Drug & supplement interaction

Red Clover + Methotrexate Sodium

Methotrexate Sodium brand name: Xatmep.

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

Red Clover has a moderate interaction with Methotrexate Sodium. Theoretically, red clover might increase the risk of methotrexate toxicity.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Red Clover and Methotrexate Sodium

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

Moderate

METHOTREXATE (Trexall, others)

Theoretically, red clover might increase the risk of methotrexate toxicity.
In a case report, a 52-year-old female receiving weekly methotrexate injections for psoriasis developed symptoms of methotrexate toxicity, including severe vomiting and epigastric pain, after three days of taking red clover 430 mg daily. Toxicity resolved after red clover was discontinued. However, no liver function tests or methotrexate levels were reported.
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 situation with red clover and your methotrexate. Methotrexate isn't a prodrug; it works as-is, and it has a pretty narrow safety window, meaning even small shifts in how much stays in your body can tip you from a helpful dose into a toxic one. The concern here is that red clover might raise methotrexate levels and make side effects worse, like mouth sores, nausea and vomiting, stomach pain, fatigue, or low blood counts.

I want to be straight with you: this is built on a single case report, with no lab tests confirming the levels, so the evidence is weak and largely theoretical. Still, because methotrexate is one of those drugs where I don't like taking chances, please loop in your pharmacist or doctor before pairing it with a red clover supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Orr A and Parker R. Red clover causing symptoms suggestive of methotrexate toxicity in a patient on high-dose methotrexate. Menopause Int. 2013;19(3):133-134. 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

Red Clover Also Interacts With Other Medications

Red Clover has 43 moderate, 823 minor known drug interactions in our database — the Methotrexate Sodium one above is one of them. If you take anything else, check it against the full list below.

Moderate 43 Minor 823 No known interaction 1,964 (incl. Methotrexate Sodium)
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 Methotrexate Sodium

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate Sodium page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

Open the Methotrexate Sodium 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 Methotrexate Sodium 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 Methotrexate Sodium 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%

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

29 days ago today
Medication Methotrexate Sodium
Steady interest

#1,522 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
43Moderate
823Minor
1,963No known interaction
43 Moderate 823 Minor 1,963 No interaction
Moderate

43 interactions

Minor

823 interactions

Showing 60 of 823 minor interactions — see all 823 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 Methotrexate Sodium, 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 Methotrexate Sodium supplement interactions › Every supplement checked against Methotrexate Sodium, 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 Methotrexate Sodium Together: Common Questions

Can you take Red Clover with Methotrexate Sodium?
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 Red Clover and Methotrexate Sodium 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 Methotrexate Sodium and Red Clover?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.