Higenamine + Aspirin, Butalbital, Caffeine
Aspirin, Butalbital, Caffeine brand name: Fiorinal.
Aspirin, Butalbital, Caffeine falls into 3 drug categories that Higenamine can interact with; the most serious is rated moderate. Theoretically, higenamine might increase the levels and clinical effects drugs metabolized by CYP3A4.
Read the full interaction reportHigenamine and Aspirin, Butalbital, Caffeine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Higenamine interacts with whole categories of medication. Aspirin, Butalbital, Caffeine falls into 3 of those categories, so it can interact with Higenamine in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
1 of 3Why this applies to Aspirin, Butalbital, Caffeine
Aspirin, Butalbital, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Higenamine interacts with.
In vitro research shows that higenamine inhibits CYP3A4 enzymes by 21%. However, 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 Fiorinal (aspirin, butalbital, and caffeine) and higenamine. The butalbital piece is partly broken down by a liver enzyme called CYP3A4. In a test-tube study, higenamine slowed that enzyme down a little (about 21%), which could in theory let butalbital build up slightly. More butalbital can mean extra drowsiness, dizziness, or feeling foggy. Keep in mind this is only lab data and has never been shown to happen in real people, so I wouldn't lose sleep over it.
I'm honestly more concerned about a different angle: both higenamine and the caffeine in Fiorinal are stimulants, so together they could nudge up your heart rate and blood pressure. Please run this combo by your pharmacist or doctor before mixing them.
- Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed
ANTICOAGULANT/ANTIPLATELET DRUGS
2 of 3Aspirin, Butalbital, Caffeine also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.
Animal research shows that higenamine inhibits platelet aggregation and reduces the size of thrombus formation.
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 to pay attention to: your Fiorinal contains aspirin, which already thins the blood a little by keeping platelets from clumping together. Higenamine, based mostly on animal studies, seems to do something similar. Put the two together and you could theoretically nudge up the odds of easy bruising, nosebleeds, bleeding gums, or a stomach bleed, since aspirin can also be hard on the stomach lining.
I want to be honest about the strength of this: it's a theoretical concern, not something proven in people. The bigger issue, frankly, is that higenamine is an unregulated stimulant with shaky labeling. Before you mix it with Fiorinal, please run it by your pharmacist or doctor first.
- Yun-Choi HS, Pyo MK, Park KM, et al. Anti-thrombotic effects of higenamine. Planta Med 2001;67:619-22. PubMed
STIMULANT DRUGS
3 of 3Aspirin, Butalbital, Caffeine also falls under STIMULANT DRUGS.
Higenamine has stimulant effects due to agonist activity at beta2-adrenoreceptors. In cardiac muscle, higenamine appears to have a positive inotropic effect and increase heart rate. However, it does not appear to increase blood pressure.
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.
The piece of Fiorinal that matters here is the caffeine. Caffeine is a stimulant, and higenamine acts a bit like adrenaline on your heart. Stacking two stimulant-type substances together can theoretically add up, so you might notice a faster or pounding heartbeat, jitteriness, or feeling wired. I want to be honest with you though: this concern is based on how these compounds work on paper, not on solid human studies, so it's a possible risk rather than a proven one.
One extra catch is that higenamine products are often mislabeled, so you may be getting more than the bottle claims. If you have any heart issues or high blood pressure, please run this combination by your pharmacist or doctor before mixing them.
- Wagner H, Reiter M, Ferstl W. New drugs with cardiotonic activity. Part 1. Chemistry and pharmacology of the cardiotonic active principle of Annona squamosa L. Planta Med 1980;40:77-85.
- Park CW, Chang KC, Lim JK. Effects of higenamine on isolated heart adrenoceptor of rabbit. Arch Int Pharmacodyn Ther 1984;267:279-88.
- Liu WH, Zhou YP, Zeng GY. Effects of dl-demethylcoclaurine on experimental heart failure. Acta Pharm Sinica 1988;23:81-5.
- Zhang Z, Liu X, Tao Z, et al. Effects of higeramine on hemodynamics and its tolerability and safety, an experimental study. Zhonghua Yi Xue Za Zhi 2002;82:352-5.
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.
Higenamine Also Interacts With Other Medications
Higenamine has 892 moderate known drug interactions in our database — the Aspirin, 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 Higenamine
We haven’t checked that one against Higenamine yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Higenamine. Pick one to open its full report.
See Every Supplement That Interacts With Aspirin, Butalbital, Caffeine
This page covers Higenamine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine page lists 347 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), Danshen (major) and Ephedra (major).
By severity: 13 major · 285 moderate · 49 minor.
