Methylene Blue and Maprotiline: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methylene Blue
Maprotiline
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of serotonin syndrome (labile blood pressure, hyperthermia, neuromuscular abnormalities, mental status changes, gastrointestinal symptoms)
Interaction Deep Dive
Concurrent use of maprotiline and methylene blue (an MAOI) is contraindicated1. Concurrent administration may result in potentially fatal serotonin syndrome 2. In settings where urgent treatment with methylene blue is not required, discontinue maprotiline at least 14 days prior to initiating treatment with methylene blue. If no alternative treatment is available and urgent methylene blue therapy is required in a patient on maprotiline therapy, and the potential benefits outweigh the risk of serotonin syndrome, maprotiline must be discontinued immediately 3. Use the lowest possible dose of methylene blue 2. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue has been administered, whichever comes first. Maprotiline may be resumed 24 hours after the last dose of methylene blue has been given 3.
Why it happens (mechanism)
Inhibition of MAO-mediated serotonin metabolism by methylene blue
Common questions
Can I take Methylene Blue and Maprotiline together?
An increased risk of serotonin syndrome (labile blood pressure, hyperthermia, neuromuscular abnormalities, mental status changes, gastrointestinal symptoms) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methylene Blue and Maprotiline interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Methylene Blue or Maprotiline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: maprotiline hcl oral tablets, maprotiline hcl oral tablets. Mylan Pharmaceuticals,Inc, Morgantown, WV, 2006.
- Product Information: PROVAYBLUE(TM) intravenous injection, methylene blue intravenous injection. American Regent (per FDA), Shirley, NY, 2016. DailyMed
- U.S. Food and Drug Administration: FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. U.S. Food and Drug Administration. Silver Spring, MD. 2011.
Keep reading about Methylene Blue
Keep reading about Maprotiline
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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