Drug & supplement interaction

White Pepper + Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate brand name: Anacin w/ Codeine.

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

Aspirin, Caffeine, Codeine Phosphate falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

White Pepper and Aspirin, Caffeine, Codeine Phosphate

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

Why Are There 3 Interactions?

White Pepper interacts with whole categories of medication. Aspirin, Caffeine, Codeine Phosphate falls into 3 of those categories, so it can interact with White Pepper 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 Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate 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 key thing about this combo pill: the codeine part is a prodrug. Your body needs an enzyme called CYP2D6 to turn codeine into morphine, which is what actually relieves your pain. Lab studies hint that piperine, the spicy compound in white pepper, might gently block that same enzyme.

So in theory, lots of concentrated white pepper could mean less codeine gets converted to its active form, leaving you with weaker pain relief. The good news is this is only a theoretical concern based on test-tube data, not real patient cases. Ordinary cooking amounts of white pepper are very unlikely to matter. If you take pepper supplements regularly and notice your pain isn't well controlled, check in with your pharmacist or doctor.

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 3

Aspirin, Caffeine, Codeine Phosphate 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 thing to know about this combo pill: the codeine part is actually a prodrug. Your body has to convert it into morphine to get pain relief, and that conversion mostly relies on a different enzyme (CYP2D6), not CYP3A4. So the lab-based idea that piperine in white pepper blocks CYP3A4 doesn't translate into a big, predictable change here. If anything, CYP3A4 helps break codeine down into an inactive byproduct, so slowing it could leave a little more codeine around, with a small theoretical bump in drowsiness, constipation, or nausea.

Honestly, this is theoretical and based only on test-tube data. Normal kitchen amounts of white pepper are very unlikely to matter. If you take concentrated piperine supplements, just mention it to your pharmacist or doctor first.

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

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 3

Aspirin, Caffeine, Codeine Phosphate 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

This combination product already contains aspirin, which is a blood thinner that keeps your platelets from clumping together. Lab studies suggest that piperine, the spicy compound in white pepper, may also nudge platelets in that same anti-clotting direction. Stacked together, the theory is that they could add up and make bleeding or bruising a little more likely, on top of aspirin's usual chances of stomach upset or irritation.

Here's the reassuring part: this concern comes only from test-tube research, not from real people, and the white pepper you sprinkle on food is very unlikely to cause trouble. Concentrated piperine supplements are where I'd pump the brakes. If you take those and notice easy bruising, nosebleeds, or dark stools, loop in your pharmacist or doctor.

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 975 moderate, 3 minor known drug interactions in our database — the Aspirin, Caffeine, Codeine Phosphate 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. Aspirin, Caffeine, Codeine Phosphate)
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, Caffeine, Codeine Phosphate

This page covers White Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Codeine Phosphate page lists 398 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), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

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

“Anacin with Codeine combines aspirin, caffeine, and codeine, and each of the three picks up its own supplement problems, so this is a list worth real caution. Just over half of the 398 ingredients here, 202 of them, can add to aspirin's blood-thinning action and raise bleeding risk.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Codeine Phosphate 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, Caffeine, Codeine Phosphate 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, Caffeine, Codeine Phosphate 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

#1,212 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Aspirin, Caffeine, Codeine Phosphate
Top half

#1,408 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 Aspirin, Caffeine, Codeine Phosphate, 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, Caffeine, Codeine Phosphate supplement interactions › Every supplement checked against Aspirin, Caffeine, Codeine Phosphate, 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 Aspirin, Caffeine, Codeine Phosphate Together: Common Questions

Can you take White Pepper with Aspirin, Caffeine, Codeine Phosphate?
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 White Pepper and Aspirin, Caffeine, Codeine Phosphate?
Aspirin, Caffeine, Codeine Phosphate 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, Caffeine, Codeine Phosphate 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.