Propolis + Acetaminophen, Butalbital, Caffeine
Acetaminophen, Butalbital, Caffeine brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, and others.
Acetaminophen, Butalbital, Caffeine 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 reportPropolis and Acetaminophen, Butalbital, Caffeine
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, Butalbital, Caffeine 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).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 3Why this applies to Acetaminophen, Butalbital, Caffeine
Acetaminophen, Butalbital, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Propolis interacts with.
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.
In your headache combo, the part that interacts here is the caffeine, which your liver clears using an enzyme called CYP1A2. In test-tube studies, propolis can slow that enzyme down. If that happened in your body, caffeine could hang around a bit longer and you might notice more jitteriness, a racing heart, trouble sleeping, or feeling wired.
Here's the reassuring part: this is only a theoretical concern from lab work. Animal studies didn't show a real effect, likely because not much propolis actually reaches the bloodstream. It has never been reported in people. Small amounts are unlikely to matter, but if you take concentrated propolis supplements daily, mention it to your pharmacist or doctor so they can keep an eye on things.
- 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
2 of 3Acetaminophen, Butalbital, Caffeine 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 gist if you take propolis along with your Tecnal or Esgic (the acetaminophen, butalbital, caffeine combo for tension headaches). In test-tube studies, propolis sometimes slows down a liver enzyme called CYP3A4, which helps break down the butalbital part of this medicine. In theory, if that enzyme were blocked, butalbital could build up and leave you feeling extra drowsy, foggy, or lightheaded.
That said, I want to keep this in perspective. This is only lab and animal data, and in animals propolis did not meaningfully change this enzyme, likely because so little gets into the bloodstream. It hasn't been reported as a real problem in people. Still, since butalbital is sedating, it's worth a quick chat with your pharmacist before combining them.
- 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
3 of 3Acetaminophen, Butalbital, Caffeine 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 gist with this headache combo and propolis. One concern centers on the acetaminophen (Tylenol) piece. Your liver uses an enzyme called CYP2E1 to handle a small portion of acetaminophen. In test-tube studies, propolis seems to slow that enzyme down a bit. If that slowing happened in people, it could shift how acetaminophen is processed. The interesting part is this pathway is the one that makes acetaminophen's harsh liver byproduct, so blocking it isn't clearly harmful and might even be neutral.
The honest truth is this is only laboratory data and has never been shown in humans. For most folks taking normal doses, propolis is unlikely to cause a real problem. Still, if you use acetaminophen products regularly, mention the propolis to your pharmacist so they can keep an eye on your total daily acetaminophen.
- 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, Butalbital, Caffeine 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, Butalbital, Caffeine
This page covers Propolis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine page lists 252 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 · 197 moderate · 44 minor.
From our pharmacist’s overview on the Acetaminophen, Butalbital, Caffeine page
“Alcohol is the interaction I would flag first for anyone taking acetaminophen, butalbital, and caffeine (Esgic, Fiogesic, and others). Drinking raises the risk of liver injury from the acetaminophen component, and 38 of the 252 supplement ingredients on file carry that same liver concern.”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Butalbital, Caffeine interaction page
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, Butalbital, Caffeine 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, Butalbital, Caffeine 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.
#248 of 1,452 supplements looked up here in the last 7 days
#1,544 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.
About Acetaminophen, Butalbital, and Caffeine
What Is Acetaminophen, Butalbital, and Caffeine Used For?
Brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, Esgic, Fioricet
This three-ingredient combination — butalbital, acetaminophen, and caffeine — is used to relieve the symptoms of tension headache (also called muscle contraction headache). All supported products, including tablets, capsules, and oral solution, share this same approved use.
It is worth knowing that evidence for using this combination to treat repeated, frequent tension headaches over time is limited. Because butalbital can be habit-forming, extended or repeated use is not recommended.
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 ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Acyclovir ›
- Doxycycline ›
- Methotrexate ›
- Lamotrigine ›
- Gabapentin ›
- Pregabalin ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Roxithromycin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Levothyroxine Sodium ›
- Dexmethylphenidate ›
- Levetiracetam ›
- Spironolactone ›
- Factor 7a ›
- Phentermine, Topiramate ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Phenylephrine ›
- Vancomycin ›
- Lenvatinib ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Pentobarbitone ›
- Bentoquatam ›
- Procainamide ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Azelaic Acid ›
- Digoxin ›
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, Butalbital, Caffeine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Butalbital, Caffeine 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, Butalbital, Caffeine 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, Butalbital, Caffeine Together: Common Questions
Can you take Propolis with Acetaminophen, Butalbital, Caffeine?
Why are there 3 interactions listed for Propolis and Acetaminophen, Butalbital, Caffeine?
How serious is the Propolis and Acetaminophen, Butalbital, Caffeine interaction?
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.