Drug & supplement interaction

Pomegranate + Acetaminophen, Aspirin, Caffeine

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

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

Pomegranate has a minor interaction with Acetaminophen, Aspirin, Caffeine. Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Pomegranate and Acetaminophen, Aspirin, Caffeine

Here is the interaction we found between these two, with the evidence behind it.

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Acetaminophen, Aspirin, Caffeine

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.
Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice. In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times; however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration. Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version for your Excedrin (the acetaminophen, aspirin, and caffeine combo): pomegranate is on file as something that could, in theory, slow down a liver enzyme called CYP3A4 and let certain drugs build up a bit. In the lab, pomegranate juice looked like it might block that enzyme, but when researchers actually tested it in people, drinking pomegranate juice did not meaningfully change drug levels. So the real-world concern here is very low.

On top of that, none of the three ingredients in Excedrin rely heavily on CYP3A4 to be cleared, so this interaction isn't a great match for this product anyway. Enjoying pomegranate as a fruit or juice alongside Excedrin is unlikely to cause stronger side effects like stomach upset or jitteriness. If you're using concentrated pomegranate extracts or take it often, just run it by your pharmacist to be safe.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos 2005;33:644-8. PubMed
  2. Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 2007;47:286-94. PubMed
  3. Yeo C, Shon J, Liu K, et al. The effects of pomegranate juice on the pharmacokinetics of simvastatin in healthy Korean subjects (PI-63). Clin Pharmacol Ther 2006;79:23.
  4. Farkas D, Greenblatt DJ. Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies. Expert Opin Drug Metab Toxicol 2008;4:381-93.
  5. Misaka S, Nakamura R, Uchida S, et al. Effect of 2 weeks' consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther PubMed
  6. Park SJ, Yeo CW, Shim EJ, et al. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects. Eur J Drug Metab Pharmacokinet 2016;41(4):339-44. 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

Pomegranate Also Interacts With Other Medications

Pomegranate has 355 moderate, 566 minor known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is one of them. If you take anything else, check it against the full list below.

Moderate 355 Minor 566 No known interaction 1,909 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Pomegranate

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

From our Q&A

Questions About Pomegranate or Acetaminophen, Aspirin, Caffeine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Pomegranate or Acetaminophen, Aspirin, Caffeine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Pomegranate 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 Pomegranate as Part of a Dietary Supplement Product? Check It for Interactions

We hold 4,607 real supplement products containing Pomegranate, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Pomegranate. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Pomegranate — 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 Pomegranate 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 Pomegranate
Top 5%

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

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 25%

#383 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 Pomegranate

What is Pomegranate?

Pomegranate
  • Heart and blood vessel health
  • Antioxidant support
  • High blood pressure
  • Inflammation
  • Digestive upset
  • Skin health

Pomegranate is a nutrient-rich fruit that is high in antioxidants and is widely enjoyed as food and juice. Early research suggests it may support heart health and blood pressure, but the evidence is still limited and not strong enough to call it a proven treatment. As a food it is generally safe, but talk to your pharmacist or doctor before using concentrated extracts, especially if you are pregnant, breastfeeding, or take medications.

Read the full Pomegranate monograph & all interactions
Keep checking

Other Drugs & Pomegranate

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

0Major
355Moderate
566Minor
1,908No known interaction
355 Moderate 566 Minor 1,908 No interaction
Moderate

355 interactions

Showing 60 of 355 moderate interactions — see all 355 on the Pomegranate page.

Minor

566 interactions

Showing 60 of 566 minor interactions — see all 566 on the Pomegranate page.

No interaction 1,908 drugs checked — show the list

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

Showing the 60 most looked-up of 1,908 medications checked with no known interaction — see the full Pomegranate list.

See the full Pomegranate 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
Pomegranate 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 Pomegranate and Acetaminophen, Aspirin, Caffeine Together: Common Questions

Can you take Pomegranate with Acetaminophen, Aspirin, Caffeine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Pomegranate and Acetaminophen, Aspirin, Caffeine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Aspirin, Caffeine and Pomegranate?

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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.