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Methylene blue interaction checker

Methylene blue acts like a strong MAOI. Combined with serotonergic drugs it can cause serotonin syndrome, a potentially fatal reaction the FDA flags in a boxed warning.

Reviewed 2026-08-21 · 9 sources

Select what you take

Tap every medication or supplement below that you use. Nothing is saved or sent.

Select the medications or supplements you take above, and this will show how each one interacts with Methylene Blue.

This checker flags documented and mechanistic interaction risks for education only. It is not medical advice, not a complete list of every interaction, and not a substitute for your prescriber or pharmacist. Never start, stop, or combine medications based on this tool alone.

Why methylene blue interacts like an MAOI

Methylene blue is a potent, reversible inhibitor of monoamine oxidase A (MAO-A), the enzyme that clears serotonin from the synapse, with an inhibition constant around 27 nM. When MAO-A is blocked and another drug is also raising serotonin, serotonin can build to dangerous levels and trigger serotonin syndrome. That is why a compound sold as a dye behaves like a strong MAOI. The effect is dose-related: even 0.75 to 1 mg/kg intravenously can reach levels that inhibit MAO-A.

What serotonin syndrome is

A potentially life-threatening reaction caused by too much serotonin activity in the nervous system. It is a predictable drug effect, not an allergy, and it can come on within hours of the combination.

Symptoms to watch for

  • -Agitation, confusion, or restlessness
  • -Fast heart rate and high blood pressure
  • -Fever, heavy sweating, shivering
  • -Muscle twitching, tremor, or rigidity
  • -Overactive reflexes and clonus
  • -Nausea, diarrhea

Severe cases cause dangerously high fever, seizures, and organ failure and are a medical emergency. If these symptoms appear after combining serotonergic drugs, seek emergency care immediately - do not wait it out.

Timing and washout

The FDA label tells patients not to take serotonergic drugs within 72 hours after their last methylene blue dose. There is no single verified answer for how long to stop an antidepressant before methylene blue - it depends heavily on the drug (fluoxetine, for example, can linger for weeks). That timing is a decision for your prescriber, not a fixed number.

The methylene blue reference->Check your methylene blue grade->

Sources

  1. [1]PROVAYBLUE (methylene blue) injection - FDA-approved label (DailyMed)labelThe boxed warning on serotonergic syndrome, the named drug classes and specific drugs, and the 72-hour post-treatment timing guidance.
  2. [2]Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of MAO A. Br J Pharmacol. 2007studyMethylene blue is a potent reversible MAO-A inhibitor (Ki about 27 nM), the mechanism behind the serotonin-toxicity risk.
  3. [3]Gillman PK. CNS toxicity involving methylene blue... serotonin toxicity. J Psychopharmacol. 2011reviewThe dose-risk relationship: 0.75 mg/kg IV produces MAO-A-inhibiting levels, and severe toxicity is reported at doses as low as 1 mg/kg.
  4. [4]Boyer EW, Shannon M. The Serotonin Syndrome. N Engl J Med. 2005 PMID 15784664reviewThe classic clinical description of serotonin syndrome - mechanism, symptom spectrum, and management - and the strong association of MAO-A inhibitors with severe cases.
  5. [5]Ng BKW, Cameron AJD. The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics. 2010 PMID 20484716studyIn a 26-patient case series, 24 were on a serotonin reuptake inhibitor and one on clomipramine when methylene blue precipitated toxicity.
  6. [6]McMillan et al. Serotonergic Drug Use in Patients Exposed to Perioperative Methylene Blue. Cureus. 2025 (PMC12017462)studyConfirms the FDA black-box warning and that MAO-A inhibition is reached at IV doses as low as 0.75 mg/kg.
  7. [7]Dextromethorphan (StatPearls, NCBI Bookshelf NBK538216)reviewExplicitly names methylene blue among the MAOIs that must not be combined with dextromethorphan due to life-threatening serotonin syndrome risk.
  8. [8]Serotonin Syndrome (StatPearls, NCBI Bookshelf NBK482377)reviewSymptom list, severity spectrum, medical-emergency status, and that MAOI-involved cases tend to be the most severe.
  9. [9]Bupropion (StatPearls, NCBI Bookshelf NBK470212)reviewBupropion inhibits dopamine and norepinephrine transporters with minimal effect on serotonin, the basis for its lower serotonin-syndrome risk.