Drug & supplement interaction

White Pepper + Dextromethorphan HBr, Guaifenesin

Dextromethorphan HBr, Guaifenesin brand names: Vicks Formula 44E Cough & Chest Congestion Relief, Pediatric Vicks Formula 44e Cough & Chest Congesti.

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

Dextromethorphan HBr, Guaifenesin falls into 2 drug categories that White Pepper can interact with; the most serious is rated moderate. In vitro evidence suggests that some constituents of white pepper inhibit cytochrome P450 2D6 (CYP2D6).

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

White Pepper and Dextromethorphan HBr, Guaifenesin

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

White Pepper interacts with whole categories of medication. Dextromethorphan HBr, Guaifenesin falls into 2 of those categories, so it can interact with White Pepper in 2 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 2

Why this applies to Dextromethorphan HBr, Guaifenesin

Dextromethorphan HBr, Guaifenesin falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group White Pepper interacts with.

In vitro evidence suggests that some constituents of white pepper inhibit cytochrome P450 2D6 (CYP2D6). Theoretically, concomitant use may affect drugs metabolized by CYP2D6.
Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.
Severity Moderate Likelihood Possible Evidence D

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 simple version. The dextromethorphan in this cough syrup is cleared from your body mainly by a liver enzyme called CYP2D6. Lab studies hint that piperine, a compound in white pepper, might mildly slow that same enzyme down. If that happened, dextromethorphan could linger a bit longer and feel a little stronger, meaning slightly more drowsiness, dizziness, or stomach upset for some folks. The guaifenesin part is not affected. Good news: this is only a theoretical concern from test-tube work, not real patient reports.

Sprinkling white pepper on your dinner is very unlikely to matter. Concentrated piperine supplements are a different story, so check with your pharmacist before combining those with cough medicine.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Dextromethorphan HBr, Guaifenesin also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

In vitro evidence suggests that piperine, a constituent of white pepper, inhibits cytochrome P450 3A4 (CYP3A4). Theoretically, concomitant use with white pepper might increase the effects and side effects of drugs metabolized by CYP3A4.
Some drugs metabolized by CYP3A4 include some calcium channel blockers (diltiazem, nicardipine, verapamil), chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), glucocorticoids, cisapride (Propulsid), alfentanil (Alfenta), fentanyl (Sublimaze), losartan (Cozaar), fluoxetine (Prozac), midazolam (Versed), omeprazole (Prilosec), ondansetron (Zofran), propranolol (Inderal), fexofenadine (Allegra), and numerous others.
Severity Moderate Likelihood Possible Evidence D

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 short version: the piperine in white pepper can mildly block an enzyme called CYP3A4, which is one of the pathways your body uses to break down dextromethorphan (the cough suppressant in this product). In theory, slowing that breakdown could let a little more dextromethorphan build up, which might mean more drowsiness, dizziness, or a foggy, lightheaded feeling. Guaifenesin, the mucus-thinning part, isn't really affected this way.

Honestly though, this is based on lab data only, not real people, and a sprinkle of white pepper on your food is very unlikely to cause a problem. If you're taking concentrated piperine supplements, just mention it to your pharmacist or doctor first.

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

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

White Pepper Also Interacts With Other Medications

White Pepper has 975 moderate, 3 minor known drug interactions in our database — the Dextromethorphan HBr, Guaifenesin one above is among them. If you take anything else, check it against the full list below.

Moderate 975 Minor 3 No known interaction 1,852 (incl. Dextromethorphan HBr, Guaifenesin)
Taking anything else?

Check Another of Your Medications Against White Pepper

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

Everything else you take

See Every Supplement That Interacts With Dextromethorphan HBr, Guaifenesin

This page covers White Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan HBr, Guaifenesin page lists 171 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), St. John's Wort (major) and 1,3-dmaa (moderate).

By severity: 4 major · 125 moderate · 42 minor.

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

“A bad cough tends to hit when supplements are already on the counter, and anyone reaching for Vicks Formula 44E (dextromethorphan HBr and guaifenesin) should treat this list with real care, since 4 of its 171 entries carry a major rating. Two themes dominate.”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan HBr, Guaifenesin interaction page

One more smart check

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

We hold 2 real supplement products containing White Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides White Pepper. Your product may carry other ingredients that interact with Dextromethorphan HBr, Guaifenesin too, on top of White Pepper — 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 White Pepper and Dextromethorphan HBr, Guaifenesin 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 White Pepper
Steady interest

#1,215 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Dextromethorphan HBr, Guaifenesin
Top half

#1,394 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 White Pepper

What is White Pepper?

  • Digestive upset
  • Seasoning and appetite support
  • Cough and cold remedies (traditional)
  • Minor aches and pains (traditional)
  • Antimicrobial (traditional)

White pepper comes from the same plant as black pepper and is mostly used as a kitchen spice. In normal food amounts it is generally safe for most people, but there is little solid human research supporting its use as a medicine. Talk with your pharmacist or doctor before using concentrated supplements, especially if you are pregnant, breastfeeding, or have a health condition.

Read the full White Pepper monograph & all interactions
Keep checking

Other Drugs & White Pepper

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

0Major
975Moderate
3Minor
1,851No known interaction
975 Moderate 3 Minor 1,851 No interaction
Moderate

975 interactions

Showing 60 of 975 moderate interactions — see all 975 on the White Pepper page.

Minor

3 interactions

No interaction 1,851 drugs checked — show the list

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

Showing the 60 most looked-up of 1,851 medications checked with no known interaction — see the full White Pepper list.

See the full White Pepper interactions page
See every supplement checked against Dextromethorphan HBr, Guaifenesin, 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
White Pepper monograph › Uses, safety, and every drug interaction in one place Dextromethorphan HBr, Guaifenesin supplement interactions › Every supplement checked against Dextromethorphan HBr, Guaifenesin, 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 White Pepper and Dextromethorphan HBr, Guaifenesin Together: Common Questions

Can you take White Pepper with Dextromethorphan HBr, Guaifenesin?
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 2 interactions listed for White Pepper and Dextromethorphan HBr, Guaifenesin?
Dextromethorphan HBr, Guaifenesin belongs to more than one drug category, and White Pepper 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 White Pepper and Dextromethorphan HBr, Guaifenesin 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.