Drug & supplement interaction

Blue Flag + 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 Blue Flag 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

Blue Flag 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 Blue Flag 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.

Blue Flag safety at a glance

Blue Flag overall Use caution The root, especially when fresh, can cause nausea, vomiting, and irritation, so it should be used cautiously.
Pregnancy Avoid Avoid during pregnancy because of potential toxicity and lack of safety data.
Breastfeeding Likely Unsafe When used orally; avoid using. Read the full breastfeeding detail

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 Blue Flag? 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. Blue Flag has documented interactions with 3 drug classes — the most serious being digoxin (lanoxin) (major), diuretic drugs (moderate) and warfarin (coumadin) (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

Blue Flag Does Interact With Other Medications

Blue Flag has 1 major, 77 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.

Major 1 Moderate 77 No known interaction 2,752 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Blue Flag

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

What to actually watch for

No Interaction Found — But Data Suggests Blue Flag 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.

  • Nausea / Vomiting reported in 5.9% of FDA reports for Methotrexate Additional detail

    Blue Flag

    “Orally, blue flag can cause nausea and vomiting, and the fresh root can irritate mucosa (4,19). Orally and topically, the volatile oil constituent of blue flag irritates mucous membranes and can cause lacrimation, eye inflammation, irritation of the throat, and headache (4).”

    Blue Flag · Natural Medicines adverse-effect record, reported in cluster headache.

    2 sources cited
    1. 4. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
    2. 19. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.

    “Orally, blue flag can cause nausea and vomiting and the fresh blue flag root can irritate mucosa (4,19). The volatile oil constituent of blue flag irritates mucous membranes and can cause irritation of the throat (4).”

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

    2 sources cited
    1. 4. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
    2. 19. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Headache Additional detail

    Blue Flag

    “Orally, the volatile oil constituent of blue flag can cause headache (4).”

    Blue Flag · Natural Medicines adverse-effect record, reported in cluster headache.

    1 source cited
    1. 4. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

    Methotrexate

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

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Blue Flag 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

Blue Flag in Pregnancy & Breastfeeding

Lactation Likely Unsafe

When used orally; 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

From our Q&A

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

We hold 101 real supplement products containing Blue Flag, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Blue Flag. Even though Blue Flag 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 Blue Flag 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 Blue Flag
Steady interest

#1,172 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 Blue Flag reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Blue Flag 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 Blue Flag

What is Blue Flag?

  • Skin conditions like acne and eczema
  • Constipation and digestive complaints
  • Liver and gallbladder support (traditional)
  • Lymphatic and 'detox' tonic (traditional)
  • Thyroid and glandular swelling (traditional)

Blue Flag is a flowering plant whose root has been used in traditional and herbal medicine for skin and digestive complaints, but there is very little modern scientific evidence to support these uses. The fresh root can be toxic and irritating, so it should be used cautiously, if at all, and avoided in pregnancy and breastfeeding. Talk to a pharmacist or doctor before trying it.

Iris versicolor · Iridaceae · Dried rhizome (root) · Dried root, tincture, liquid extract, capsules, occasionally in topical preparations

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

Blue Flag: dosing

There is no well-established or standardized dose for Blue Flag, and reliable dosing information from quality clinical research is lacking. Traditional sources used small amounts of the dried root or tincture, but these are not validated by modern studies.If a product is used, follow the directions on the label and start low.

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

Read the full Blue Flag 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 & Blue Flag

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

1Major
77Moderate
0Minor
2,751No known interaction
1 Major 77 Moderate 2,751 No interaction
Major

1 interaction

Moderate

77 interactions

Showing 60 of 77 moderate interactions — see all 77 on the Blue Flag page.

No interaction 2,751 drugs checked — show the list

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

Showing the 60 most looked-up of 2,751 medications checked with no known interaction — see the full Blue Flag list.

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

Blue Flag References

The 3 references that drive our Blue Flag 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. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. 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. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.

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 Blue Flag and Methotrexate Together: Common Questions

Is it safe to take Blue Flag with Methotrexate?
We do not list a known interaction between Blue Flag 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 Blue Flag and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 3 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.
How was the Blue Flag and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Blue Flag has documented interactions with 3 drug classes — 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 Blue Flag interact with any other medications?
Yes. Blue Flag has 78 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 — Blue Flag 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

Blue Flag 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 3 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Blue Flag?

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.