Kratom + Acetaminophen, Butalbital, Caffeine
Acetaminophen, Butalbital, Caffeine brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, and others.
Acetaminophen, Butalbital, Caffeine falls into 2 drug categories that Kratom can interact with; the most serious is rated moderate. Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.
Read the full interaction reportKratom and Acetaminophen, Butalbital, Caffeine
These two interact in 2 distinct ways. Each one is explained separately below.
Why Are There 2 Interactions?
Kratom interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine falls into 2 of those categories, so it can interact with Kratom in 2 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 2Why this applies to Acetaminophen, Butalbital, Caffeine
Acetaminophen, Butalbital, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Kratom interacts with.
In vitro research suggests that kratom extract inhibits the activity of CYP1A2. In one case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited CYP1A2-mediaed metabolism of ziprasidone which consequently increased systemic exposure to serotonin.
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 piece of this combo product that matters: the caffeine part is cleared by a liver enzyme called CYP1A2. Lab studies (not human trials) suggest kratom may slow that enzyme down. If that happened in your body, caffeine could hang around longer, so you might feel jittery, anxious, have a racing heart, or trouble sleeping. The acetaminophen and butalbital pieces aren't really driven by this same pathway.
Keep in mind this is theoretical, based only on test-tube data, so it may not amount to much in real life. Still, kratom on its own carries serious risks, and butalbital is a sedative. Please check with your pharmacist or doctor before mixing the two.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 2Acetaminophen, Butalbital, Caffeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity. A pharmacokinetic study in adults shows that taking kratom tea 2 grams modestly increases the plasma concentration time-curve (AUC) and maximum concentration (Cmax) of CYP3A4 probe midazolam by 40-50% and its CYP3A4-mediated metabolites 18-27%. However, a lack of change in the half-life of midazolam and a simulation of the kratom-midazolam interaction suggest that kratom inhibits CYP3A4 enzymes in the small intestine but not the liver. Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom. In another case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It is hypothesized that CYP3A4 inhibition by kratom reduced metabolism of desvenlafaxine, trazodone, and ziprasidone and consequently increased systemic exposure to serotonin.
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 for your headache medicine (the acetaminophen, butalbital, and caffeine combo). One of these ingredients, butalbital, is partly broken down by a liver and gut enzyme called CYP3A4. Lab studies suggest kratom can slow that enzyme down a bit. In theory, that could let butalbital build up slightly, nudging up its sedative effects.
What might that feel like? More drowsiness, dizziness, slowed breathing, or feeling foggy, especially since both kratom and butalbital already calm the nervous system. That overlap is the bigger concern here, more so than the enzyme detail. This is theoretical and graded as weak evidence, so I'm not trying to alarm you. Still, please check with your pharmacist or doctor before combining them.
- Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
- Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113. PubMed
- Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
- Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. 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.
Kratom Also Interacts With Other Medications
Kratom has 982 moderate, 12 minor 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 Kratom
We haven’t checked that one against Kratom yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Kratom. Pick one to open its full report.
Questions About Kratom or Acetaminophen, Butalbital, Caffeine
These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Kratom or Acetaminophen, Butalbital, Caffeine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:
Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.
See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine
This page covers Kratom 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 Kratom as Part of a Dietary Supplement Product? Check It for Interactions
We hold 8 real supplement products containing Kratom, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kratom. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Kratom — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Kratom 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.
#316 of 1,452 supplements looked up here in the last 7 days
#1,513 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 Kratom
What is Kratom?
- Pain relief
- Opioid withdrawal symptoms
- Anxiety and stress
- Low energy or fatigue
- Mood enhancement
Kratom is a Southeast Asian plant whose leaves act on the brain's opioid receptors and can produce both stimulant-like and opioid-like effects. It is not approved or proven safe by health regulators, carries real risks of dependence and serious harm, and its legal status varies widely. Talk to a pharmacist or doctor before considering it.
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 & Kratom
Browse every other medication we’ve checked against Kratom — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
982 interactions
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Metronidazole ›
- Diphenhydramine ›
- Hydrocortisone ›
- Methylphenidate ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Phenylephrine ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meprobamate ›
- Nortriptyline ›
- Oxymorphone ›
- Propoxyphene ›
- Rifampin ›
- Selegiline ›
Showing 60 of 982 moderate interactions — see all 982 on the Kratom page.
12 interactions
No interaction 1,835 drugs checked — show the list
We also checked Kratom against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Aspirin ›
- Ivermectin ›
- Rosuvastatin ›
- Docusate ›
- Hydroxyurea ›
- Valacyclovir ›
- Ibuprofen ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Acyclovir ›
- Doxycycline ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Valsartan ›
- Levothyroxine Sodium ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Minoxidil ›
- Ezetimibe ›
- Levodopa ›
- Mitomycin ›
- Cefaclor ›
- Vancomycin ›
- Lenvatinib ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Procainamide ›
- Amoxicillin, Clavulanate Potassium ›
- Hydroxychloroquine ›
- Bentoquatam ›
- Triptorelin ›
- Tenecteplase ›
- Azelaic Acid ›
- Digoxin ›
- Dextrothyroxine ›
- Lomustine ›
- Pizotifen ›
- Tocainide ›
- Acetylsalicylic Acid ›
- Diclofenac Sodium ›
- Hydrochlorothiazide ›
- Rocuronium ›
- Telmisartan ›
- Succimer ›
Showing the 60 most looked-up of 1,835 medications checked with no known interaction — see the full Kratom 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 Kratom — 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 Kratom and Acetaminophen, Butalbital, Caffeine Together: Common Questions
Can you take Kratom with Acetaminophen, Butalbital, Caffeine?
Why are there 2 interactions listed for Kratom and Acetaminophen, Butalbital, Caffeine?
How serious is the Kratom and Acetaminophen, Butalbital, Caffeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Butalbital, Caffeine and Kratom?
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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.