Drug interactions between Adapin and methylene blue

doxepin ↔ methylene blue

Applies to:Adapin (doxepin) and methylene blue

CONTRAINDICATED: Concomitant use of methylene blue injectable with serotonin reuptake inhibitors or other serotonergic agents may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Current research suggests that methylene blue has structural properties similar to monoamine oxidase inhibitors, which are known to precipitate serotonin toxicity when coadministered with serotoninergic agents, especially selective serotonin reuptake inhibitors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Serotonin syndrome has been reported when methylene blue was administered intravenously at dosages as low as 1 mg/kg to patients exposed to drugs that interfere with serotonin reuptake. Several cases required admission to the intensive care unit.

MANAGEMENT: Serotonergic agents should not be used in patients receiving methylene blue injectable. If possible, patients treated with serotonergic agents should discontinue these medications for at least 4 to 5 half-lives prior to administration of methylene blue injectable. Most serotonergic psychiatric drugs should be stopped at least 2 weeks in advance of methylene blue treatment, while fluoxetine should be stopped at least 5 weeks in advance due to its prolonged half-life. Treatment with serotonergic medications may be resumed 24 hours after the last dose of methylene blue. In emergency situations requiring urgent treatment with methylene blue (e.g., methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning), the availability of alternative interventions should be considered and the benefit of methylene blue treatment should be weighed against the risk of serotonin toxicity. If methylene blue is required in a patient receiving a serotonergic drug, the serotonergic drug must be immediately stopped, and the patient closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine was taken) or until 24 hours after the last dose of methylene blue, whichever comes first. Patients and/or their caregivers should be advised to seek medical attention if potential symptoms of serotonin syndrome develop.