Drug & supplement interaction

Red Clover + Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen brand name: Combogesic.

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

Acetaminophen, Ibuprofen falls into 3 drug categories that Red Clover can interact with; the most serious is rated minor. Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Red Clover and Acetaminophen, Ibuprofen

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

Why Are There 3 Interactions?

Red Clover interacts with whole categories of medication. Acetaminophen, Ibuprofen falls into 3 of those categories, so it can interact with Red Clover in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Red Clover interacts with.

Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
In vitro evidence shows that red clover inhibits CYP1A2. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

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: this is a very minor, mostly theoretical concern. In a test tube, red clover's isoflavones can slow down a liver enzyme called CYP1A2. The thinking is that if that enzyme slows, certain drugs it processes could build up a bit. But when researchers actually tested red clover in people, it didn't meaningfully change how the body handled a CYP1A2 test substance.

For your Combogesic (acetaminophen plus ibuprofen), this matters even less. These two pain relievers aren't mainly cleared by CYP1A2, so red clover is very unlikely to boost them or cause extra effects like stomach upset or liver strain. I wouldn't lose sleep over it, but it's always smart to run your supplement list past your pharmacist, especially with red clover's hormone-like activity.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Acetaminophen, Ibuprofen also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.
In vitro evidence suggests that red clover might inhibit CYP2C9. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

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: this one barely registers. In a lab dish, red clover's plant isoflavones looked like they might slow down CYP2C9, an enzyme that helps clear the ibuprofen part of Combogesic. In theory, slowing that enzyme could let ibuprofen build up a little, which might mean more of its usual effects like stomach upset, heartburn, or, with regular use, kidney strain. The acetaminophen half isn't really handled by this pathway.

But when researchers actually tested red clover capsules in people, they saw no real change in how a CYP2C9 drug was processed. So this stays theoretical and unlikely. If you take Combogesic often or have stomach or kidney concerns, just give your pharmacist or doctor a quick heads-up before adding red clover.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 3

Acetaminophen, Ibuprofen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Although some laboratory research suggests that red clover may have anticoagulant and antiplatelet activity, clinical research has not shown this effect.
In vitro research suggests that genistein in red clover has antiplatelet effects, and historically, red clover was thought to have anticoagulant effects due to its coumarin content. However, some experts state that this is unlikely as most natural coumarins have not been shown to have anticoagulant effects, and their content in red clover is low. Additionally, some clinical research in postmenopausal patients found no effect on coagulation or prothrombin time with the use of red clover flowering tops 378 mg daily for 12 months or red clover isoflavone (Rimostil) 50 mg daily for 2 years.
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 gist: lab studies hinted that red clover might thin the blood a little, partly because of its isoflavones (like genistein) and small amounts of coumarins. The one ingredient in your Combogesic that overlaps here is the ibuprofen, which on its own can mildly affect platelets and irritate the stomach. So in theory, stacking them could nudge up bleeding or bruising risk.

In real life, though, this worry hasn't held up. Human studies giving red clover for many months found no meaningful change in clotting. So this is a minor, mostly theoretical concern. I'd just keep an eye out for easy bruising, nosebleeds, or stomach upset, and check with your pharmacist or doctor before adding red clover, especially if you take it daily.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009;16:1156-66. PubMed
  2. Guerrero JA, Lozano ML, Castillo J, et al. Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost 2005;3(2):369-376. PubMed
  3. Kondo K, Suzuki Y, Ikeda Y, Umemura K. Genistein, an isoflavone included in soy, inhibits thrombotic vessel occlusion in the mouse femoral artery and in vitro platelet aggregation. Eur J Pharmacol 2002;455(1):53-57. PubMed
  4. Polini N, Rauschemberger MB, Mendiberri J, et al. Effect of genistein and raloxifene on vascular dependent platelet aggregation. Mol Cell Endocrinol 2007;267(1-2):55-62. PubMed
  5. Clifton-Bligh PB, et al. Red cover isoflavones enriched with formononetin lower serum LDL cholesterol- a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2015;69(1):134-142.

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

Red Clover Also Interacts With Other Medications

Red Clover has 44 moderate, 822 minor known drug interactions in our database — the Acetaminophen, Ibuprofen one above is among them. If you take anything else, check it against the full list below.

Moderate 44 Minor 822 No known interaction 1,964 (incl. Acetaminophen, Ibuprofen)
Taking anything else?

Check Another of Your Medications Against Red Clover

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Ibuprofen

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Ibuprofen page lists 342 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 Piracetam (major).

By severity: 7 major · 290 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Ibuprofen page

“Combogesic pairs acetaminophen with ibuprofen, so it inherits the vulnerabilities of both drugs, and its supplement list deserves real attention before you add anything to it. Of the 342 ingredients on file, 7 carry a major rating, and those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Ibuprofen interaction page

One more smart check

Taking Red Clover as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Acetaminophen, Ibuprofen too, on top of Red Clover — 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 Red Clover and Acetaminophen, Ibuprofen 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 Red Clover
Top 25%

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

29 days ago today
Medication Acetaminophen, Ibuprofen
Top 25%

#410 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 Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Keep checking

Other Drugs & Red Clover

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

0Major
44Moderate
822Minor
1,963No known interaction
44 Moderate 822 Minor 1,963 No interaction
Moderate

44 interactions

Minor

822 interactions

Showing 60 of 822 minor interactions — see all 822 on the Red Clover page.

No interaction 1,963 drugs checked — show the list

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

Showing the 60 most looked-up of 1,963 medications checked with no known interaction — see the full Red Clover list.

See the full Red Clover interactions page
See every supplement checked against Acetaminophen, Ibuprofen, 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
Red Clover monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Ibuprofen supplement interactions › Every supplement checked against Acetaminophen, Ibuprofen, 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 Red Clover and Acetaminophen, Ibuprofen Together: Common Questions

Can you take Red Clover with Acetaminophen, Ibuprofen?
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.
Why are there 3 interactions listed for Red Clover and Acetaminophen, Ibuprofen?
Acetaminophen, Ibuprofen belongs to more than one drug category, and Red Clover 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 Red Clover and Acetaminophen, Ibuprofen 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

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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.