Drug & supplement interaction

Methylene Blue + Leflunomide

Leflunomide brand name: Arava.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between Methylene Blue and Leflunomide 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

Methylene Blue and Leflunomide

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 Leflunomide and Methylene Blue 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.

Methylene Blue safety at a glance

Methylene Blue overall Use caution It is a real drug with real risks; medical-grade forms need supervision and it should not be self-dosed casually.
Pregnancy Likely Unsafe PREGNANCY: Likely Unsafe when prescription methylene blue is used intra-amniotically. When provided during the second trimester, methylene blue has caused fetal... Read the full pregnancy detail
Breastfeeding Possibly Unsafe LACTATION: Possibly Unsafe when prescription methylene blue products are administered to patients who are lactating. Breast-feeding should be discontinued durin... 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 Leflunomide and Methylene Blue? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Leflunomide

Interactions in our licensed database are recorded against drug classes, not just single drug names. Leflunomide is filed under 3 classifications — cytochrome p450 2c9 (cyp2c9) inhibitors, hepatotoxic drugs, oral drugs. Methylene Blue has documented interactions with 2 drug classes — the most serious being anticholinergic drugs (moderate) and serotonergic drugs (moderate) — and none of Leflunomide’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

Methylene Blue Does Interact With Other Medications

Methylene Blue has 315 moderate known drug interactions in our database — Leflunomide isn’t one of them. If you take anything else, check it against the full list below.

Moderate 315 No known interaction 2,515 (incl. Leflunomide)
Taking anything else?

Check Another of Your Medications Against Methylene Blue

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

What to actually watch for

No Interaction Found — But Data Suggests Methylene Blue and Leflunomide 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. 5 of them are worth acting on rather than waiting out — marked below.

  • Yellowing of the skin or eyes Worth acting on Additional detail

    Methylene Blue

    “Orally, methylene blue has rarely resulted in mild-to-moderate acute increases in alanine transaminase, aspartate transaminase, or gamma-glutamyl transferase. Intravenously, methylene blue has resulted in elevated bilirubin and liver enzymes.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in hepatic.

    Leflunomide

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

  • A severe skin reaction Worth acting on Additional detail

    Methylene Blue

    “When used intravenously, blue skin, necrotic ulcers, papules, and phototoxicity have been reported. Extravasation has occurred following intravenous infusion of methylene blue. In one case, blistering and skin irritation occurred. Intraparenchymally, redness, broken blood vessels, and skin necrosis have been reported rarely.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in dermatologic.

    Leflunomide

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

  • Raised blood pressure Worth acting on Additional detail

    Methylene Blue

    “Orally: Hemolytic anemia, methemoglobinemia. Intravenous: Altered mental status, anaphylaxis, death, extravasation, hemolytic anemia, hypertension, methemoglobinemia, palpitations, phototoxicity, seizure-like symptoms, and tachycardia.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in general.

    “When used intravenously, hypertension, palpitations, and tachycardia have been reported.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in cardiovascular.

    Leflunomide

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

  • A severe allergic reaction Worth acting on Additional detail

    Methylene Blue

    “An anaphylactic-like reaction to methylene blue, requiring epinephrine, has been reported in an infant during surgery . However, skin-prick testing was negative. In a case report, a 44-year-old female developed a systemic allergic reaction with acute pulmonary edema following subcutaneous injection with methylene blue.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in immunologic.

    Leflunomide

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

  • An allergic reaction Worth acting on Additional detail

    Methylene Blue

    Recorded for Methylene Blue in the same Natural Medicines adverse-effect record shown under A severe allergic reaction above.

    Leflunomide

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

  • Bloating or gas / Dry mouth Additional detail

    Methylene Blue

    “Orally, gastrointestinal adverse effects are common, including abdominal pain, diarrhea, fecal discoloration, nausea, and vomiting. Blue feces, saliva, and vomitus have also occurred rarely when methylene blue is given for chromopertubation during laparoscopy. When used intravenously, the most common adverse events include diarrhea and nausea.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in gastrointestinal.

    Leflunomide

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

  • A stuffy or runny nose / Sore throat Additional detail

    Methylene Blue

    “When used intravenously, nasal congestion, runny nose, sneezing, and oropharyngeal pain have been reported.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in pulmonary/respiratory.

    Leflunomide

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

  • Blurred vision Additional detail

    Methylene Blue

    “When used intravenously, itchy and red eyes and blurred vision have been reported.”

    Methylene Blue · Natural Medicines adverse-effect record, reported in ocular/otic.

    Leflunomide

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

Showing the 10 most notable of 17 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for Methylene Blue but not commonly for Leflunomide: confusion, low magnesium, a fast or pounding heartbeat and low potassium.

