Drug & supplement interaction

Safflower + 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

Safflower has a moderate interaction with Acetaminophen, Aspirin, Caffeine. High doses of safflower oil might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.

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

Safflower and Acetaminophen, Aspirin, Caffeine

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

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Safflower interacts with.

High doses of safflower oil might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Small clinical studies show that taking safflower oil, approximately 55 grams daily for 2-3 weeks, decreases platelet aggregation. However, taking lower doses of safflower oil, such as 5 grams daily for 4 weeks, does not seem to affect platelet function. In one case report, a 74-year-old male stabilized on warfarin developed urinary tract bleeding and an elevated INR after taking a safflower extract 20 grams daily for 14 days.
Severity Moderate Likelihood Possible Evidence B

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 Excedrin: one of its three ingredients is aspirin, which already thins your blood a bit by making your platelets less sticky. High-dose safflower oil seems to do something similar. So when you stack them, the blood-thinning effect can add up, and that's where the concern comes from. In real life this could show up as easier bruising, nosebleeds, bleeding gums, or stomach upset and bleeding from the aspirin side.

The good news is that this mostly applies to concentrated supplement doses (think 20 to 55 grams a day). Normal safflower cooking oil on your food isn't likely to be an issue. The evidence here is modest, but if you take safflower supplements regularly, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Demke, D. M., Peters, G. R., Linet, O. I., Metzler, C. M., and Klott, K. A. Effects of a fish oil concentrate in patients with hypercholesterolemia. Atherosclerosis 1988;70(1-2):73-80. PubMed
  2. Kwon, J. S., Snook, J. T., Wardlaw, G. M., and Hwang, D. H. Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B2 formation, and fatty acid composition of platelet phospholipids. Am.J.Clin.Nutr. PubMed
  3. Challen, A. D., Branch, W. J., and Cummings, J. H. The effect of aspirin and linoleic acid on platelet aggregation, platelet fatty acid composition and haemostasis in man. Hum Nutr Clin Nutr 1983;37(3):197-208.
  4. Liu Y, Liu S, Shi Y, et al. Effects of safflower injection on the pharmacodynamics and pharmacokinetics of warfarin in rats. Xenobiotica. 2017 Oct 25:1-6. [Epub ahead of print] 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

Safflower Also Interacts With Other Medications

Safflower has 207 moderate 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 207 No known interaction 2,623 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Safflower

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

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

We hold 276 real supplement products containing Safflower, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Safflower. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Safflower — 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 Safflower 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 Safflower
Top half

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

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

#377 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 Safflower

What is Safflower?

Safflower
  • Heart and cholesterol support
  • Skin moisturizing
  • Menstrual cramps
  • Mild constipation
  • Weight management (oil)

Safflower is a thistle-like plant used mainly for its seed oil (a common cooking oil) and its colorful flowers. Safflower oil is a reasonable source of unsaturated fats, but strong proof that supplements treat specific diseases is limited. The flower extracts have much weaker evidence and should be used with caution, especially during pregnancy.

Read the full Safflower monograph & all interactions
Keep checking

Other Drugs & Safflower

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

0Major
207Moderate
0Minor
2,622No known interaction
207 Moderate 2,622 No interaction
Moderate

207 interactions

Showing 60 of 207 moderate interactions — see all 207 on the Safflower page.

No interaction 2,622 drugs checked — show the list

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

Showing the 60 most looked-up of 2,622 medications checked with no known interaction — see the full Safflower list.

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

Can you take Safflower 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.
How serious is the Safflower 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

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

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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.