Goldenseal + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 4 drug categories that Goldenseal can interact with; the most serious is rated moderate. Theoretically, goldenseal might increase the sedative effects of CNS depressants.
Read the full interaction reportGoldenseal and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Goldenseal interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 4 of those categories, so it can interact with Goldenseal in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 4Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CNS DEPRESSANTS — the group Goldenseal interacts with.
Goldenseal contains berberine. Animal research shows that berberine can have sedative effects. 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.
This combination product (Hycomine Compound) already has two ingredients that can make you drowsy: the opioid hydrocodone and the antihistamine chlorpheniramine. Goldenseal contains berberine, and in animal studies berberine showed some sedative effects. So the concern here is mostly theoretical: on paper, adding goldenseal might pile onto that sleepiness.
I want to be honest with you, though. This sedation effect has only been seen in animals, not reported in people, so the evidence is weak. Still, if you notice extra grogginess, dizziness, or slowed thinking, that is worth paying attention to, especially before driving. The caffeine and phenylephrine in this product work the other way and can offset some drowsiness. Check with your pharmacist or doctor before combining them.
- Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
- Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
- Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
- Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 4Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
Clinical and in vitro research shows that goldenseal can significantly inhibit CYP2D6 enzymes, potentially increasing levels of drugs metabolized by CYP2D6.
Interaction 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..
Here's the wrinkle with this combo pill: the hydrocodone part is a bit of a special case. Hydrocodone is partly a prodrug that the liver's CYP2D6 enzyme converts into hydromorphone, a more potent painkiller. Goldenseal can block that enzyme. In theory, that means less of the drug gets turned into the strong form, so you might get less pain relief than expected.
The flip side is that chlorpheniramine, the antihistamine in here, is also handled by CYP2D6. Slowing its breakdown could leave more of it around, which may add to drowsiness, dry mouth, or dizziness. The evidence here is real but modest, so don't panic. Just run this past your pharmacist or doctor before combining them.
- Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
- Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
- Sevior, D. K., Hokkanen, J., Tolonen, A., Abass, K., Tursas, L., Pelkonen, O., and Ahokas, J. T. Rapid screening of commercially available herbal products for the inhibition of major human hepatic cytochrome P450 enzymes using the N-in-one cocktail. Xeno PubMed
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
3 of 4Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
Most clinical and in vitro research shows that goldenseal inhibits CYP3A4 enzyme activity and increases serum levels of CYP3A4 substrates, such as midazolam. However, in one small clinical study, goldenseal did not affect the levels of indinavir, a CYP3A4 substrate, in healthy volunteers. This is likely due to the fact that indinavir has a high oral bioavailability, making it an inadequate probe for CYP3A4 interactions and/or that it is primarily metabolized by hepatic CYP3A, while goldenseal has more potential to inhibit intestinal CYP3A enzyme activity. Both goldenseal extract and its isolated constituents berberine and hydrastine inhibit CYP3A, with hydrastine possibly having more inhibitory potential than berberine.
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.
This combo product is a mouthful, but the piece that matters most here is the hydrocodone. Goldenseal can slow down the CYP3A4 enzyme in your gut and liver, and hydrocodone leans on that very pathway. When you block it, more hydrocodone can hang around in your body. That can mean stronger sedation, more drowsiness, dizziness, constipation, and in larger amounts, slowed breathing, which is the part we worry about most with opioids.
The evidence here is moderate, not airtight, but I'd still treat it with respect since opioids leave little room for error. The chlorpheniramine in this product already causes drowsiness, so the sedation could stack up. Before mixing goldenseal with this medicine, please check with your pharmacist or doctor first.
- Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
- Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ. Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol 2003;43:1283-8.. PubMed
- Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
- Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
- Gurley BJ, et al. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activitiy In Vivo. Clin Pharmacol Ther. 2008;83(1):61-69.
- Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
- Nguyen JT, Tian DD, Tanna RS, et al. An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Ob
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
4 of 4Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
In vitro research shows that goldenseal root extract can inhibit the activity of CYP2E1. 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.
