Drug & supplement interaction

Quercetin + Methotrexate Sodium

Methotrexate Sodium brand name: Xatmep.

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

Methotrexate Sodium falls into 2 drug categories that Quercetin can interact with; the most serious is rated moderate. Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.

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

Quercetin and Methotrexate Sodium

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

Why Are There 2 Interactions?

Quercetin interacts with whole categories of medication. Methotrexate Sodium falls into 2 of those categories, so it can interact with Quercetin in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ORGANIC ANION TRANSPORTER 3 (OAT3) SUBSTRATES

1 of 2

Why this applies to Methotrexate Sodium

Methotrexate Sodium falls under ORGANIC ANION TRANSPORTER 3 (OAT3) SUBSTRATES — the group Quercetin interacts with.

Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT3, with half-maximal inhibitory concentration (IC50) values as low as 0.75 mcM. So far, this interaction 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 gist with methotrexate and quercetin. Your kidneys use a transporter called OAT3 to help clear methotrexate out of your body. In lab (test tube) studies, quercetin appears to block that transporter. If it works the same way in people, less methotrexate would get flushed out, so more could build up and linger in your system.

Methotrexate is a drug where small changes really matter. Higher levels can mean more mouth sores, nausea, fatigue, low blood counts, or liver irritation. That said, this is only a theoretical concern from cell studies and hasn't actually been reported in people. Food amounts of quercetin are unlikely to be an issue, but before starting a high-dose supplement, please check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Li C, Wang X, Bi Y, et al. Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy. Toxicol Sci. 2020;175(2):279-291. PubMed
  2. Ni Y, Duan Z, Zhou D, et al. Identification of Structural Features for the Inhibition of OAT3-Mediated Uptake of Enalaprilat by Selected Drugs and Flavonoids. Front Pharmacol. 2020;11:802. PubMed
Moderate

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

2 of 2

Methotrexate Sodium also falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP).

Theoretically, concomitant use might increase the effects and adverse effects of OATP substrates.

In vitro evidence shows that quercetin can inhibit organic anion-transporting peptide (OATP) 1B1-mediated uptake of estrone-3-sulfate and pravastatin. Furthermore, clinical research in healthy males shows that intake of quercetin along with pravastatin increases the AUC of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.
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 gist: methotrexate gets moved around your body partly by transport proteins called OATPs. Quercetin, in lab and small human studies, can gently block these transporters. We saw this with another drug (pravastatin), where quercetin nudged blood levels up by a modest amount. The same idea could apply to methotrexate, meaning more of it might hang around than expected.

Why does that matter? Methotrexate is a drug where small shifts count. Higher levels can mean more mouth sores, nausea, fatigue, low blood counts, or liver and kidney strain. To be clear, this is mostly theoretical for methotrexate, and food amounts of quercetin are unlikely to be an issue. But before starting a high-dose supplement, please check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wu LX, Guo CX, Chen WQ, et al. Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment. Br J Clin Pharmacol 2012;73(5):750-7.

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

Quercetin Also Interacts With Other Medications

Quercetin has 1,168 moderate known drug interactions in our database — the Methotrexate Sodium one above is among them. If you take anything else, check it against the full list below.

Moderate 1,168 No known interaction 1,662 (incl. Methotrexate Sodium)
Taking anything else?

Check Another of Your Medications Against Quercetin

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

Everything else you take

See Every Supplement That Interacts With Methotrexate Sodium

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

We hold 4,589 real supplement products containing Quercetin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Quercetin. Your product may carry other ingredients that interact with Methotrexate Sodium too, on top of Quercetin — 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 Quercetin 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 Quercetin
Top 5%

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

29 days ago today
Medication Methotrexate Sodium
Steady interest

#1,612 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 Quercetin

What is Quercetin?

Quercetin
  • Seasonal allergies
  • Antioxidant support
  • Heart and blood pressure health
  • Anti-inflammatory support
  • Immune support
  • Exercise recovery

Quercetin is a plant flavonoid with antioxidant and anti-inflammatory properties found in many common foods and sold as a supplement. While early research is interesting for allergies, blood pressure, and inflammation, strong human evidence is limited for most uses. It is generally well tolerated in food amounts, but talk to your pharmacist or doctor before taking high-dose supplements.

Read the full Quercetin monograph & all interactions
Keep checking

Other Drugs & Quercetin

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

0Major
1,168Moderate
0Minor
1,661No known interaction
1,168 Moderate 1,661 No interaction
Moderate

1,168 interactions

Showing 60 of 1,168 moderate interactions — see all 1,168 on the Quercetin page.

No interaction 1,661 drugs checked — show the list

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

Showing the 60 most looked-up of 1,661 medications checked with no known interaction — see the full Quercetin list.

See the full Quercetin 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
Quercetin 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 Quercetin and Methotrexate Sodium Together: Common Questions

Can you take Quercetin 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.
Why are there 2 interactions listed for Quercetin and Methotrexate Sodium?
Methotrexate Sodium belongs to more than one drug category, and Quercetin 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 Quercetin 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

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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.