Drug & supplement interaction

Siberian Cocklebur + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

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

Siberian Cocklebur has a major interaction with Methotrexate. Siberian cocklebur can adversely affect the liver.

Read the full interaction report
SeverityMajor
LikelihoodLikely
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Siberian Cocklebur and Methotrexate

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

Major

HEPATOTOXIC DRUGS

Why this applies to Methotrexate

Methotrexate falls under HEPATOTOXIC DRUGS — the group Siberian Cocklebur interacts with.

Siberian cocklebur can adversely affect the liver. It has been linked to many cases of hepatotoxicity and some cases of liver failure. Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage. Some of these drugs include acarbose (Precose, Prandase), amiodarone (Cordarone), atorvastatin (Lipitor), azathioprine (Imuran), carbamazepine (Tegretol), cerivastatin (Baycol), diclofenac (Voltaren), felbamate (Felbatol), fenofibrate (TriCor), fluvastatin (Lescol), gemfibrozil (Lopid), isoniazid, itraconazole, (Sporanox), ketoconazole (Nizoral), leflunomide (Arava), lovastatin (Mevacor), methotrexate (Rheumatrex), nevirapine (Viramune), niacin, nitrofurantoin (Macrodantin), pioglitazone (Actos), pravastatin (Pravachol), pyrazinamide, rifampin (Rifadin), ritonavir (Norvir), rosiglitazone (Avandia), simvastatin (Zocor), tacrine (Cognex), tamoxifen, terbinafine (Lamisil), valproic acid, and zileuton (Zyflo).
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the concern with pairing these two. Methotrexate is already one of the harder medicines on your liver, and regular blood tests to check your liver enzymes are a standard part of taking it. Siberian cocklebur has its own track record of liver harm, including reports of serious liver injury and even liver failure. Stack two things that stress the liver and you raise the odds of trouble more than either one alone.

This isn't about the drug building up or wearing off. It's about added strain on the same organ. Watch for warning signs like yellowing skin or eyes, dark urine, belly pain, nausea, or unusual tiredness. Please don't start cocklebur without talking to your doctor or pharmacist first, given how toxic this plant can be.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gurley ES, Rahman M, Hossain MJ, et al. Fatal outbreak from consuming Xanthium strumarium seedlings during time of food scarcity in northeastern Bangladesh. PLoS One 2010 Mar 18;5(3):e9756. PubMed
  2. Turgut M, Alhan CC, Gurgoze M, et al. Carboxyatractyloside poisoning in humans. Ann Trop Paediatr 2005;25(2):125-34. PubMed
  3. Karabiber H, Almis H, Selimoglu MA, Yakinci C, Yilmaz S. Xanthium strumarium poisoning requiring liver transplantation. J Pediatr Gastroenterol Nutr. 2014;58(1):e6-9.

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

Siberian Cocklebur Also Interacts With Other Medications

Siberian Cocklebur has 661 major, known drug interactions in our database — the Methotrexate one above is one of them. If you take anything else, check it against the full list below.

Major 661 No known interaction 2,169 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Siberian Cocklebur

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

From our Q&A

Questions About Siberian Cocklebur 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 Siberian Cocklebur 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:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Methotrexate

This page covers Siberian Cocklebur 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 Sweet Orange (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

Open the Methotrexate interaction page

One more smart check

Taking Siberian Cocklebur as Part of a Dietary Supplement Product? Check It for Interactions

We hold 84 real supplement products containing Siberian Cocklebur, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Siberian Cocklebur. Your product may carry other ingredients that interact with Methotrexate too, on top of Siberian Cocklebur — 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 Siberian Cocklebur 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.

Supplement Siberian Cocklebur
Top half

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

29 days ago today
Medication Methotrexate
Top 5%

#44 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 Siberian Cocklebur

What is Siberian Cocklebur?

  • Nasal congestion and sinus problems
  • Allergic rhinitis (hay fever)
  • Headache
  • Skin conditions and itching
  • Joint and muscle discomfort

Siberian cocklebur is a fruit used in traditional Chinese and other Asian herbal medicine, mainly for nasal congestion, sinus issues, and allergies. Human evidence is very limited, and the plant contains naturally toxic compounds that can cause serious poisoning, so it should only be used under expert guidance, if at all.

Read the full Siberian Cocklebur monograph & all interactions
Medication

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.

See full Methotrexate drug information
Keep checking

Other Drugs & Siberian Cocklebur

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

661Major
0Moderate
0Minor
2,168No known interaction
661 Major 2,168 No interaction
Major

661 interactions

Showing 60 of 661 major interactions — see all 661 on the Siberian Cocklebur page.

No interaction 2,168 drugs checked — show the list

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

Showing the 60 most looked-up of 2,168 medications checked with no known interaction — see the full Siberian Cocklebur list.

See the full Siberian Cocklebur interactions page
See every supplement checked against Methotrexate, 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
Siberian Cocklebur monograph › Uses, safety, and every drug interaction in one place Methotrexate supplement interactions › Every supplement checked against Methotrexate, ranked by severity Methotrexate drug information › The full plain-English guide to this medication 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 Siberian Cocklebur and Methotrexate Together: Common Questions

Can you take Siberian Cocklebur with Methotrexate?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Siberian Cocklebur and Methotrexate interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Methotrexate and Siberian Cocklebur?

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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.