Effects for Leflunomide come from the ADVERSE REACTIONS section of its FDA label; effects for Methylene Blue come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 104,033 voluntary FDA FAERS reports for Leflunomide 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

Methylene Blue in Pregnancy & Breastfeeding

Adults Likely Safe

Likely Safe when prescription methylene blue products are used intravenously and appropriately, short-term. Methylene blue is available as an FDA-approved prescription product. There is insufficient reliable information available about the safety of any form of supplemental or non-prescription methylene blue product.

Children Likely Safe

CHILDREN: Likely Safe when prescription methylene blue products are used intravenously and appropriately, short-term. Methylene blue is available as an FDA-approved prescription product. Cases of hemolytic anemia, hyperbilirubinemia, and acute renal failure have occurred rarely in neonates. CHILDREN: There is insufficient reliable information available about the safety of any form of supplemental or non-prescription methylene blue product.

Pregnancy Likely Unsafe

PREGNANCY: Likely Unsafe when prescription methylene blue is used intra-amniotically. When provided during the second trimester, methylene blue has caused fetal intestinal atresia and death. When used close to term, adverse effects have been reported in the newborn including hemolytic anemia, hyperbilirubinemia, methemoglobinemia, photosensitivity, and respiratory distress. Phototherapy and blood exchange transfusion have been required. PREGNANCY: There is insufficient reliable information available about the safety of methylene blue given by intrauterine injection during the first trimester. Inadvertent exposure in 4 case reports has not resulted in adverse effects. PREGNANCY: There is insufficient reliable information available about the safety of oral supplemental or non-prescription methylene blue products. However, fetal toxicity, including fetal loss, malformations, and reduced fetal weight, has been observed in animal studies at high doses.

Lactation Possibly Unsafe

LACTATION: Possibly Unsafe when prescription methylene blue products are administered to patients who are lactating. Breast-feeding should be discontinued during and for 8 days after treatment. LACTATION: There is insufficient reliable information available about the safety of oral supplemental or non-prescription methylene blue products.

Safety ratings from the Natural Medicines database. If you are pregnant or nursing, review any supplement with your OB or pharmacist first.

From our Q&A

Questions About Methylene Blue or Leflunomide

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Methylene Blue or Leflunomide, 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 Leflunomide

This page covers Methylene Blue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Leflunomide page lists 59 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Siberian Cocklebur (major), Wine (major) and Ashwagandha (moderate).

By severity: 4 major · 46 moderate · 9 minor.

From our pharmacist’s overview on the Leflunomide page

“Leflunomide (Arava) quiets rheumatoid arthritis by damping down the immune system, and its best-known danger is liver injury, so the 59 supplements and herbs on this page are worth slowing down for. Thirty-eight of them carry liver risks of their own, and of the four rated major, two are simply alcoholic drinks, while a third, Siberian…”

Reviewed by 2 · Jul 18, 2026

Open the Leflunomide interaction page

How much people look this up

Where Methylene Blue and Leflunomide 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 Methylene Blue
Top half

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

29 days ago today
Medication Leflunomide
Steady interest

#2,319 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 Methylene Blue reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Methylene Blue and Leflunomide records this page draws on were last updated July 16, 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 Methylene Blue

What is Methylene Blue?

Methylene Blue
  • Methemoglobinemia (a blood disorder)
  • Claimed energy or mental focus support
  • Anti-aging or longevity claims
  • Antimicrobial or antimalarial uses (historical)
  • Dye for medical and lab procedures

Methylene blue is a synthetic dye that is an FDA-approved prescription medicine for a rare blood disorder called methemoglobinemia, and it is also used as a diagnostic dye. Its popular use as a supplement for energy, brain health, or anti-aging is not well supported by solid human evidence, and it can cause serious side effects. Talk to a pharmacist or doctor before using it, and never take non-pharmaceutical or industrial-grade products.

Synthetic chemical compound (not derived from a plant) · Prescription injection, oral tablets, and compounded liquid or capsule supplements

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

Methylene Blue: dosing

There is no established safe supplement dose of methylene blue. In hospitals, medical doses are carefully calculated by weight and given by trained staff, which is very different from taking it on your own.Supplement products vary widely in strength and quality, and some sold online are not intended for people. If you are considering methylene blue, do not guess at a dose. They can review your health conditions and all your medicines to help you decide whether it is safe for you.

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

Read the full Methylene Blue monograph & all interactions
Medication

About Leflunomide

What Is Leflunomide Used For?

Brand name: Arava

Leflunomide tablets — sold under the brand name Arava and as generic leflunomide — are used to treat active rheumatoid arthritis (RA) in adults. Both Arava and generic leflunomide tablets are FDA-approved for this use.

Rheumatoid arthritis is an autoimmune condition in which the immune system attacks the joints, causing pain, swelling, and stiffness. Leflunomide helps calm that overactive immune response to reduce symptoms and slow joint damage.

