Drug & supplement interaction

White Pepper + Belladonna, Caffeine, Ergotamine, Pentobarbital

Belladonna, Caffeine, Ergotamine, Pentobarbital brand name: Micomp PB.

Moderate Interaction
The bottom line Moderate

Belladonna, Caffeine, Ergotamine, Pentobarbital falls into 2 drug categories that White Pepper can interact with; the most serious is rated moderate. In vitro evidence suggests that piperine, a constituent of white pepper, inhibits cytochrome P450 3A4 (CYP3A4).

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

White Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital

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. Belladonna, Caffeine, Ergotamine, Pentobarbital 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 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Belladonna, Caffeine, Ergotamine, Pentobarbital

Belladonna, Caffeine, Ergotamine, Pentobarbital falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group White Pepper interacts with.

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

This combination pill includes ergotamine, which your body clears mainly through an enzyme called CYP3A4. White pepper contains piperine, and in lab dish studies piperine can slow that enzyme down. In theory, that could let ergotamine build up a bit, raising the chance of side effects like nausea, tingling or coldness in your fingers and toes, leg cramps, or muscle pain. The caffeine in this product can also linger longer, which might mean more jitteriness or trouble sleeping.

Here's the reassuring part: this is only a theoretical concern based on test-tube data, not real patient cases. Normal cooking amounts of white pepper are very unlikely to cause trouble. Concentrated piperine supplements are the bigger question mark, so check with your pharmacist or doctor before adding one.

Moderate

PENTOBARBITAL (Nembutal)

2 of 2
In an animal model, the piperine constituent of white pepper increased pentobarbitone-induced sleeping time. It is not known if this occurs in humans or if this applies to other barbiturates or sedatives. Theoretically, combining white pepper and pentobarbital might increase the sedative effects of pentobarbital.
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

This combination product (Micomp PB) contains pentobarbital, a barbiturate that calms the nervous system, along with belladonna, caffeine, and ergotamine. The piece worth knowing about here is the pentobarbital. In one animal study, the piperine in white pepper made pentobarbital-induced sleep last longer, suggesting it could add to the drug's sedating effect. In theory, that might mean a little more drowsiness, grogginess, or a heavy, hard-to-shake sleepy feeling.

I want to be honest that this is theoretical and based only on animal data, so we do not know if it happens in people. Everyday seasoning amounts of white pepper are very unlikely to matter. If you are considering concentrated piperine supplements, check with your pharmacist or doctor first.

References
  1. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.

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 Belladonna, Caffeine, Ergotamine, Pentobarbital 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 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 Belladonna, Caffeine, Ergotamine, Pentobarbital

This page covers White Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Belladonna, Caffeine, Ergotamine, Pentobarbital page lists 290 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), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 15 major · 227 moderate · 48 minor.

From our pharmacist’s overview on the Belladonna, Caffeine, Ergotamine, Pentobarbital page

“People who take Micomp PB for migraines are often the same people reaching for an herbal sleep aid or a caffeinated energy product during a rough stretch, and with four drugs in one tablet (belladonna, caffeine, ergotamine, pentobarbital) nearly everything clashes with something. The 290 supplement ingredients on file here earn genuine…”

Reviewed by 2 · Jul 18, 2026

Open the Belladonna, Caffeine, Ergotamine, Pentobarbital 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 Belladonna, Caffeine, Ergotamine, Pentobarbital 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 Belladonna, Caffeine, Ergotamine, Pentobarbital 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
Top half

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

29 days ago today
Medication Belladonna, Caffeine, Ergotamine, Pentobarbital
Top 5%

#102 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
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.

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 White Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital Together: Common Questions

Can you take White Pepper with Belladonna, Caffeine, Ergotamine, Pentobarbital?
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 Belladonna, Caffeine, Ergotamine, Pentobarbital?
Belladonna, Caffeine, Ergotamine, Pentobarbital 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 Belladonna, Caffeine, Ergotamine, Pentobarbital 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.