Methylthioninium chloride (methylene blue) × Tramadol

IV methylene blue reversibly inhibits MAO-A. Tramadol inhibits serotonin and norepinephrine reuptake (plus weak opioid activity). Co-administration sharply raises monoamine levels.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.

Avoid the combination. Methylene blue is reserved for emergencies with tramadol withdrawn 24–72 hours in advance. For analgesia in patients who may require methylene blue, use paracetamol, NSAIDs, or a pure opioid (morphine, oxycodone).