactions?

Propolis interacts with whole categories of medication. Acetaminophen, Caffeine, Isometheptene falls into 3 of those categories, so it can interact with Propolis in 3 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 3

Why this applies to Acetaminophen, Caffeine, Isometheptene

Acetaminophen, Caffeine, Isometheptene 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 Migralam (acetaminophen, caffeine, and isometheptene). The piece that matters here is the caffeine, which your liver clears using an enzyme called CYP1A2. In test-tube studies, propolis appeared to slow that enzyme down, which could in theory let caffeine linger longer and build up. If that happened, you might feel more of caffeine's usual effects, like jitteriness, a racing heart, trouble sleeping, or an upset stomach.

But I want to keep this in perspective. This concern comes only from lab work, and animal studies didn't show a real effect, likely because not much propolis actually reaches the bloodstream. It hasn't been reported in people. Occasional, normal use is unlikely to cause trouble, but if you take concentrated propolis daily, mention it to your pharmacist or doctor.

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 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Caffeine, Isometheptene also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP3A4.
Some in vitro research shows that propolis extract can inhibit CYP3A4; however, other in vitro research shows that propolis has no effect on CYP3A4 activity. Furthermore, animal research shows that propolis extract does not significantly affect CYP3A4 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that might in inhibit CYP3A4 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 gist with Migralam (the acetaminophen, caffeine, and isometheptene combo used for migraines) and propolis. The theory is that propolis might slow down a liver enzyme called CYP3A4, which helps process certain medicines. If that enzyme were blocked, levels of a drug could creep up, which in theory might mean a little more of the usual effects, like jitteriness or a faster heartbeat from the caffeine and isometheptene.

But honestly, I wouldn't lose sleep over this one. The evidence is very weak and comes only from lab and animal studies, with no reports of problems in real people. Concentrated propolis supplements are more of a question mark than small amounts, so if you take both regularly, just mention it to your pharmacist.

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 2E1 (CYP2E1) SUBSTRATES

3 of 3

Acetaminophen, Caffeine, Isometheptene 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

Here's the gist for Migralam, which combines acetaminophen, caffeine, and isometheptene. One enzyme that helps your liver break down acetaminophen is called CYP2E1. In test-tube studies, propolis seems to slow that enzyme down. If the same thing happened in people, acetaminophen could clear a little more slowly and hang around longer than usual.

The reassuring part: this has only been seen in lab dishes, never actually reported in humans, so the real-world risk looks low. Still, since acetaminophen is hard on the liver in large amounts, I'd avoid stacking extra acetaminophen products and keep your total daily dose sensible. Curious about your own situation? Run it by your pharmacist or doctor before combining them regularly.

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, Caffeine, Isometheptene 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, Caffeine, Isometheptene)
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, Caffeine, Isometheptene

This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Isometheptene page lists 248 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), Ephedra (major) and Grapefruit (major).

By severity: 11 major · 194 moderate · 43 minor.

Open the Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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%

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

29 days ago today
Medication Acetaminophen, Caffeine, Isometheptene
Top half

#1,301 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, Caffeine, Isometheptene, 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, Caffeine, Isometheptene supplement interactions › Every supplement checked against Acetaminophen, Caffeine, Isometheptene, 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, Caffeine, Isometheptene Together: Common Questions

Can you take Propolis with Acetaminophen, Caffeine, Isometheptene?
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 Propolis and Acetaminophen, Caffeine, Isometheptene?
Acetaminophen, Caffeine, Isometheptene 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, Caffeine, Isometheptene 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, Isometheptene 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.