Propolis + Acetaminophen, Caffeine, Codeine
Acetaminophen, Caffeine, Codeine brand names: Gesic C8, Gesic C15, Lenoltec 2, Gesic C30, Lenoltec 3, and others.
Acetaminophen, Caffeine, Codeine 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 reportPropolis and Acetaminophen, Caffeine, Codeine
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 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).
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
1 of 4Why this applies to Acetaminophen, Caffeine, Codeine
Acetaminophen, Caffeine, Codeine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Propolis interacts with.
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.
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.
Here's something worth knowing about this combo. The codeine in your tablet is actually a prodrug, meaning it does nothing for pain until your liver's CYP2D6 enzyme converts it into morphine, which is the part that actually relieves pain. Lab (test-tube) studies hint that propolis might slow down that very enzyme. If it did, you'd theoretically get less morphine formed, so your pain relief from the codeine could be weaker, not stronger.
The good news: this is only seen in lab dishes. Animal studies didn't show a real effect, and nothing has been reported in actual people, likely because propolis is poorly absorbed. So I wouldn't lose sleep over normal use. Still, if you take concentrated propolis daily and notice your pain medicine isn't working as well, mention it to your pharmacist or doctor.
- 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
- 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
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
2 of 4Acetaminophen, Caffeine, Codeine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.
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.
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.
Here's the thing about this combo product: it's the caffeine piece that connects to propolis. In lab dishes, propolis can slow down CYP1A2, the liver enzyme that clears caffeine. If that slowdown actually happened in your body, caffeine could linger a bit longer and you might feel jittery, have a racing heart, or trouble sleeping. The codeine and acetaminophen parts aren't really involved here.
But I want to keep this in perspective. This is only a theoretical, test-tube finding, and animal studies didn't show a real effect, likely because not much propolis survives digestion. It's never been reported in people. Everyday cold-sore amounts shouldn't matter. If you take concentrated propolis daily, just mention it to your pharmacist.
- 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
- 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
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 4Acetaminophen, Caffeine, Codeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
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.
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.
Here's the situation with your acetaminophen, caffeine, and codeine combo. The codeine piece is interesting because codeine is a prodrug, meaning your body has to convert it into morphine (mostly through a different enzyme called CYP2D6) before it does much. The interaction on file involves CYP3A4, which handles part of how your body processes these ingredients. In theory, concentrated propolis might slow CYP3A4 a little, which could nudge drug levels up and possibly add to drowsiness, constipation, or that foggy feeling codeine can cause.
That said, this is very weak evidence. It comes only from lab and animal studies and hasn't actually been seen in people, partly because propolis is poorly absorbed. Everyday amounts likely won't matter much. Still, since codeine is a strong medicine, run it by your pharmacist or doctor before pairing it with concentrated propolis.
- 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
- 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
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
4 of 4Acetaminophen, Caffeine, Codeine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
In vitro research shows that propolis can inhibit CYP2E1. This effect has not been reported in humans.
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.
Here's the honest picture with this combo pill. The interaction on file involves an enzyme called CYP2E1, and lab studies (in test tubes, not people) suggest propolis might slow it down a bit. For this medication, the part that matters most is the acetaminophen piece, since CYP2E1 is one of the pathways that handles it. In theory, blocking that enzyme could shift how acetaminophen is processed.
That said, this is very early, theoretical data and has never actually been shown in humans, so I wouldn't lose sleep over it. The codeine and caffeine pieces aren't really the concern here. The bigger everyday rule with any acetaminophen product is simply not to overdo the dose. If you use propolis regularly, just mention it to your pharmacist so they can keep an eye on things.
- 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.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Propolis Also Interacts With Other Medications
Propolis has 920 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Codeine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Propolis
We haven’t checked that one against Propolis yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Propolis. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Caffeine, Codeine
This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine 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.
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 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:
Where Propolis and Acetaminophen, Caffeine, Codeine 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.
#226 of 1,452 supplements looked up here in the last 7 days
#127 of 2,830 medications looked up here in the last 7 days
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.
About Propolis
What is 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.
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.
No drugs match “”.
920 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Ketoprofen ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meloxicam ›
- Nortriptyline ›
- Propoxyphene ›
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.
- Levothyroxine ›
- Methylphenidate ›
- Ivermectin ›
- Rosuvastatin ›
- Escitalopram ›
- Isotretinoin ›
- Tirzepatide ›
- Docusate ›
- Hydroxyurea ›
- Metformin ›
- Valacyclovir ›
- Sumatriptan ›
- Semaglutide ›
- Levothyroxine, Liothyronine ›
- Methotrexate ›
- Amoxicillin ›
- Lisinopril ›
- Bupropion ›
- Azithromycin ›
- Pregabalin ›
- Doxycycline ›
- Gabapentin ›
- Lamotrigine ›
- Acyclovir ›
- Methylene Blue ›
- Ciprofloxacin ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Ezetimibe ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Cyclopentolate ›
- Cephalexin ›
- Atenolol, Chlorthalidone ›
- Avatrombopag Maleate ›
- Thyroid Hormone ›
- Levetiracetam ›
- Carbidopa, Levodopa ›
- Mannitol ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Levodopa ›
- Roxithromycin ›
- Canagliflozin, Metformin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Enalapril Maleate ›
- Spironolactone ›
- Acarbose ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Alginic Acid, Aluminum Hydroxide ›
- Mitomycin ›
- Ephedrine, Phenobarbital, Theophylline ›
- Atenolol ›
- Amobarbital, Ephedrine Sulfate ›
- Flutemetamol F-18 ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Charcoal (otc Drug) ›
- Efgartigimod Alfa-fcab ›
- Levothyroxine Sodium ›
- Aminophylline, Amobarbital, Ephedrine ›
Showing the 60 most looked-up of 1,909 medications checked with no known interaction — see the full Propolis list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Acetaminophen, Caffeine, Codeine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Codeine as a medicine that can lower these. This is not an interaction with Propolis — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Acetaminophen, Caffeine, Codeine nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Propolis and Acetaminophen, Caffeine, Codeine Together: Common Questions
Can you take Propolis with Acetaminophen, Caffeine, Codeine?
Why are there 4 interactions listed for Propolis and Acetaminophen, Caffeine, Codeine?
How serious is the Propolis and Acetaminophen, Caffeine, Codeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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