Methylthioninium chloride (methylene blue) × Mirtazapine

Methylene blue (methylthioninium chloride) inhibits monoamine oxidase (MAO). The US Food and Drug Administration (FDA) mirtazapine 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. Mirtazapine blocks presynaptic alpha-2 adrenergic receptors and enhances central noradrenergic and serotonergic transmission (mirtazapine labels). Together they can cause severe, sometimes fatal serotonin syndrome (methylene blue labels). No reports involved other routes of methylene blue, such as oral tablets or local tissue injection (FDA mirtazapine 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) mirtazapine label contraindicates mirtazapine 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 name mirtazapine among the drugs to avoid with methylene blue. If a patient on mirtazapine needs methylene blue, stop mirtazapine before it is given (FDA mirtazapine 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 mirtazapine and start supportive treatment (FDA labels of both drugs). Restart mirtazapine no earlier than 14 days after the last methylene blue dose (FDA mirtazapine label).