From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine page
“The aspirin inside Fiorinal (aspirin, butalbital, caffeine) is the reason this list deserves careful reading rather than a quick skim. More than 200 of the supplements and herbs on file can thin the blood further and raise bleeding risk on top of aspirin's own antiplatelet effect, and even ordinary alcohol, beer and wine included, carr…”
Reviewed by 2 · Jul 18, 2026
Taking Higenamine as Part of a Dietary Supplement Product? Check It for Interactions
We hold 154 real supplement products containing Higenamine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Higenamine. Your product may carry other ingredients that interact with Aspirin, Butalbital, Caffeine too, on top of Higenamine — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Higenamine and Aspirin, 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.
#407 of 1,452 supplements looked up here in the last 7 days
#150 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 Higenamine
What is Higenamine?
- Weight loss and fat burning
- Pre-workout energy and performance
- Appetite suppression
- Athletic stimulant
- Traditional medicine remedies
Higenamine is a plant-based stimulant compound added to many weight-loss and pre-workout supplements, but there is very little human evidence that it works and real concerns about heart and blood pressure effects. It is banned in sports by the World Anti-Doping Agency (WADA), and product labels often list inaccurate amounts, so most people should approach it with caution and talk to a pharmacist or doctor first.
About Aspirin, Butalbital, and Caffeine
What Is Aspirin, Butalbital, and Caffeine Used For?
Brand name: Fiorinal
This combination is used to relieve the symptoms of tension (or muscle contraction) headache. The supported product is the oral capsule.
There is no evidence that it works or is safe for multiple recurrent headaches. Caution is needed because butalbital is habit-forming and can be abused.
Other Drugs & Higenamine
Browse every other medication we’ve checked against Higenamine — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
892 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Phentermine ›
- Aspirin ›
- Hydrocortisone ›
- Methylphenidate ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Phenylpropanolamine ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Nicotine ›
- Oxybutynin ›
- Oxycodone ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Miconazole ›
- Morphine Sulfate ›
- Phenylephrine ›
- Pseudoephedrine ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Diethylpropion ›
- Everolimus ›
- Ivabradine ›
- Ketoprofen ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Nortriptyline ›
- Propoxyphene ›
- Rifampin ›
Showing 60 of 892 moderate interactions — see all 892 on the Higenamine page.
No interaction 1,937 drugs checked — show the list
We also checked Higenamine against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Ivermectin ›
- Acetaminophen ›
- Rosuvastatin ›
- Isotretinoin ›
- Tirzepatide ›
- Levothyroxine, Liothyronine ›
- Docusate ›
- Metformin ›
- Valacyclovir ›
- Hydroxyurea ›
- Semaglutide ›
- Sumatriptan ›
- Methotrexate ›
- Lisinopril ›
- Amoxicillin ›
- Bupropion ›
- Azithromycin ›
- Pregabalin ›
- Doxycycline ›
- Gabapentin ›
- Bendamustine ›
- Lamotrigine ›
- Acyclovir ›
- Methylene Blue ›
- Ciprofloxacin ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Atenolol, Chlorthalidone ›
- Enalapril Maleate ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Canagliflozin, Metformin ›
- Ezetimibe ›
- Cephalexin ›
- Sacubitril, Valsartan ›
- Cyclopentolate ›
- Levetiracetam ›
- Levodopa ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Rosiglitazone Maleate ›
- Daunorubicin, Cytarabine ›
- Carbidopa, Levodopa ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Sulfamethoxazole, Trimethoprim ›
- Thyroid Hormone ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Bupivacaine, Meloxicam ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Mannitol ›
- Alginic Acid, Aluminum Hydroxide ›
- Efgartigimod Alfa-fcab ›
- Valsartan ›
- Insulin Aspart, Insulin Degludec ›
- Sodium Bicarbonate (otc Drug) ›
- Acarbose ›
- Measles, Mumps, Rubella Virus Live ›
- Peginterferon Alfa-2a, Ribavirin ›
- Spironolactone ›
Showing the 60 most looked-up of 1,937 medications checked with no known interaction — see the full Higenamine 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
Aspirin, Butalbital, Caffeine Is Linked to Lower Levels of 4 Nutrients
Natural Medicines records Aspirin, Butalbital, Caffeine as a medicine that can lower these. This is not an interaction with Higenamine — 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 Aspirin, 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 Higenamine and Aspirin, Butalbital, Caffeine Together: Common Questions
Can you take Higenamine with Aspirin, Butalbital, Caffeine?
Why are there 3 interactions listed for Higenamine and Aspirin, Butalbital, Caffeine?
How serious is the Higenamine and Aspirin, 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.