This combination product (sold as Hycomine Compound) packs in acetaminophen, caffeine, an antihistamine, a decongestant, and the opioid hydrocodone. The piece that connects to goldenseal here is acetaminophen. A liver enzyme called CYP2E1 turns a small amount of acetaminophen into a byproduct that can be hard on the liver. Lab studies suggest goldenseal may slow that enzyme down. In theory, that could shift how acetaminophen is handled, but here's the honest part: this has only been seen in test-tube and animal studies, not in real people.
So I wouldn't lose sleep over an occasional dose. The bigger everyday concern with this product is simply not doubling up on acetaminophen from other cold or pain medicines. If you take goldenseal regularly, just mention it to your pharmacist so we can keep an eye on things.
- Yamaura K, Shimada M, Nakayama N, Ueno K. Protective effects of goldenseal (Hydrastis canadensis L.) on acetaminophen-induced hepatotoxicity through inhibition of CYP2E1 in rats. Pharmacognosy Res. 2011;3(4):250-5. 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.
Goldenseal Also Interacts With Other Medications
Goldenseal has 1,235 moderate, 1 minor 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 Goldenseal
We haven’t checked that one against Goldenseal yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Goldenseal. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Goldenseal 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 Goldenseal as Part of a Dietary Supplement Product? Check It for Interactions
We hold 1,726 real supplement products containing Goldenseal, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Goldenseal. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Goldenseal — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Goldenseal 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.
#157 of 1,452 supplements looked up here in the last 7 days
#478 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 Goldenseal
What is Goldenseal?
- Digestive upset and diarrhea
- Colds and respiratory infections
- Sore throat and mouth sores
- Skin and eye irritation (topical/traditional)
- Antimicrobial support
Goldenseal is a popular North American herb that contains berberine, a compound studied for antimicrobial effects. However, strong human evidence for its many traditional uses is largely lacking, and it should be avoided during pregnancy and breastfeeding. Talk to a pharmacist or doctor before using it.
Other Drugs & Goldenseal
Browse every other medication we’ve checked against Goldenseal — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,235 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Diphenhydramine ›
- Aspirin ›
- Hydrocortisone ›
- Insulin (rdna) ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Guaifenesin ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Insulin (pork) ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Insulin (human) ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Acetaminophen ›
Showing 60 of 1,235 moderate interactions — see all 1,235 on the Goldenseal page.
1 interaction
No interaction 1,593 drugs checked — show the list
We also checked Goldenseal against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Rosuvastatin ›
- Escitalopram ›
- Valacyclovir ›
- Docusate ›
- Hydroxyurea ›
- Sumatriptan ›
- Acyclovir ›
- Bupropion ›
- Amoxicillin ›
- Bendamustine ›
- Methotrexate ›
- Isotretinoin ›
- Azithromycin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Mitomycin ›
- Cefaclor ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Ezetimibe ›
- Levodopa ›
- Vancomycin ›
- Phenylephrine ›
- Dirithromycin ›
- Procainamide ›
- Lenvatinib ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Bentoquatam ›
- Hydroxychloroquine ›
- Amoxicillin, Clavulanate Potassium ›
- Dextrothyroxine ›
- Triptorelin ›
- Lomustine ›
- Succimer ›
- Tocainide ›
- Rocuronium ›
- Halothane ›
- Mitomycin C ›
- Pizotifen ›
- Gestodene ›
- Chenodiol ›
- Niacin (prescription Drug) ›
- Desflurane ›
- Cabergoline ›
- Famotidine ›
- Thalidomide ›
- Metronidazole ›
Showing the 60 most looked-up of 1,593 medications checked with no known interaction — see the full Goldenseal 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 Goldenseal — 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 Goldenseal and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Goldenseal with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 4 interactions listed for Goldenseal and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Goldenseal and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Goldenseal?
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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.