Drug & supplement interaction

Indian Long Pepper + Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.

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

Acetaminophen, Aspirin, Caffeine falls into 2 drug categories that Indian Long Pepper can interact with; the most serious is rated moderate. Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.

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

Indian Long Pepper and Acetaminophen, Aspirin, Caffeine

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

Why Are There 2 Interactions?

Indian Long Pepper interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 2 of those categories, so it can interact with Indian Long 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 Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Indian Long Pepper interacts with.

Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4.
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 quick picture for this combo pill (acetaminophen, aspirin, and caffeine, like Excedrin). The piperine in Indian long pepper can mildly slow down a liver enzyme called CYP3A4 in lab studies. Of the three ingredients, caffeine is the one most likely to hang around a bit longer, so in theory you might feel more of caffeine's familiar effects: jitteriness, a racing heart, or trouble sleeping. None of these are prodrugs, so the spice isn't making them weaker.

Honestly, this is a theoretical concern based only on test-tube data, and a sprinkle of pepper in food is very unlikely to matter. Concentrated pippali supplements are more of a question mark. If you take it daily, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

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

Theoretically, Indian long pepper might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
In vitro research shows that Indian long pepper extract inhibits platelet aggregation.
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 product you're asking about (think Excedrin) is a combo of acetaminophen, aspirin, and caffeine. The piece that matters here is the aspirin, which already thins the blood a little by keeping platelets from clumping together. In lab studies, Indian long pepper appears to do something similar, so pairing the two could theoretically nudge your bleeding risk a bit higher.

Honestly, this is a weak, theory-level concern based only on test-tube research, not on real people, so I don't want to alarm you. Still, if you take this combo regularly and notice easy bruising, nosebleeds, or bleeding gums, mention it. And before adding a concentrated long pepper supplement, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yadav V, Krishnan A, Vohora D. A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research. J Ethnopharmacol. 2020;247:112255. 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

Indian Long Pepper Also Interacts With Other Medications

Indian Long Pepper has 892 moderate, 3 minor known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is among them. If you take anything else, check it against the full list below.

Moderate 892 Minor 3 No known interaction 1,935 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Indian Long Pepper

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Indian Long Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 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 · 312 moderate · 46 minor.

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

“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Aspirin, Caffeine interaction page

One more smart check

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

We hold 597 real supplement products containing Indian Long Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Long Pepper. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Indian Long 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 Indian Long Pepper and Acetaminophen, Aspirin, 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 Indian Long Pepper
Top 25%

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

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

#31 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 Indian Long Pepper

What is Indian Long Pepper?

Indian Long Pepper
  • Digestive upset
  • Respiratory and cough complaints
  • Boosting absorption of other supplements
  • Pain and inflammation
  • General wellness in Ayurveda

Indian long pepper (pippali) is a spice long used in Ayurvedic medicine and is best known for its piperine content, which may increase how well the body absorbs certain other substances. Modern human research on its health benefits is limited, so use it cautiously and let your pharmacist or doctor know if you take it regularly.

Read the full Indian Long Pepper monograph & all interactions
Keep checking

Other Drugs & Indian Long Pepper

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

0Major
892Moderate
3Minor
1,934No known interaction
892 Moderate 3 Minor 1,934 No interaction
Moderate

892 interactions

Showing 60 of 892 moderate interactions — see all 892 on the Indian Long Pepper page.

Minor

3 interactions

No interaction 1,934 drugs checked — show the list

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

Showing the 60 most looked-up of 1,934 medications checked with no known interaction — see the full Indian Long Pepper list.

See the full Indian Long Pepper interactions page
See every supplement checked against Acetaminophen, Aspirin, 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
Indian Long Pepper monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Aspirin, Caffeine supplement interactions › Every supplement checked against Acetaminophen, Aspirin, Caffeine, 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 Indian Long Pepper and Acetaminophen, Aspirin, Caffeine Together: Common Questions

Can you take Indian Long Pepper with Acetaminophen, Aspirin, 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 Indian Long Pepper and Acetaminophen, Aspirin, Caffeine?
Acetaminophen, Aspirin, Caffeine belongs to more than one drug category, and Indian Long 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 Indian Long Pepper and Acetaminophen, Aspirin, 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.