Drug & supplement interaction

Fennel + 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 Fennel can interact with; the most serious is rated moderate. Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.

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

Fennel and Acetaminophen, Aspirin, Caffeine

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

Why Are There 2 Interactions?

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

Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.

In vitro research suggests that fennel inhibits CYP3A4 enzyme activity. This effect has not been reported in humans.
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 practical takeaway for your Excedrin (acetaminophen, aspirin, and caffeine). Lab studies hint that fennel may slow down a liver enzyme called CYP3A4. In theory, slowing that enzyme could let a drug it processes build up a little. Of these three ingredients, caffeine is the one most affected by fennel's compounds, so you might feel slightly jittery, have a faster heartbeat, or have trouble sleeping. The aspirin and acetaminophen parts aren't really cleared this way.

The honest truth is this is only seen in test tubes, never in real people, so I wouldn't lose sleep over it. Food amounts of fennel almost certainly don't matter. If you take concentrated fennel supplements or the oil regularly, just mention it to your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  2. Subehan, Zaidi, S. F., Kadota, S., and Tezuka, Y. Inhibition on human liver cytochrome P450 3A4 by constituents of fennel (Foeniculum vulgare): identification and characterization of a mechanism-based inactivator. J Agric.Food Chem. 12-12-2007;55(25):101 PubMed
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

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

Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

Animal research suggests that fennel oil has antithrombotic and antiplatelet effects.
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 angle on this one. Excedrin contains aspirin, which is a blood thinner of sorts. It makes your platelets less sticky, so you bleed a little more easily. Fennel, at least in animal and lab studies, seems to nudge in the same direction by mildly discouraging clot formation. Stack the two and, in theory, you could add up to a slightly higher chance of bruising, nosebleeds, or stomach irritation that's slower to stop.

I'll be honest with you though: this is theoretical, based only on animal data, so I wouldn't lose sleep over it. Fennel sprinkled on food is no worry at all. Concentrated capsules or fennel oil are where I'd be a bit more cautious, especially if you take aspirin daily. A quick chat with your pharmacist or doctor settles it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Tognolini, M., Ballabeni, V., Bertoni, S., Bruni, R., Impicciatore, M., and Barocelli, E. Protective effect of Foeniculum vulgare essential oil and anethole in an experimental model of thrombosis. Pharmacol.Res 2007;56(3):254-260. PubMed
  2. Tognolini, M., Barocelli, E., Ballabeni, V., Bruni, R., Bianchi, A., Chiavarini, M., and Impicciatore, M. Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity. Life Sci. 2-23-2006;78(13):1419-1432. 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

Fennel Also Interacts With Other Medications

Fennel has 739 moderate 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 739 No known interaction 2,091 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Fennel

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

From our Q&A

Questions About Fennel 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 Fennel 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 Fennel 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 Fennel as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2,219 real supplement products containing Fennel, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Fennel. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Fennel — 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 Fennel 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 Fennel
Top 10%

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

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

#364 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 Fennel

What is Fennel?

Fennel
  • Digestive upset and bloating
  • Infant colic
  • Menstrual cramps
  • Cough and respiratory complaints
  • Breast milk support (traditional)

Fennel is a Mediterranean herb widely used as a food and spice, and traditionally taken for digestive complaints, colic, and menstrual cramps. Some small studies suggest possible benefit for certain stomach and menstrual symptoms, but the evidence is limited. It is generally well tolerated in food amounts, but concentrated supplements and the essential oil should be used with caution and after checking with your pharmacist or doctor.

Read the full Fennel monograph & all interactions
Keep checking

Other Drugs & Fennel

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

0Major
739Moderate
0Minor
2,090No known interaction
739 Moderate 2,090 No interaction
Moderate

739 interactions

Showing 60 of 739 moderate interactions — see all 739 on the Fennel page.

No interaction 2,090 drugs checked — show the list

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

Showing the 60 most looked-up of 2,090 medications checked with no known interaction — see the full Fennel list.

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

Can you take Fennel 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 Fennel and Acetaminophen, Aspirin, Caffeine?
Acetaminophen, Aspirin, Caffeine belongs to more than one drug category, and Fennel 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 Fennel 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.