Horse Chestnut + Methotrexate
Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.
We found no known interaction between Horse Chestnut and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.
Horse Chestnut and Methotrexate
We checked these two against our interaction database. Here is what we found.
No Known Interaction Found
We did not find a documented interaction between Methotrexate and Horse Chestnut in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.
If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.
Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.
Horse Chestnut safety at a glance
Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.
Why No Interaction Is Listed for Methotrexate
Interactions in our licensed database are recorded against drug classes, not just single drug names. Methotrexate is filed under 6 classifications — including organic anion-transporting polypeptide substrates (oatp), organic anion transporter 3 (oat3) substrates, hepatotoxic drugs. Horse Chestnut has documented interactions with 1 drug class — the most serious being anticoagulant/antiplatelet drugs (moderate) — and none of Methotrexate’s classifications are among them.
Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.
Horse Chestnut Does Interact With Other Medications
Horse Chestnut has 122 moderate known drug interactions in our database — Methotrexate isn’t one of them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Horse Chestnut
We haven’t checked that one against Horse Chestnut yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Horse Chestnut. Pick one to open its full report.
Horse Chestnut in Pregnancy & Breastfeeding
When the raw seed, bark, flower, or leaf are used orally. Horse chestnut preparations can be lethal; avoid using. There is insufficient reliable information available about the safety of horse chestnut seed extract when used during pregnancy and lactation; avoid using.
DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center
Questions About Horse Chestnut or Methotrexate
These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Horse Chestnut or Methotrexate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:
- Supplements for Leg Circulation Safe With Citalopram and Lisinopril ›
- Black Currant Oil With Levothyroxine, Methotrexate, and a Statin ›
- Bergamot With Methotrexate Interaction Question ›
- Can You Take Berberine With Methotrexate? ›
Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.
See Every Supplement That Interacts With Methotrexate
This page covers Horse Chestnut only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate 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).
By severity: 7 major · 60 moderate · 15 minor.
From our pharmacist’s overview on the Methotrexate page
“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”
Reviewed by 2 · Jul 18, 2026
Taking Horse Chestnut as Part of a Dietary Supplement Product? Check It for Interactions
We hold 487 real supplement products containing Horse Chestnut, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Horse Chestnut. Even though Horse Chestnut itself has no known interaction with Methotrexate, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:
Where Horse Chestnut and Methotrexate 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.
#281 of 1,452 supplements looked up here in the last 7 days
#49 of 2,830 medications looked up here in the last 7 days
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.
Where does our data come from?
- Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
- Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Horse Chestnut reference on this page ↓
- Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Horse Chestnut and Methotrexate records this page draws on were last updated July 10, 2026.
- What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
About Horse Chestnut
What is Horse Chestnut?
- Chronic venous insufficiency
- Leg swelling and heaviness
- Varicose veins
- Hemorrhoids
- Bruising and minor swelling
Horse chestnut seed extract is most often used for chronic venous insufficiency, where standardized products may help reduce leg swelling, pain, and heaviness. Raw, unprocessed horse chestnut seeds and other parts of the plant are toxic and should never be eaten. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.
Aesculus hippocastanum · Sapindaceae · Seeds (extract), and sometimes bark and leaves · Capsules, tablets, standardized seed extracts, topical gels and creams
An interaction check asks whether these two react with each other — it does not ask whether Horse Chestnut is a good idea for someone in your situation. Here is what our Horse Chestnut record says about it on its own.
Horse Chestnut: dosing
There is no single official dose for horse chestnut. Products are usually standardized to their aescin (escin) content, and the right amount depends on the specific product.The best approach is to follow the directions on the product label and choose a reputable, standardized extract.
From our Horse Chestnut monograph — the full record covers uses, side effects and every documented interaction.
About Methotrexate
What Is Methotrexate Used For?
Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex
Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).
Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.
Most-Reported Side Effects for Methotrexate
From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.
Other Drugs & Horse Chestnut
Browse every other medication we’ve checked against Horse Chestnut — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
122 interactions
- Diclofenac Sodium ›
- Ibuprofen ›
- Aspirin ›
- Naproxen ›
- Minocycline ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Ketoprofen ›
- Bivalirudin ›
- Warfarin Sodium ›
- Bromfenac Sodium ›
- Dabigatran ›
- Diclofenac Epolamine ›
- Iloprost ›
- Piroxicam ›
- Streptokinase ›
- Ticlopidine ›
- Treprostinil (oral) ›
- Abciximab ›
- Abrocitinib ›
- Acenocoumarol ›
- Acetylsalicylic Acid ›
- Anacaulase-bcdb ›
- Anagrelide ›
- Anisindione ›
- Antithrombin Iii ›
- Apixaban ›
- Argatroban ›
- Betrixaban ›
- Cablivi ›
- Cangrelor ›
- Cilostazol ›
- Clopidogrel ›
- Dalteparin ›
- Danaparoid ›
- Defibrotide Sodium ›
- Diclofenac ›
- Dicumarol ›
- Edoxaban ›
- Effient ›
- Enoxaparin ›
- Eptifibatide ›
- Fish Oil Triglycerides ›
- Fondaparinux ›
- Heparin ›
- Ibrutinib ›
- Ibuprofen Lysine ›
- Icosapent Ethyl (prescription Drug) ›
- Inotersen ›
- Lepirudin ›
- Nadroparin ›
- Naproxen Sodium ›
- Nintedanib Esylate ›
- Nusinersen Sodium ›
- Omega-3 Fatty Acids (prescription Drug) ›
- Pazopanib ›
- Pentoxifylline ›
- Phenprocoumon ›
- Reteplase ›
- Rivaroxaban ›
Showing 60 of 122 moderate interactions — see all 122 on the Horse Chestnut page.
