Higenamine + Aspirin, Butalbital, Caffeine, Codeine Phosphate
Aspirin, Butalbital, Caffeine, Codeine Phosphate brand name: Fiorinal w/ Codeine.
Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 4 drug categories that Higenamine can interact with; the most serious is rated moderate. Theoretically, higenamine might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Read the full interaction reportHigenamine and Aspirin, Butalbital, Caffeine, Codeine Phosphate
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Higenamine interacts with whole categories of medication. Aspirin, Butalbital, Caffeine, Codeine Phosphate falls into 4 of those categories, so it can interact with Higenamine 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 Aspirin, Butalbital, Caffeine, Codeine Phosphate
Aspirin, Butalbital, Caffeine, Codeine Phosphate falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Higenamine interacts with.
In vitro research shows that higenamine inhibits CYP2D6 enzymes. 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 wrinkle with Fiorinal with Codeine: the codeine part is a prodrug. Your body has to switch it on using an enzyme called CYP2D6 before it gives you pain relief. Lab studies suggest higenamine may block that enzyme. If that happened in real life, less codeine would get turned into its active form, so you might get weaker pain relief than expected.
I'll be honest, this is only seen in test-tube research, not in actual people, so the worry is mostly theoretical. I'd also gently point out that higenamine itself is a heart and blood pressure stimulant, which isn't a great pairing with caffeine that's already in this product. Before mixing the two, please check with your pharmacist or doctor.
- 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
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 4Aspirin, Butalbital, Caffeine, Codeine Phosphate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
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 with Codeine. This combo pill contains butalbital, a barbiturate that your liver clears partly through an enzyme called CYP3A4. In a lab dish, higenamine slowed that same enzyme by about 21 percent. If that happened in real people, butalbital could build up a little, which might mean more drowsiness, dizziness, or feeling foggy and slowed down.
The honest part: this has only been seen in test-tube studies, never in actual patients, so I don't want to overstate it. There's a separate concern worth a mention too. Higenamine acts like adrenaline and can raise heart rate and blood pressure, and this product already has caffeine. Please check with your pharmacist or doctor before pairing 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
3 of 4Aspirin, Butalbital, Caffeine, Codeine Phosphate 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.
The piece of this combo pill that matters here is the aspirin. Aspirin is already a blood thinner that keeps your platelets from sticking together, so it can cause easier bruising, nosebleeds, or stomach irritation on its own. Lab and animal studies suggest higenamine may also slow platelet clumping, so stacking the two could, in theory, nudge your bleeding risk a little higher.
I want to be honest about the strength of this: it is theoretical, based on pharmacology and animal data, not solid human studies. Still, since higenamine doses on labels are often inaccurate and it can stress your heart and blood pressure, I'd run this past your pharmacist or doctor before combining them, and watch for unusual bruising, dark stools, or bleeding that won't stop.
- Yun-Choi HS, Pyo MK, Park KM, et al. Anti-thrombotic effects of higenamine. Planta Med 2001;67:619-22. PubMed
STIMULANT DRUGS
4 of 4Aspirin, Butalbital, Caffeine, Codeine Phosphate 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.
Here is the piece to focus on with Fiorinal with Codeine: it already contains caffeine, which is a stimulant. Higenamine acts a bit like adrenaline on your heart, nudging your heart rate up and giving it a stronger push. Stack that on top of the caffeine in this product, and you could feel more of the jittery, racing-heart, palpitation type effects. That is the theoretical concern here.
To be fair, this is a theoretical caution based on how higenamine works, not strong human proof, and the available data suggests it does not really raise blood pressure. Still, if you have any heart rhythm or blood pressure history, it is worth a quick chat with your pharmacist or doctor before pairing the two.
- 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 890 moderate known drug interactions in our database — the Aspirin, Butalbital, Caffeine, Codeine Phosphate 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, Codeine Phosphate
This page covers Higenamine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine, Codeine Phosphate page lists 398 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 Danshen (major).
By severity: 17 major · 334 moderate · 47 minor.
From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine, Codeine Phosphate page
“Fiorinal with Codeine packs four active drugs into one capsule, and I would treat its supplement list with genuine wariness rather than a quick skim. The aspirin component is why roughly half of the 398 ingredients on file raise bleeding risk, while the codeine and butalbital explain a second large cluster that deepens sedation, someti…”
Reviewed by 2 · Jul 18, 2026
Open the Aspirin, Butalbital, Caffeine, Codeine Phosphate interaction page
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, Codeine Phosphate 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, Codeine Phosphate 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.
#398 of 1,452 supplements looked up here in the last 7 days
#1,863 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.
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 “”.
890 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 890 moderate interactions — see all 890 on the Higenamine page.
No interaction 1,939 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 ›
- Rosuvastatin ›
- Escitalopram ›
- Acetaminophen ›
- Docusate ›
- Hydroxyurea ›
- Valacyclovir ›
- Semaglutide ›
- Sumatriptan ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Bendamustine ›
- Acyclovir ›
- Methotrexate ›
- Doxycycline ›
- Lamotrigine ›
- Pregabalin ›
- Gabapentin ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Mannitol ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Valsartan ›
- Hexobarbitone ›
- Levothyroxine Sodium ›
- Spironolactone ›
- Levetiracetam ›
- Phentermine, Topiramate ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Levodopa ›
- Mitomycin ›
- Minoxidil ›
- Lenvatinib ›
- Ezetimibe ›
- Cefaclor ›
- Vancomycin ›
- Bentoquatam ›
- Amoxicillin, Clavulanate Potassium ›
- Pentobarbitone ›
- Triptorelin ›
- Hydroxychloroquine ›
- Dirithromycin ›
- Pizotifen ›
- Digoxin ›
- Procainamide ›
Showing the 60 most looked-up of 1,939 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, Codeine Phosphate Is Linked to Lower Levels of 4 Nutrients
Natural Medicines records Aspirin, Butalbital, Caffeine, Codeine Phosphate 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, Codeine Phosphate 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, Codeine Phosphate Together: Common Questions
Can you take Higenamine with Aspirin, Butalbital, Caffeine, Codeine Phosphate?
Why are there 4 interactions listed for Higenamine and Aspirin, Butalbital, Caffeine, Codeine Phosphate?
How serious is the Higenamine and Aspirin, Butalbital, Caffeine, Codeine Phosphate interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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