Drug & supplement interaction

Berberine + Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine brand names: Tylenol Cold Ex Strength, Children's Tylenol Cold Plus Cough.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine falls into 3 drug categories that Berberine can interact with; the most serious is rated moderate. Theoretically, berberine might increase serum levels of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Berberine and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Berberine interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine falls into 3 of those categories, so it can interact with Berberine in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Berberine interacts with.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, use of berberine with drugs metabolized by CYP2D6 might increase drug levels and increase the risk of adverse effects.
Severity Moderate Likelihood Possible Evidence B

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combination cold medicine has a few ingredients, but the one that matters here is dextromethorphan (the cough suppressant). Your body clears it using an enzyme called CYP2D6, and berberine may slow that enzyme down. In theory, that could let dextromethorphan build up a bit, which might mean more drowsiness, dizziness, or feeling foggy than usual. The other ingredients (acetaminophen, chlorpheniramine, and pseudoephedrine) aren't really affected this way.

I want to be honest that this is mostly theoretical, based on lab work and limited human data, so it's not something to panic over. Still, if you take berberine regularly, it's worth a quick chat with your pharmacist before reaching for this cold medicine, especially if you notice extra grogginess.

References
  1. 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
  2. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  3. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, use of berberine with drugs metabolized by CYP3A4 might increase drug levels and increase the risk of adverse effects.
Severity Moderate Likelihood Possible Evidence A

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This cold and cough combo has several ingredients, and the one that matters most here is dextromethorphan (the cough suppressant). Berberine appears to mildly slow down CYP3A4, one of the liver enzymes that helps clear dextromethorphan. In theory, that could let a bit more of it linger in your system, which might mean more drowsiness, dizziness, or a foggy, lightheaded feeling.

Honestly, for occasional short-term cold relief, this is usually a minor concern, and the evidence here is mostly theoretical and from lab work. The acetaminophen, chlorpheniramine, and pseudoephedrine parts aren't strongly affected by this pathway. Just don't double up on acetaminophen from other products, and check with your pharmacist if you take berberine daily.

References
  1. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  2. 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
  3. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  4. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
Moderate

DEXTROMETHORPHAN (Robitussin DM, others)

3 of 3
Theoretically, berberine may increase serum levels of dextromethorphan.
Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan. This may increase the effects and side effects of dextromethorphan.
Severity Moderate Likelihood Possible Evidence B

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This cold-and-cough combo includes dextromethorphan, the cough suppressant, and that's the piece berberine may affect. Your body clears dextromethorphan using a liver enzyme called CYP2D6. Berberine appears to slow that enzyme down, so the dextromethorphan can build up a bit higher than usual. The research behind this is early and modest in quality, so it's a possible concern rather than a sure thing.

If levels do climb, you might notice more drowsiness, dizziness, or feeling foggy. Pairing that with the chlorpheniramine (already a sedating antihistamine) could make the sleepiness stack up. The acetaminophen and pseudoephedrine aren't really part of this interaction. If you take berberine regularly and reach for this product, just run it by your pharmacist or doctor first.

References
  1. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • 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.
Evidence the quality of the studies behind the rating (graded A–D)
  • 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.

Keep it in perspective

Berberine Also Interacts With Other Medications

Berberine has 1 major, 1,158 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Berberine

Covers the 2,830 medications we’ve checked against Berberine. Pick one to open its full report.

From our Q&A

Questions About Berberine or Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Berberine or Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine

This page covers Berberine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine page lists 301 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), Ephedra (major) and Grapefruit (major).

By severity: 14 major · 242 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine page

“Because Tylenol Cold Extra Strength packs four drugs into one dose (acetaminophen, chlorpheniramine, dextromethorphan, and pseudoephedrine), its supplement list runs to 301 ingredients, and 14 carry a major rating, so I'd approach this one with real care. The biggest hazards mirror the drugs themselves.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction page

One more smart check

Taking Berberine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 908 real supplement products containing Berberine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Berberine. Your product may carry other ingredients that interact with Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine too, on top of Berberine — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Berberine and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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.

Supplement Berberine
Top 10%

#115 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine
Top 25%

#555 of 2,830 medications looked up here in the last 7 days

29 days ago today

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.

Supplement

About Berberine

What is Berberine?

Berberine
  • Blood sugar control
  • High cholesterol
  • Heart and metabolic health
  • Digestive upset
  • Antimicrobial support
  • Weight management

Berberine is a yellow plant compound that has shown promise for lowering blood sugar and cholesterol in some studies, but the quality of research varies and it is not a replacement for prescribed medicine. It can cause stomach upset and should be avoided during pregnancy and breastfeeding. Always check with your pharmacist or doctor before starting it, especially if you take other medications.

Read the full Berberine monograph & all interactions
Keep checking

Other Drugs & Berberine

Browse every other medication we’ve checked against Berberine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

1Major
1,158Moderate
0Minor
1,670No known interaction
Major

1 interaction

Moderate

1,158 interactions

Showing 60 of 1,158 moderate interactions — see all 1,158 on the Berberine page.

No interaction 1,670 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

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

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Pharmacist Counseling Corner

Taking Berberine and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine Together: Common Questions

Can you take Berberine with Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Berberine and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine?
Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine belongs to more than one drug category, and Berberine interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Berberine and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine and Berberine?

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