Drug interactions
Methylene blue + Tramadol
Severity: Major
Methylene blue and Tramadol: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Methylene blue inhibits monoamine oxidase A, and tramadol inhibits reuptake of serotonin and norepinephrine. Together they can produce serotonin syndrome with agitation, hyperthermia, tremor, clonus and autonomic instability. Tramadol also carries a seizure risk that adds to the concern.
What this interaction means in plain words
Methylene blue and Tramadol can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Additive serotonergic activity through MAO-A inhibition by methylene blue and serotonin reuptake inhibition by tramadol.
What to do
Avoid the combination where an alternative analgesic or treatment is possible. If methylene blue is essential, stop tramadol and monitor for serotonin toxicity, and do not restart tramadol until at least 24 hours after the last methylene blue dose.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol Contraindicated
Frequently asked questions
Can I take Methylene blue with Tramadol?
MediHelp rates the interaction as major. Methylene blue and Tramadol can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Methylene blue inhibits monoamine oxidase A, and tramadol inhibits reuptake of serotonin and norepinephrine. Together they can produce serotonin syndrome with agitation, hyperthermia, tremor, clonus and autonomic instability. Tramadol also carries a seizure risk that adds to the concern.
How serious is the interaction between Methylene blue and Tramadol?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination where an alternative analgesic or treatment is possible. If methylene blue is essential, stop tramadol and monitor for serotonin toxicity, and do not restart tramadol until at least 24 hours after the last methylene blue dose.
What other medicines interact with Tramadol?
MediHelp also lists interactions of Tramadol with, for example, Isocarboxazid, Olanzapine / samidorphan, Phenelzine. The full list is on the Tramadol page.
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