Drug & supplement interaction

Propolis + Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride brand name: Hycofenix.

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

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Propolis and Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Propolis interacts with whole categories of medication. Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride falls into 2 of those categories, so it can interact with Propolis in 2 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 2

Why this applies to Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 piece of your Hycofenix that matters most for this question: the hydrocodone part. Hydrocodone is partly turned into its stronger pain-relieving form (hydromorphone) by a liver enzyme called CYP2D6. In test-tube studies, propolis can slow that enzyme down. If that happened in your body, it could nudge hydrocodone toward more sedation, dizziness, constipation, or slowed breathing, while possibly giving slightly less cough relief.

The reassuring news: this is only seen in lab dishes. Animal studies didn't show a real effect, likely because propolis isn't well absorbed, and it has never been reported in people. Normal amounts are unlikely to cause trouble, but very concentrated supplement doses are less studied. Just run it by your pharmacist or doctor first.

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 2

Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 for your Hycofenix, which combines guaifenesin, hydrocodone, and pseudoephedrine. The piece that matters here is the hydrocodone, an opioid cough suppressant that your liver processes partly through an enzyme called CYP3A4. In a test tube, some propolis compounds appear to slow that enzyme down. If that happened in your body, hydrocodone could build up a bit, which in theory means more drowsiness, dizziness, constipation, or slowed breathing.

The reassuring part is that this is very weak, lab-only evidence. Animal studies didn't show a real effect, and it has never been reported in people, likely because propolis is poorly absorbed. Occasional or normal supplement amounts are unlikely to cause trouble. Still, since opioids deserve respect, mention propolis to your pharmacist or doctor just to be safe.

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

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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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. Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride)
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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride

This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride page lists 241 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), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 190 moderate · 38 minor.

From our pharmacist’s overview on the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride page

“Hycofenix combines guaifenesin with hydrocodone, an opioid, and pseudoephedrine, a decongestant, so supplements can collide with it from two directions at once. That is why this list of 241 ingredients deserves real caution, starting with the 13 rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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%

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

29 days ago today
Medication Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride
Top 25%

#703 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride, 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride supplement interactions › Every supplement checked against Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride, 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride Together: Common Questions

Can you take Propolis with Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride?
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 2 interactions listed for Propolis and Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride?
Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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 Guaifenesin, Hydrocodone Bitartrate, Pseudoephedrine Hydrochloride 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.