Drug & supplement interaction

Comfrey + Methotrexate

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

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

Comfrey has a moderate interaction with Methotrexate. Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.

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

Comfrey and Methotrexate

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

Moderate

HEPATOTOXIC DRUGS

Why this applies to Methotrexate

Methotrexate falls under HEPATOTOXIC DRUGS — the group Comfrey interacts with.

Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.
Due to its pyrrolizidine alkaloid constituents, comfrey can cause hepatotoxic effects, including ascites, cirrhosis, hepatic fibrosis, hepatomegaly, and sinusoidal obstruction syndrome.
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 concern with these two together: methotrexate is already known to be tough on the liver, especially when you take it regularly for psoriasis or rheumatoid arthritis. Comfrey contains natural compounds called pyrrolizidine alkaloids that can also harm the liver, particularly when swallowed. Stacking two liver stressors could, in theory, add up and raise your risk of liver trouble (things like scarring, fluid buildup, or rising liver enzymes).

To be fair, this is a theoretical warning based on how each works, not proof from studies pairing them. Still, with methotrexate I'd play it very safe. Oral comfrey really shouldn't be used by anyone. If you're using a comfrey skin product, please check with your pharmacist or doctor first, and don't stop your methotrexate on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Food and Drug Administration. FDA Advises Dietary Supplement Manufacturers to Remove Comfrey Products From the Market. July 6, 2001. Available at: http://www.cfsan.fda.gov/~dms/dspltr06.html.
  2. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. 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

Comfrey Also Interacts With Other Medications

Comfrey has 439 moderate 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.

Moderate 439 No known interaction 2,391 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Comfrey

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

From our Q&A

Questions About Comfrey 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 Comfrey 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 Comfrey 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

Open the Methotrexate interaction page

One more smart check

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

We hold 29 real supplement products containing Comfrey, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Comfrey. Your product may carry other ingredients that interact with Methotrexate too, on top of Comfrey — 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 Comfrey 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 Comfrey
Top half

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

29 days ago today
Medication Methotrexate
Top 5%

#40 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 Comfrey

What is Comfrey?

Comfrey
  • Bruises and sprains
  • Muscle and joint pain
  • Minor wounds and skin irritation
  • Back pain
  • Inflammation

Comfrey is a traditional herb used mainly on the skin for bruises, sprains, and joint pain, and some topical products show modest benefit for these uses. However, comfrey contains compounds that can seriously damage the liver, so it should never be taken by mouth and should only be used on unbroken skin for short periods. Pregnant or breastfeeding people should avoid it entirely.

Read the full Comfrey monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats several kinds of cancer, plus rheumatoid arthritis, polyarticular juvenile idiopathic arthritis (pJIA, a form of arthritis in children that affects many joints), and severe psoriasis. Which uses apply depends on the specific product.

Methotrexate tablets, Trexall and Jylamvo (oral solution) are used for acute lymphoblastic leukemia (ALL), mycosis fungoides, relapsed or refractory non-Hodgkin lymphoma, rheumatoid arthritis, pJIA and severe psoriasis. Xatmep (oral solution) is only for ALL and pJIA in children. Methotrexate injection products cover a wider list of cancers. Otrexup and Rasuvo (subcutaneous auto-injectors) are for rheumatoid arthritis, pJIA and psoriasis only, and are not for cancer.

See full Methotrexate drug information
Keep checking

Other Drugs & Comfrey

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

0Major
439Moderate
0Minor
2,390No known interaction
439 Moderate 2,390 No interaction
Moderate

439 interactions

Showing 60 of 439 moderate interactions — see all 439 on the Comfrey page.

No interaction 2,390 drugs checked — show the list

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

Showing the 60 most looked-up of 2,390 medications checked with no known interaction — see the full Comfrey list.

See the full Comfrey 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
Comfrey 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 Comfrey and Methotrexate Together: Common Questions

Can you take Comfrey with Methotrexate?
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 Comfrey and Methotrexate 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 and Comfrey?

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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.