Drug & supplement interaction

Berberine + Dextromethorphan HBr, Phenylephrine HCl

Dextromethorphan HBr, Phenylephrine HCl brand name: Vicks Formula 44D Cough & Head Congestion Relief.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Dextromethorphan HBr, Phenylephrine HCl 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 Dextromethorphan HBr, Phenylephrine HCl

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. Dextromethorphan HBr, Phenylephrine HCl 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 Dextromethorphan HBr, Phenylephrine HCl

Dextromethorphan HBr, Phenylephrine HCl 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

Here's the gist for this cough and congestion combo: your body relies on a liver enzyme called CYP2D6 to break down the dextromethorphan part. Berberine may slow that enzyme down a bit, so the dextromethorphan could hang around longer than usual and build up. That might mean more of its typical side effects, like dizziness, drowsiness, nausea, or feeling a little foggy or unsteady.

I want to be honest about the strength of this: it's mostly theoretical, based on lab work and some early human data, not strong proof. For most folks taking a short course of cough medicine, it's unlikely to be a big deal. Still, since you're combining the two, it's worth a quick chat with your pharmacist to be safe.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Dextromethorphan HBr, Phenylephrine HCl 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

Here's the gist: berberine can mildly slow down a liver enzyme called CYP3A4, which is one of the pathways that helps your body break down the dextromethorphan in this cough and congestion product. If that enzyme is working slower, a little more dextromethorphan can hang around in your system than usual. In practice that might mean more of its typical effects, like drowsiness, dizziness, or feeling foggy.

That said, this is mostly a theoretical concern based on lab and early studies, and a short course of an over-the-counter cough product usually isn't a big deal. Still, if you take berberine daily, it's worth a quick chat with your pharmacist before combining them, especially if you notice extra sleepiness or lightheadedness.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Here's the gist with this cough and congestion product. Your body relies on a liver enzyme called CYP2D6 to break down the dextromethorphan (the cough suppressant) in it. Berberine appears to slow that enzyme down, so the dextromethorphan can hang around longer and build up. That may bump up its effects and side effects, things like drowsiness, dizziness, mild confusion, or nausea. The phenylephrine piece isn't really the concern here.

To be fair, this is based on early, lower quality research, so it's more of a 'keep an eye out' situation than a red alert. Still, if you're taking berberine regularly and reach for this medicine, it's worth a quick chat with your pharmacist before combining them, especially if you feel unusually groggy.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Dextromethorphan HBr, Phenylephrine HCl one above is among them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,158 No known interaction 1,671 (incl. Dextromethorphan HBr, Phenylephrine HCl)
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 Dextromethorphan HBr, Phenylephrine HCl

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 Dextromethorphan HBr, Phenylephrine HCl, 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 Dextromethorphan HBr, Phenylephrine HCl

This page covers Berberine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan HBr, Phenylephrine HCl page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Lithium (major) and Peyote (major).

By severity: 8 major · 148 moderate · 41 minor.

From our pharmacist’s overview on the Dextromethorphan HBr, Phenylephrine HCl page

“The supplement interactions with Dextromethorphan HBr and Phenylephrine HCl (Vicks Formula 44D) deserve real respect, and the small cluster of major-rated ones should be understood before you reach for the bottle. Phenylephrine is a stimulant-type decongestant, so anything with caffeine (coffee, tea, cola nut) or ephedrine-like herbs s…”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan HBr, Phenylephrine HCl 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 Dextromethorphan HBr, Phenylephrine HCl 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 Dextromethorphan HBr, Phenylephrine HCl 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 Dextromethorphan HBr, Phenylephrine HCl
Steady interest

#2,701 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
1 Major 1,158 Moderate 1,670 No 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

We also checked Berberine against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,670 medications checked with no known interaction — see the full Berberine list.

See the full Berberine interactions page
See every supplement checked against Dextromethorphan HBr, Phenylephrine HCl, ranked by severity
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

Keep exploring
Berberine monograph › Uses, safety, and every drug interaction in one place Dextromethorphan HBr, Phenylephrine HCl supplement interactions › Every supplement checked against Dextromethorphan HBr, Phenylephrine HCl, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Berberine and Dextromethorphan HBr, Phenylephrine HCl Together: Common Questions

Can you take Berberine with Dextromethorphan HBr, Phenylephrine HCl?
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 Dextromethorphan HBr, Phenylephrine HCl?
Dextromethorphan HBr, Phenylephrine HCl 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 Dextromethorphan HBr, Phenylephrine HCl 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

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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.