Critical
Fluoxetine × Methylthioninium chloride (methylene blue)
Selective serotonin reuptake inhibitors×Antidotes (V03AB17). The drug has one FDA-approved indication – methaemoglobinaemia. Biohacker use is off-label.
Mechanism
IV methylene blue inhibits MAO-A. Fluoxetine and its active metabolite norfluoxetine raise synaptic serotonin. Norfluoxetine persists for up to 5 weeks – serotonin syndrome risk outlasts the dose by weeks.
Symptoms
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.
Management
Avoid the combination. Stop fluoxetine 5 weeks before planned methylene blue. In emergencies (methaemoglobinaemia), administer for life-threatening indications under ICU monitoring with cyproheptadine available.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.