Goldenseal + Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.
Acetaminophen, Aspirin, Caffeine falls into 3 drug categories that Goldenseal can interact with; the most serious is rated moderate. Goldenseal might increase serum levels of drugs metabolized by CYP3A4.
Read the full interaction reportGoldenseal and Acetaminophen, Aspirin, Caffeine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Goldenseal interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 3 of those categories, so it can interact with Goldenseal 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 Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Goldenseal interacts with.
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.
Here's the thing with these combo headache tablets (acetaminophen, aspirin, and caffeine like in Excedrin): goldenseal is known to slow down a liver enzyme called CYP3A4. Of the three ingredients, caffeine is the one most affected here, so goldenseal could let caffeine linger longer in your system. That may mean more of caffeine's usual effects, like jitteriness, a racing or pounding heart, trouble sleeping, or feeling on edge.
For most healthy people taking an occasional dose, this is a fairly mild concern, and the evidence is moderate rather than rock-solid. Still, if you use goldenseal regularly or are sensitive to caffeine, it's worth a quick chat with your pharmacist or doctor before combining them.
- 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
ANTICOAGULANT/ANTIPLATELET DRUGS
2 of 3Acetaminophen, Aspirin, Caffeine also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.
Goldenseal contains berberine. In vitro and animal research shows that berberine can inhibit platelet aggregation. 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 piece that matters with Excedrin: one of its three ingredients is aspirin, which already thins your blood a bit by keeping platelets from clumping together. Goldenseal contains berberine, and in lab dishes and animal studies that compound seems to slow platelet clumping too. Stack the two and, in theory, you could nudge up your bleeding risk a little, think easier bruising, nosebleeds, or a cut that's slow to stop.
The honest part: this is theoretical only. It hasn't actually been seen in people, so I wouldn't lose sleep over it. The acetaminophen and caffeine in Excedrin aren't the concern here. Still, if you take blood thinners or use Excedrin often, run it past your pharmacist or doctor first.
- Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
- Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
3 of 3Acetaminophen, Aspirin, Caffeine 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.
Here's the piece that matters for this combo product (Excedrin Migraine). The acetaminophen part is handled in your liver partly by an enzyme called CYP2E1. Goldenseal has shown, in lab dish studies only, that it might slow that enzyme down. If that happened in people, acetaminophen could clear a bit slower and build up slightly. The reason this gets attention is that one of acetaminophen's breakdown steps through CYP2E1 can form a substance that's hard on the liver, so the picture isn't totally simple.
The honest bottom line: this has never actually been shown in humans, so it's theoretical and not a reason to panic. Still, since you're already getting acetaminophen plus aspirin and caffeine, I'd keep doses sensible and just run goldenseal by your pharmacist before pairing the two regularly.
- 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, Aspirin, Caffeine 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, Aspirin, Caffeine
This page covers Goldenseal only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 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 · 312 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Aspirin, Caffeine page
“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”
Reviewed by 2 · Jul 18, 2026
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, Aspirin, Caffeine 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, Aspirin, 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.
#157 of 1,452 supplements looked up here in the last 7 days
#383 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 ›
- Amoxicillin, Clavulanate Potassium ›
- Hydroxychloroquine ›
- 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, Aspirin, Caffeine Is Linked to Lower Levels of 5 Nutrients
Natural Medicines records Acetaminophen, Aspirin, Caffeine 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, Aspirin, 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 Goldenseal and Acetaminophen, Aspirin, Caffeine Together: Common Questions
Can you take Goldenseal with Acetaminophen, Aspirin, Caffeine?
Why are there 3 interactions listed for Goldenseal and Acetaminophen, Aspirin, Caffeine?
How serious is the Goldenseal and Acetaminophen, Aspirin, Caffeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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