Drug & supplement interaction

Propolis + Acetaminophen, Caffeine, Codeine, Salicylamide

Acetaminophen, Caffeine, Codeine, Salicylamide brand names: Codalan No.1, Codalan No.2, Codalan No.3.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Caffeine, Codeine, Salicylamide 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, Caffeine, Codeine, Salicylamide

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, Caffeine, Codeine, Salicylamide 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, Caffeine, Codeine, Salicylamide

Acetaminophen, Caffeine, Codeine, Salicylamide 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 product: the codeine part is a prodrug. Your body uses an enzyme called CYP2D6 to convert codeine into morphine, which is what actually relieves pain. In lab dishes, propolis can block that enzyme. If that blocking happened in real life, you would get less pain relief from the codeine, not more, because less of it would be turned into the active form.

The good news is this is mostly theoretical. It comes from test-tube studies, and animal research didn't show a meaningful effect, likely because not much propolis reaches the bloodstream. It hasn't been reported in people. Concentrated propolis supplements are more of a question mark than small culinary amounts. If you take both regularly, just mention it to your pharmacist or doctor.

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, Caffeine, Codeine, Salicylamide 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

This combination pill mostly matters because of its caffeine portion, which the liver clears using an enzyme called CYP1A2. In a test tube, propolis can slow that enzyme down, which in theory could let caffeine linger longer and leave you feeling jittery, wired, or having trouble sleeping, with a faster heartbeat. The acetaminophen, codeine, and salicylamide pieces aren't the main concern here.

Here's the reassuring part: this effect has only shown up in lab dishes. In animal studies, propolis didn't meaningfully change this enzyme, likely because very little of it survives digestion. It has never been reported in people. Normal use is unlikely to cause trouble, but if you take concentrated propolis daily, mention it to your pharmacist or doctor.

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, Caffeine, Codeine, Salicylamide 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

This combination pill includes codeine, and here's the wrinkle: codeine is a prodrug, meaning your body has to convert it into morphine before it does much for pain. The CYP3A4 enzyme is one pathway involved in handling codeine, so in theory propolis nudging that enzyme could shift how the medicine is processed. The same goes for the acetaminophen and caffeine in the mix.

Here's the reassuring part: this concern comes only from lab and animal studies, and it has never been reported in actual people. Researchers think propolis is too poorly absorbed to matter much in the body. Food or normal supplement amounts are very unlikely to cause trouble. Still, if you take high-dose propolis regularly, just give your pharmacist a quick heads-up.

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, Caffeine, Codeine, Salicylamide 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 piece that matters in this combo product: the acetaminophen. Your liver uses an enzyme called CYP2E1 to handle a small slice of acetaminophen, and in test-tube studies only, propolis appears to slow that enzyme down. The theory is that propolis could nudge acetaminophen levels a little higher. The codeine and caffeine pieces are cleared mostly by other pathways, so they aren't really the concern here.

Honestly, this has never been shown to happen in actual people, so I wouldn't lose sleep over it. The bigger everyday rule with any acetaminophen product is simply not overdoing the total daily dose. If you take propolis regularly and use this often, it's worth a quick chat with your pharmacist, but don't change anything on your own.

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, Codeine, Salicylamide one above is among them. If you take anything else, check it against the full list below.

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, Codeine, Salicylamide

This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine, Salicylamide page lists 303 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: 15 major · 244 moderate · 44 minor.

Open the Acetaminophen, Caffeine, Codeine, Salicylamide 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, Codeine, Salicylamide 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, Codeine, Salicylamide 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, Codeine, Salicylamide
Top half

#1,352 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
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
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

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Pharmacist Counseling Corner

Taking Propolis and Acetaminophen, Caffeine, Codeine, Salicylamide Together: Common Questions

Can you take Propolis with Acetaminophen, Caffeine, Codeine, Salicylamide?
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, Caffeine, Codeine, Salicylamide?
Acetaminophen, Caffeine, Codeine, Salicylamide 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, Codeine, Salicylamide 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.