Most-Reported Side Effects for Leflunomide

From FAERS, the FDA’s public side-effect reporting system (104,033 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 25,337 reports
Arthralgia 17,395 reports
Drug intolerance 15,935 reports
Joint swelling 15,925 reports
Fatigue 15,756 reports
See full Leflunomide drug information
Keep checking

Other Drugs & Methylene Blue

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

0Major
315Moderate
0Minor
2,514No known interaction
315 Moderate 2,514 No interaction
Moderate

315 interactions

Showing 60 of 315 moderate interactions — see all 315 on the Methylene Blue page.

No interaction 2,514 drugs checked — show the list

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

Showing the 60 most looked-up of 2,514 medications checked with no known interaction — see the full Methylene Blue list.

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

Methylene Blue References

The 60 references that drive our Methylene Blue 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. Chebolu E, Gnirke M, St Francis H, Soghoian S, Su MK. Extravasation with methylthioninium chloride. Clin Toxicol (Phila) 2024;62(11):776-778. PubMed
  2. Walter-Sack I, Rengelshausen J, Oberwittler H, et al. High absolute bioavailability of methylene blue given as an aqueous oral formulation. Eur J Clin Pharmacol. 2009;65(2):179-89. PubMed
  3. Akazawa M, Wu YH, Liu WM. Allergy-like reactions to methylene blue following laparoscopic chromopertubation: A systematic review of the literature. Eur J Obstet Gynecol Reprod Biol 2019;238:58-62. PubMed
  4. Aldeghaither S, Deschênes PJF, Samoukovic G. Anticholinergic Toxidrome as a Possible Explanation for Methylene Blue Toxicity. Am J Case Rep 2023;24:e941453. PubMed
  5. Liao YP, Hung DZ, Yang DY. Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. Vet Hum Toxicol 2002;44(1):19-21.
  6. Bilgin H, Ozcan B, Bilgin T. Methemoglobinemia induced by methylene blue pertubation during laparoscopy. Acta Anaesthesiol Scand 1998;42(5):594-5. PubMed
  7. Kirlangitis JJ, Middaugh RE, Zablocki A, Rodriquez F. False indication of arterial oxygen desaturation and methemoglobinemia following injection of methylene blue in urological surgery. Mil Med 1990;155(6):260-2. DOI
  8. Porat R, Gilbert S, Magilner D. Methylene blue-induced phototoxicity: an unrecognized complication. Pediatrics 1996;97(5):717-21. DOI
  9. Honoré PJ, Deianova N, Loret G, Hemelsoet D. An easily overlooked cause of toxic encephalopathy: methylene blue in a patient on an SSRI. Acta Neurol Belg 2018;118(1):121-122. PubMed
  10. McRobb CM, Holt DW. Methylene blue-induced methemoglobinemia during cardiopulmonary bypass? A case report and literature review. J Extra Corpor Technol 2008;40(3):206-14. DOI
  11. Donaldson CJ, Sequeira Campos M, El-Sayed M. Inadvertent foetal exposure to methylene blue in the first trimester. J Obstet Gynaecol 2020;40(4):573-574. PubMed
  12. Vanhinsbergh L, Uthaya S, Bain BJ. Methylene blue-induced Heinz body hemolytic anemia in a premature neonate. Am J Hematol 2018;93(5):716-717.
  13. Repici A, Di Stefano AF, Radicioni MM, Jas V, Moro L, Danese S. Methylene blue MMX tablets for chromoendoscopy. Safety tolerability and bioavailability in healthy volunteers. Contemp Clin Trials 2012;33(2):260-7. PubMed
  14. Lee DC, Valente JH. Methylene blue dye-induced knee effusion. Am J Emerg Med 1999;17(7):739-40. PubMed
  15. Albert M, Lessin MS, Gilchrist BF. Methylene blue: dangerous dye for neonates. J Pediatr Surg 2003;38(8):1244-5. 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 Methylene Blue and Leflunomide Together: Common Questions

Is it safe to take Methylene Blue with Leflunomide?
We do not list a known interaction between Methylene Blue and Leflunomide. 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 Methylene Blue and Leflunomide have any of the same side effects?
Yes — our sources link each of them separately to 10 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 Methylene Blue and Leflunomide combination checked?
Interactions in our licensed database are recorded against drug classes. Leflunomide is filed under 3 classifications, and Methylene Blue has documented interactions with 2 drug classes — none of Leflunomide'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 Methylene Blue interact with any other medications?
Yes. Methylene Blue has 315 documented drug interactions in our database — Leflunomide 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 Leflunomide interact with any supplements?
Yes. Leflunomide has documented interactions with 59 supplements in our database — Methylene Blue is not one of them. The Leflunomide 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

Methylene Blue monograph Uses, safety profile, and every drug interaction in one place Leflunomide drug information The full plain-English guide to this medication Leflunomide supplement interactions Every supplement checked against Leflunomide, 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 60 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Leflunomide and Methylene Blue?

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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.