Methylthioninium chloride (methylene blue) × Sertraline

Methylene blue (methylthioninium chloride) inhibits monoamine oxidase (MAO). The US Food and Drug Administration (FDA) sertraline label classes intravenous methylene blue as an MAO inhibitor, and the FDA methylene blue label cites literature describing it as a potent reversible inhibitor of this enzyme. Sertraline blocks serotonin reuptake. Together they can cause severe, sometimes fatal serotonin syndrome (methylene blue labels). The Spanish sertraline SmPC reports serious reactions, including deaths, also when sertraline was started soon after stopping an MAO inhibitor such as methylene blue, or an MAO inhibitor was started right after stopping sertraline. No reports involved other routes of methylene blue, such as oral tablets or local tissue injection (FDA sertraline label).

Serotonin syndrome. Mental status changes: agitation, hallucinations, delirium, coma. Autonomic signs: tachycardia, labile blood pressure, dizziness, sweating, flushing, fever. Neuromuscular signs: tremor, rigidity, myoclonus, hyperreflexia, incoordination. Seizures, nausea, vomiting and diarrhoea may occur. Some reported cases were fatal (FDA methylene blue label).

The combination is contraindicated: the US Food and Drug Administration (FDA) sertraline label contraindicates sertraline in patients taking MAO inhibitors, including intravenous methylene blue, or within 14 days of stopping them. The methylene blue labels approved by the European Medicines Agency (EMA) and the FDA say to avoid it in patients taking selective serotonin reuptake inhibitors. If a patient on sertraline needs methylene blue, stop sertraline before it is given (FDA sertraline label). When methylene blue cannot be avoided, give the lowest possible dose and observe the patient for nervous system effects for 4 hours (methylene blue labels). Monitor the ECG and blood pressure during and after the infusion (EMA methylene blue SmPC). If signs of serotonin syndrome appear, stop methylene blue and sertraline and start supportive treatment (FDA labels of both drugs). Restart sertraline no earlier than 14 days after the last methylene blue dose (FDA sertraline label).