Drug & supplement interaction

Propolis + Acetaminophen, Hydrocodone

Acetaminophen, Hydrocodone brand names: Vicodin, Vicodin ES, Vicodin HP, Lortab, Norco 10/325, and others.

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

Acetaminophen, Hydrocodone 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 CYP2D6.

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

Propolis and Acetaminophen, Hydrocodone

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, Hydrocodone 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 2D6 (CYP2D6) SUBSTRATES

1 of 4

Why this applies to Acetaminophen, Hydrocodone

Acetaminophen, Hydrocodone falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Propolis interacts with.

Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2D6.
In vitro research shows that propolis extract can inhibit CYP2D6. However, animal research shows that propolis extract does not significantly affect CYP2D6 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2D6 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 wrinkle with this combo: the hydrocodone part of your Vicodin or Norco actually relies on an enzyme called CYP2D6 to turn it into hydromorphone, the form that does most of the pain relieving. In other words, hydrocodone is a bit of a prodrug. If propolis blocked that enzyme, the theory would be less pain relief, not more, since your body couldn't activate the medicine as well.

The good news is that this concern comes only from lab dish studies. In animals, propolis didn't meaningfully change CYP2D6, and it has never been reported in people. So I wouldn't lose sleep over it. Still, if you take concentrated propolis supplements daily, mention it to your pharmacist so they can keep an eye on how well your pain is controlled.

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 1A2 (CYP1A2) SUBSTRATES

2 of 4

Acetaminophen, Hydrocodone also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

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 honest picture on combining propolis with your Vicodin or Norco (acetaminophen plus hydrocodone). The concern on file is that propolis might slow down a liver enzyme called CYP1A2. In theory, if that enzyme is blocked, a drug it handles could build up a bit and cause stronger effects like extra drowsiness, dizziness, constipation, or slowed breathing from the hydrocodone side.

But I want to keep this in perspective. This is based only on lab-dish studies, and when researchers actually gave propolis to animals, it didn't meaningfully change this enzyme. It has never been reported as a problem in people, and CYP1A2 isn't even the main pathway for this medication. So for most folks this is very unlikely to matter. Still, since this combo can make you sleepy on its own, it's worth a quick word with your pharmacist if you take propolis regularly.

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

3 of 4

Acetaminophen, Hydrocodone 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 your Norco (acetaminophen and hydrocodone). The hydrocodone part is actually a prodrug of sorts, your liver's CYP3A4 enzyme is one of the pathways that processes it. In a test tube, some propolis extracts seem to slow CYP3A4 down a little. If that happened in your body, hydrocodone could linger longer and you might feel more drowsy, dizzy, constipated, or short of breath.

But honestly, I wouldn't lose sleep over this one. This concern comes only from lab and animal studies, and even rat studies didn't show a real effect. It's never been reported in people, likely because propolis just doesn't get absorbed well. Still, if you take concentrated propolis often, mention it to your pharmacist so we 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

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

4 of 4

Acetaminophen, Hydrocodone 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 practical picture with your Norco or Vicodin (acetaminophen plus hydrocodone). The acetaminophen part is partly handled by a liver enzyme called CYP2E1. In test-tube studies, propolis seems to slow that enzyme down. Interestingly, CYP2E1 is the same pathway that turns acetaminophen into a byproduct that can stress the liver, so in theory slowing it could actually mean less of that harmful byproduct, not more.

The honest takeaway: this is lab-only science. It has never been shown to matter in real people, and small amounts of propolis are very unlikely to cause a problem. Still, since acetaminophen and the liver are involved, it's worth a quick chat with your pharmacist or doctor before pairing them, especially if you take acetaminophen 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, Hydrocodone 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, Hydrocodone)
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, Hydrocodone

This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Hydrocodone page lists 270 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 Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 215 moderate · 44 minor.

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

“Someone taking hydrocodone with acetaminophen (Vicodin, Norco) for post-surgical or dental pain often reaches for a sleep aid, kava, or a glass of wine at night, and that is exactly where the risk sits. This combination calls for genuine vigilance.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Hydrocodone 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, Hydrocodone 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, Hydrocodone 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%

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

29 days ago today
Medication Acetaminophen, Hydrocodone
Top half

#1,199 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, Hydrocodone, 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, Hydrocodone supplement interactions › Every supplement checked against Acetaminophen, Hydrocodone, 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, Hydrocodone Together: Common Questions

Can you take Propolis with Acetaminophen, Hydrocodone?
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, Hydrocodone?
Acetaminophen, Hydrocodone 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, Hydrocodone 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, Hydrocodone 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.