No interaction 2,707 drugs checked — show the list
We also checked Horse Chestnut against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Amlodipine ›
- Methylphenidate ›
- Sertraline ›
- Testosterone ›
- Losartan Potassium ›
- Metoprolol ›
- Ivermectin ›
- Rosuvastatin ›
- Escitalopram ›
- Tadalafil ›
- Acetaminophen ›
- Valacyclovir ›
- Atorvastatin ›
- Docusate ›
- Hydroxyurea ›
- Abemaciclib ›
- Methamphetamine ›
- Sumatriptan ›
- Semaglutide ›
- Tirzepatide ›
- Prednisone ›
- Propranolol ›
- Lisdexamfetamine ›
- Acyclovir ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Bendamustine ›
- Amitriptyline ›
- Doxycycline ›
- Lamotrigine ›
- Fluoxetine ›
- Acetaminophen, Codeine ›
- Gabapentin ›
- Amphetamine ›
- Pregabalin ›
- Isotretinoin ›
- Dextroamphetamine ›
- Azithromycin ›
- Clonazepam ›
- Quetiapine ›
- Omeprazole ›
- Amlodipine Besylate ›
- Methylene Blue ›
- Duloxetine ›
- Letrozole ›
- Buspirone ›
- Citalopram ›
- Ciprofloxacin ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Acetaminophen, Oxycodone ›
- Dapsone ›
- Diazepam ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
Showing the 60 most looked-up of 2,707 medications checked with no known interaction — see the full Horse Chestnut list.
Horse Chestnut References
The 21 references that drive our Horse Chestnut monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.
- Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
- Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
- Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
- Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
- Greeske K, Pohlmann BK. Horse chestnut seed extract-an effective therapy principle in general practice. Drug therapy of chronic venous insufficiency. Fortschr Med 1996;114:196-200.
- Robbers JE, Tyler VE. Tyler's Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York, NY: The Haworth Herbal Press, 1999.
- Takegoshi K, Tohyama T, Okuda K, et al. A case of Venoplant-induced hepatic injury. Gastroenterol Jpn 1986;21:62-5.
- Jaspersen-Schib R, Theus L, Guirguis-Oeschger M, et al. [Serious plant poisonings in Switzerland 1966-1994. Case analysis from the Swiss Toxicology Information Center]. Schweiz Med Wochenschr 1996;126:1085-98.
- Popp W, Horak F, Jager S, et al. Horse chestnut (Aesculus hippocastanum) pollen: a frequent cause of allergic sensitization in urban children. Allergy 1992;47:380-3.
- Diaz-Perales A, Collada C, Blanco C, et al. Cross-reactions in the latex-fruit syndrome: A relevant role of chitinases but not of complex asparagine-linked glycans. J Allergy Clin Immunol 1999;104:681-7. PubMed
- Blanco C, Diaz-Perales A, Collada C, et al. Class I chitinases as potential panallergens involved in the latex-fruit syndrome. J Allergy Clin Immunol 1999;103:507-13. PubMed
- Comaish JS, Kersey PJ. Contact dermatitis to extract of horse chestnut (esculin). Contact Dermatitis 1980;6:150-1. PubMed
- Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd. PubMed
- Ottillinger, B. and Greeske, K. Rational therapy of chronic venous insufficiency--chances and limits of the therapeutic use of horse-chestnut seeds extract. BMC.Cardiovasc.Disord. 2001;1(1):5. PubMed
- Pittler, M. H. and Ernst, E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane.Database.Syst.Rev. 2004;(2):CD003230. PubMed
- Fang, Y., Zhao, L., Yan, F., Xia, X., Xu, D., and Cui, X. Escin improves sperm quality in male patients with varicocele-associated infertility. Phytomedicine. 2010;17(3-4):192-196. PubMed
- De Smet, P. A., Van den Eertwegh, A. J., Lesterhuis, W., and Stricker, B. H. Hepatotoxicity associated with herbal tablets. BMJ 7-13-1996;313(7049):92.
- Rehn, D., Unkauf, M., Klein, P., Jost, V., and Lucker, P. W. Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Arzneimittelforschung 1996;46(5):483-487.
- Edem E, Kahyaoglu B, Çakar MA. Acute Effusive Pericarditis due to Horse Chestnut Consumption. Am J Case Rep. 2016;17:305-8. PubMed
- Costa Santos D, Lérias G, Madruga I. Drug-induced Liver Injury Due to a Horse Chestnut Dietary Supplement. Eur J Case Rep Intern Med 2021;8(3):002389. PubMed
- Yi HY, Lee JY. Poisoning due to consumption of horse chestnut seed. Clin Exp Emerg Med 2021;8(4):333-335. PubMed
Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
Methotrexate Is Linked to Lower Levels of One Nutrient
Natural Medicines records Methotrexate as a medicine that can lower these. This is not an interaction with Horse Chestnut — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Methotrexate nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Horse Chestnut and Methotrexate Together: Common Questions
Is it safe to take Horse Chestnut with Methotrexate?
Do Horse Chestnut and Methotrexate have any of the same side effects?
How was the Horse Chestnut and Methotrexate combination checked?
Does Horse Chestnut interact with any other medications?
Does Methotrexate interact with any supplements?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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Still Have a Question About Methotrexate and Horse Chestnut?
Our pharmacists answer your medication & supplement questions — free.
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.