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Linezolid, Methylene Blue With Certain Psychiatric Drugs Can Cause Serious CNS Reactions

Cheryl A. Thompson

Health care professionals must bear in mind that linezolid and methylene blue inhibit monoamine oxidase A enough to cause serious central nervous system (CNS) reactions when given to patients already taking a serotonergic psychiatric medication, FDA announced Tuesday.

The agency said it has received reports of deaths from the simultaneous use of the antibacterial agent linezolid and a serotonergic psychiatric medication.

Lethargy, confusion, delirium, agitation, aggression, and coma have been reported in patients who received methylene blue while undergoing therapy with a serotonergic psychiatric medication, the agency said.

The serious CNS reactions, FDA said, are believed to result from toxic serotonin buildup in the brain.

Patients receiving therapy with a serotonergic psychiatric medication should not receive linezolid unless the infection is life-threatening or urgent treatment with the antibacterial is required, the agency said.

Also, patients receiving therapy with a serotonergic psychiatric medication should not receive methylene blue unless that drug is needed for the emergency treatment of methemoglobinemia, ifosfamide-induced encephalopathy, or cyanide poisoning.

In these situations, FDA advised clinicians to consider whether alternative interventions are available and whether the benefit of linezolid or methylene blue therapy outweighs the risk of serotonin toxicity.

If therapy with linezolid or methylene blue will proceed because of an emergency situation, then FDA said to immediately stop the serotonergic drug and closely monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of linezolid or methylene blue. Patients who had been receiving fluoxetine should be monitored for five weeks.

If the situation is not an emergency, then FDA said to stop therapy with the serotonergic drug at least two weeks—five weeks if the drug is fluoxetine—before linezolid or methylene blue treatment.

In all, FDA identified 29 serotonergic psychiatric medications on the U.S. market: 6 selective serotonin reuptake inhibitors, 3 serotonin–norepinephrine reuptake inhibitors, 8 tricyclic antidepressants, 4 monoamine oxidase inhibitors, amoxapine, bupropion, buspirone, maprotiline, mirtazapine, nefazodone, trazodone, and vilazodone.

Information about the potential drug interactions and drug-use recommendations are being added to the labeling for linezolid and the serotonergic psychiatric medications, FDA said.

Methylene blue, according to DailyMed, a federal database of drug labeling, is not an FDA-approved drug and does not have FDA-approved labeling.

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