Goldenseal + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.
Acetaminophen, Chlorpheniramine, Codeine, 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, Chlorpheniramine, Codeine, 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, Chlorpheniramine, Codeine, 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, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, 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 Colrex combo already has two ingredients that can make you drowsy: codeine (an opioid cough/pain reliever) and chlorpheniramine (a sedating antihistamine). Goldenseal contains a compound called berberine, and in animal studies berberine showed mild sedative effects of its own. So the worry here is simple addition: stacking goldenseal on top of these ingredients could, in theory, leave you feeling sleepier, foggier, or more slowed down than usual.
I'll be honest with you, this is a theoretical concern. The extra sleepiness has been seen in animals, not reported in people, so it's far from certain. Still, if you notice more grogginess or trouble concentrating, that's worth knowing. Don't drive until you see how you feel, and 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, Chlorpheniramine, Codeine, 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..
This combo product contains codeine, and that is the piece to pay attention to here. Codeine is a prodrug, meaning your body has to convert it into morphine using an enzyme called CYP2D6 before it can really relieve your cough or pain. Goldenseal can block that same enzyme. So instead of building codeine up, goldenseal would likely leave you making less active morphine, which may mean weaker cough or pain relief.
The evidence that goldenseal slows CYP2D6 is fairly solid, though it comes from lower-quality studies. Everyday cooking amounts aren't the concern; concentrated supplement capsules are. If you take goldenseal regularly, mention it to your pharmacist or doctor before relying on this product for relief.
- 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, Chlorpheniramine, Codeine, 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 combination product (sold as Colrex) has several pieces, but the one to watch with goldenseal is the codeine. Goldenseal tends to slow down a liver enzyme called CYP3A4. Codeine is partly handled by that pathway, so blocking it can let more codeine linger in your body than expected. That may mean more of codeine's usual effects, like drowsiness, dizziness, constipation, nausea, or in larger amounts slowed breathing.
The evidence here is moderate and based on small studies, so it is a possible concern rather than a sure thing. Everyday food amounts are not the issue; concentrated goldenseal supplements are. Please don't change anything on your own. Check with your pharmacist or doctor before pairing the two, especially since this product already causes sleepiness.
- 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, Chlorpheniramine, Codeine, 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 combo product (Colrex) bundles four ingredients, and the one that matters most for the goldenseal question is the acetaminophen. Acetaminophen is partly handled by a liver enzyme called CYP2E1. In test-tube studies, goldenseal's berberine seemed to slow that enzyme down a bit. On paper, slowing CYP2E1 could shift how acetaminophen is processed, but here's the important part: this has only been seen in lab dishes, never confirmed in real people.
For most folks taking normal doses, this is a theoretical concern, not something that's been shown to cause harm. The bigger everyday issue with acetaminophen is simply not exceeding the daily limit, especially if you drink alcohol. If you take goldenseal regularly, just mention it to your pharmacist or doctor so they 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, Chlorpheniramine, Codeine, 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, Chlorpheniramine, Codeine, Phenylephrine
This page covers Goldenseal only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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: 18 major · 275 moderate · 45 minor.
From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page
“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Chlorpheniramine, Codeine, 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, Chlorpheniramine, Codeine, 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, Chlorpheniramine, Codeine, 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.
#133 of 1,452 supplements looked up here in the last 7 days
#699 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 ›
- Docusate ›
- Hydroxyurea ›
- Valacyclovir ›
- Sumatriptan ›
- Amoxicillin ›
- Isotretinoin ›
- Methotrexate ›
- Bendamustine ›
- Bupropion ›
- Acyclovir ›
- Azithromycin ›
- Levothyroxine, Liothyronine ›
- Methylene Blue ›
- Ciprofloxacin ›
- Amoxicillin, Clavulanate Potassium ›
- Cephalexin ›
- Cyclopentolate ›
- Roxithromycin ›
- Ezetimibe ›
- Carbidopa, Levodopa ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Thyroid Hormone ›
- Pizotifen ›
- Levodopa ›
- Daptomycin ›
- Hexobarbitone ›
- Mitomycin ›
- Lenvatinib ›
- Cefaclor ›
- Magnesium Hydroxide (otc Drug) ›
- Pegunigalsidase Alfa-iwxj ›
- Flutemetamol F-18 ›
- Bentoquatam ›
- Factor 7a ›
- Alglucosidase Alpha ›
- Salbutamol Sulfate ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Phenylephrine ›
- Vancomycin ›
- Tocainide ›
- Hydroxychloroquine ›
- Bleomycin ›
- Ribavirin Aerosol ›
- Casanthranol, Docusate ›
- Rocuronium ›
- Ropinirole ›
- Procainamide ›
- Isoniazid, Pyrazinamide, Rifampin ›
- Alginic Acid, Aluminum Hydroxide ›
- Triptorelin ›
- Desflurane ›
- Choline Magnesium Trisalicylate ›
- Dirithromycin ›
- Benzocaine/menthol ›
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, Chlorpheniramine, Codeine, Phenylephrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Chlorpheniramine, Codeine, 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:
Read the full Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Goldenseal and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions
Can you take Goldenseal with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
Why are there 4 interactions listed for Goldenseal and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
How serious is the Goldenseal and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine and Goldenseal?
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