Drug & supplement interaction

Rue + Methotrexate

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

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Rue 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.

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Interaction report

Rue 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 Rue 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.

Rue safety at a glance

Rue overall Use caution Rue can be toxic in higher doses and the oil is especially risky, so use it cautiously if at all.
Pregnancy Likely Unsafe When used orally. Rue has uterine stimulant and abortifacient effects; avoid using. Deaths have been reported in women who used rue as an abortifacient. Read the full pregnancy detail
Breastfeeding Avoid Safety is not established and potentially toxic compounds may pass to the baby, so avoid use.

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.

Still wondering about combining Methotrexate and Rue? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

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. Rue has documented interactions with 1 drug class — the most serious being photosensitizing 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.

Keep it in perspective

Rue Does Interact With Other Medications

Rue has 335 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.

Moderate 335 No known interaction 2,495 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Rue

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

What to actually watch for

No Interaction Found — But Data Suggests Rue and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Seizures Worth acting on Additional detail

    Rue

    “Orally, therapeutic doses of rue can cause tremor, dizziness, drowsiness, sleep disorders, and depression. High doses can cause vertigo, seizures, and delirium (2,12,18).”

    Rue · Natural Medicines adverse-effect record, reported in depression.

    3 sources cited
    1. 2. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
    2. 12. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
    3. 18. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Drowsiness / Dizziness Additional detail

    Rue

    “Orally, rue is well tolerated when taken in the amounts found in foods. The dried herb seems to be generally well tolerated when taken in medicinal doses; however, a thorough evaluation of safety outcomes has not been conducted.”

    Rue · Natural Medicines adverse-effect record, reported in depression.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Itching Additional detail

    Rue

    “Topically, rue can cause contact dermatitis (2). Exposure to the fresh rue plant followed by sun exposure within 48 hours can lead to severe phototoxic reactions (2,6). Multiple case reports describe patients who developed pruritus, erythema, and severe blistering on the back of the hands and wrists, equivalent to a partial thickness burn, after contact with the fresh plant leaves and exposure to sunlight.”

    Rue · Natural Medicines adverse-effect record, reported in dermatitis.

    4 sources cited
    1. 2. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
    2. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    3. 104119. Radotra I, Gardiner S, Barnes D. A phytophototoxic injury at a burns unit: the ungraceful after-effects of the "common rue" plant. J Burn Care Res. 2018;39(6):1064-6. PubMed
    4. 107948. Avallone G, Mastorino L, Agostini A, et al. Ruta graveolens phytophotodermatitis. Dermatol Online J 2021;27(7). PubMed

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Stomach pain / Vomiting Additional detail

    Rue

    “Orally, rue can cause gastrointestinal irritation and cramps at therapeutic doses (2,12). When taken in large doses, it causes severe abdominal pain and vomiting (2,12,18).”

    Rue · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    3 sources cited
    1. 2. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
    2. 12. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
    3. 18. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • A skin rash Additional detail

    Rue

    Recorded for Rue in the same Natural Medicines adverse-effect record shown under Drowsiness / Dizziness above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

Reported for Rue but not commonly for Methotrexate: shortness of breath, trouble sleeping, low mood and confusion.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Rue come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Rue in Pregnancy & Breastfeeding

Pregnancy Likely Unsafe

When used orally. Rue has uterine stimulant and abortifacient effects; avoid using. Deaths have been reported in women who used rue as an abortifacient.

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

Overlapping uses

What Methotrexate Is Prescribed For, and What Rue Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Methotrexate is a prescription medicine with approved uses on its FDA label. Rue is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Methotrexate is prescribed for: 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.

Rue has been studied for:

  • Cancer studied, not established Rue has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Rue for cancer

    Although there has been interest in using oral rue for cancer, there is insufficient reliable information about the clinical effects of rue for this purpose.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Methotrexate on your own; if you are taking Rue for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Rue 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 Rue 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 Rue 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 Rue as Part of a Dietary Supplement Product? Check It for Interactions

We hold 47 real supplement products containing Rue, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Rue. Even though Rue 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:

How much people look this up

Where Rue 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 Rue
Steady interest

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

29 days ago today
Medication Methotrexate
Top 5%

#49 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.

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 Rue reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Rue and Methotrexate records this page draws on were last updated July 11, 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.
Data structure & sourcing designed and verified by .
Supplement

About Rue

What is Rue?

Rue
  • Menstrual cramps
  • Digestive upset
  • Muscle spasms and pain
  • Headache
  • Insect repellent (topical)
  • Traditional folk remedy

Rue is a strong-smelling herb from southern Europe with a long history in folk medicine, but there is very little reliable human research to support its health uses. It can be toxic in larger amounts and is considered unsafe during pregnancy, so most people should avoid it or use it only under professional guidance.

Ruta graveolens · Rutaceae · Aerial parts (leaves and flowering tops) and essential oil · Tea, tincture, dried herb, essential oil, topical preparations

An interaction check asks whether these two react with each other — it does not ask whether Rue is a good idea for someone in your situation. Here is what our Rue record says about it on its own.

Rue: dosing

There is no well-established or standardized safe dose of rue. Because the plant can be toxic and the amount of active compounds varies widely between products, it is hard to know what amount is safe.If you choose to use a commercial rue product, follow the directions on the label exactly and do not exceed them. The essential oil should not be taken internally.

From our Rue monograph — the full record covers uses, side effects and every documented interaction.

Read the full Rue 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.

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.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
Keep checking

Other Drugs & Rue

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

0Major
335Moderate
0Minor
2,494No known interaction
335 Moderate 2,494 No interaction
Moderate

335 interactions

Showing 60 of 335 moderate interactions — see all 335 on the Rue page.

No interaction 2,494 drugs checked — show the list

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

Showing the 60 most looked-up of 2,494 medications checked with no known interaction — see the full Rue list.

See the full Rue interactions page
See every supplement checked against Methotrexate, ranked by severity
Evidence & sources

Rue References

The 8 references that drive our Rue 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.

  1. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
  2. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  3. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  4. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.
  5. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  6. Puig L. Pharmacodynamic interaction with phototoxic plants during PUVA therapy. Br J Dermatol 1997;136:973-4. PubMed
  7. Radotra I, Gardiner S, Barnes D. A phytophototoxic injury at a burns unit: the ungraceful after-effects of the "common rue" plant. J Burn Care Res. 2018;39(6):1064-6. PubMed
  8. Avallone G, Mastorino L, Agostini A, et al. Ruta graveolens phytophotodermatitis. Dermatol Online J 2021;27(7). 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.

Pharmacist Counseling Corner

Taking Rue and Methotrexate Together: Common Questions

Is it safe to take Rue with Methotrexate?
We do not list a known interaction between Rue and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Rue and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 7 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Rue and Methotrexate used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Rue in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
How was the Rue and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Rue has documented interactions with 1 drug class — none of Methotrexate's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Rue interact with any other medications?
Yes. Rue has 335 documented drug interactions in our database — Methotrexate is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Rue is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

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

Where next

Keep Exploring

Rue monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, 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 References The 8 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Rue?

Our pharmacists answer your medication & supplement questions — free.

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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.