Drug & supplement interaction

White Pepper + Aspirin, Butalbital, Caffeine

Aspirin, Butalbital, Caffeine brand name: Fiorinal.

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

Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine

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. Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine

Aspirin, Butalbital, Caffeine 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

Here's the deal with Fiorinal (aspirin, butalbital, and caffeine) and white pepper. The piperine in pepper has shown, in test-tube studies only, an ability to slow down a liver enzyme called CYP3A4. The butalbital part of Fiorinal is handled in part by this enzyme. So in theory, if that pathway gets slowed, butalbital could hang around a bit longer and feel stronger, meaning more drowsiness, dizziness, or that groggy, sluggish feeling.

That said, this is purely theoretical and based on lab work, not real people. Normal cooking amounts of white pepper on your food are very unlikely to cause any problem. I'd only pause for concentrated piperine supplements. If you're considering those, check with your pharmacist or doctor first.

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

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

Aspirin, Butalbital, Caffeine also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

In vitro evidence suggests that piperine, a constituent of white pepper, inhibits platelet aggregation. Theoretically, white pepper might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Some anticoagulant/antiplatelet drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), 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

The piece of Fiorinal that matters here is the aspirin. Aspirin already makes your platelets less sticky, which is how it thins the blood a bit. In test-tube studies, piperine (the spicy compound in white pepper) also seemed to slow platelets down. Put the two together and, at least in theory, you could nudge up your risk of bleeding or bruising more easily.

Here's the reassuring part: this is based only on lab research, not real people, so the evidence is weak. The pinch of white pepper on your dinner almost certainly won't cause trouble. The bigger question would be concentrated piperine supplements. If you take Fiorinal regularly or notice easy bruising, nosebleeds, or dark stools, check in with your pharmacist or doctor before adding any pepper supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Raghavendra, R. H. and Naidu, K. A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis. Prostaglandins Leukot.Essent.Fatty Acids 2009;81(1):73-78. 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

White Pepper Also Interacts With Other Medications

White Pepper has 976 moderate, 3 minor known drug interactions in our database — the Aspirin, Butalbital, Caffeine one above is among them. If you take anything else, check it against the full list below.

Moderate 976 Minor 3 No known interaction 1,851 (incl. Aspirin, Butalbital, Caffeine)
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 Aspirin, Butalbital, Caffeine

This page covers White Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine page lists 347 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 · 285 moderate · 49 minor.

From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine page

“The aspirin inside Fiorinal (aspirin, butalbital, caffeine) is the reason this list deserves careful reading rather than a quick skim. More than 200 of the supplements and herbs on file can thin the blood further and raise bleeding risk on top of aspirin's own antiplatelet effect, and even ordinary alcohol, beer and wine included, carr…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, 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.

Supplement White Pepper
Top half

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

29 days ago today
Medication Aspirin, Butalbital, Caffeine
Top 5%

#82 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
Medication

About Aspirin, Butalbital, and Caffeine

What Is Aspirin, Butalbital, and Caffeine Used For?

Brand name: Fiorinal

This combination is used to relieve the symptoms of tension (or muscle contraction) headache. The supported product is the oral capsule.

There is no evidence that it works or is safe for multiple recurrent headaches. Caution is needed because butalbital is habit-forming and can be abused.

See full Aspirin, Butalbital, and Caffeine drug information Butalbital, Aspirin, And Caffeine NDC codes and packages
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
976Moderate
3Minor
1,850No known interaction
976 Moderate 3 Minor 1,850 No interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the White Pepper page.

Minor

3 interactions

No interaction 1,850 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 1,850 medications checked with no known interaction — see the full White Pepper list.

See the full White Pepper interactions page
See every supplement checked against Aspirin, Butalbital, Caffeine, 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 Aspirin, Butalbital, Caffeine supplement interactions › Every supplement checked against Aspirin, Butalbital, Caffeine, ranked by severity Aspirin, Butalbital, and Caffeine drug information › The full plain-English guide to this medication Butalbital, Aspirin, And Caffeine NDC codes and packages › Every package, labeler and price in the FDA directory 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 Aspirin, Butalbital, Caffeine Together: Common Questions

Can you take White Pepper with Aspirin, Butalbital, Caffeine?
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 Aspirin, Butalbital, Caffeine?
Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine 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.