Drug & supplement interaction

Red Clover + Naproxen, Pseudoephedrine

Naproxen, Pseudoephedrine brand name: Aleve Cold and Sinus.

Minor Interaction
The bottom line Minor

Naproxen, Pseudoephedrine 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 Naproxen, Pseudoephedrine

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. Naproxen, Pseudoephedrine 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 Naproxen, Pseudoephedrine

Naproxen, Pseudoephedrine 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 on combining red clover with Aleve Cold and Sinus (which is naproxen plus pseudoephedrine). In the test tube, red clover's isoflavones can slow down a liver enzyme called CYP1A2, which plays a part in clearing some medicines. If that slowdown happened in real life, the worry would be slightly higher drug levels and a bit more side effects.

The good news: this is mostly a lab-bench finding. When researchers actually gave people red clover and tracked a CYP1A2 marker, they saw no real change. So a meaningful interaction here is unlikely. Still, naproxen alone can cause stomach upset and pseudoephedrine can raise blood pressure and heart rate, so it's always smart to run the combo past your pharmacist, especially if you have high blood pressure.

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

Naproxen, Pseudoephedrine 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 gist with Aleve Cold and Sinus (naproxen plus pseudoephedrine) and red clover. The naproxen part is handled by a liver enzyme called CYP2C9. In a test tube, red clover's plant compounds looked like they might slow that enzyme down a bit, which in theory could let naproxen build up slightly and nudge up side effects like stomach upset, heartburn, or, with regular use, a higher chance of bleeding or kidney strain.

The reassuring part: this is only lab evidence, and a small human study found red clover did not actually change how a similar CYP2C9 drug was cleared. So a real-world problem here is unlikely. Naproxen is not a prodrug, so it stays active either way. Still, if you use this combo often, it's worth a quick word with your pharmacist or doctor.

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

Naproxen, Pseudoephedrine 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 with Aleve Cold and Sinus (which combines naproxen, an anti-inflammatory pain reliever, with pseudoephedrine, a decongestant). The worry on file is that red clover might thin the blood a bit and add to naproxen's own tendency to irritate the stomach and raise bleeding risk. In theory, stacking the two could mean a little more bruising or stomach upset.

The good news: this is mostly lab-dish thinking. Real human studies, including ones lasting up to two years, found red clover did not actually change blood clotting. So for most folks this is a low concern. Still, since naproxen alone can cause stomach bleeding, mention any new supplement to your pharmacist, especially if you notice dark stools, easy bruising, or stomach pain.

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 Naproxen, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

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 Naproxen, Pseudoephedrine

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Naproxen, Pseudoephedrine page lists 334 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: 11 major · 279 moderate · 44 minor.

From our pharmacist’s overview on the Naproxen, Pseudoephedrine page

“Aleve Cold and Sinus pairs naproxen, an anti-inflammatory painkiller, with pseudoephedrine, a decongestant that acts as a mild stimulant, and that combination is why its supplement list runs to 334 entries and deserves real vigilance. The two biggest themes mirror the two drugs.”

Reviewed by 2 · Jul 18, 2026

Open the Naproxen, Pseudoephedrine 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 Naproxen, Pseudoephedrine 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 Naproxen, Pseudoephedrine 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 Naproxen, Pseudoephedrine
Steady interest

#1,758 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
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
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

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Pharmacist Counseling Corner

Taking Red Clover and Naproxen, Pseudoephedrine Together: Common Questions

Can you take Red Clover with Naproxen, Pseudoephedrine?
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 Naproxen, Pseudoephedrine?
Naproxen, Pseudoephedrine 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 Naproxen, Pseudoephedrine 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.