Higenamine + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 of drugs metabolized by CYP2D6.
Read the full interaction reportHigenamine and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
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. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 2D6 (CYP2D6) SUBSTRATES
1 of 3Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 this combination product: one of its ingredients, hydrocodone, is a prodrug. Your body uses an enzyme called CYP2D6 to turn it into hydromorphone, the form that actually relieves pain. Lab studies (only in test tubes, not in real people) suggest higenamine may block CYP2D6. If that happened in the body, less hydrocodone would be converted, so you might get weaker pain relief than expected.
On top of that, higenamine acts like adrenaline and can raise heart rate and blood pressure, and this product already contains caffeine and phenylephrine, which do the same thing. That stacking is my bigger real-world concern. Please check with your pharmacist or doctor before combining 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
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 3Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 deal with combining higenamine and this combo product (which includes hydrocodone, an opioid, plus a decongestant, antihistamine, caffeine, and acetaminophen). In lab dishes, higenamine slightly blocked the CYP3A4 enzyme, the same one your body uses to clear hydrocodone. In theory, that could let hydrocodone build up a bit, nudging up effects like drowsiness, slowed breathing, constipation, or dizziness. But this was only a 21% effect in a test tube and has never been shown in people, so I'd call it more of a yellow flag than a real alarm.
What concerns me more is the overlap of stimulants. Higenamine, caffeine, and phenylephrine can all raise heart rate and blood pressure, so together you might feel jittery, racing, or anxious. Please run this past your pharmacist or doctor first.
- 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
STIMULANT DRUGS
3 of 3Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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's the thing to watch with this combo product: it already contains two stimulants of its own, caffeine and phenylephrine. Higenamine is also a stimulant that acts on the same adrenaline-type receptors that can speed up your heart. Stacking it on top of the caffeine and phenylephrine here could, in theory, add up and put more strain on your heart, leaving you with a racing or pounding heartbeat, jitters, or a fluttering feeling in your chest.
I'll be honest that this concern is theoretical, based on how these ingredients work rather than on solid human studies, so it's not a reason to panic. Higenamine doesn't seem to push blood pressure up much. Still, since this medicine is for short-term cold and pain relief, I'd skip the higenamine supplement while taking it and check with your pharmacist first.
- 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Higenamine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page
“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.
#408 of 1,452 supplements looked up here in the last 7 days
#443 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 ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Acyclovir ›
- Bendamustine ›
- 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 ›
- Valsartan ›
- Levothyroxine Sodium ›
- Levetiracetam ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Phentermine, Topiramate ›
- Cefaclor ›
- Lenvatinib ›
- Vancomycin ›
- Dirithromycin ›
- Bentoquatam ›
- Pentobarbitone ›
- Amoxicillin, Clavulanate Potassium ›
- Procainamide ›
- Hydroxychloroquine ›
- Digoxin ›
- Azelaic Acid ›
- Triptorelin ›
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
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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:
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 Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Higenamine with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 3 interactions listed for Higenamine and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Higenamine and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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.