The FDA is alerting physicians and patients that the monoamine oxidase inhibitors, or MAOIs, linezolid and methylene blue have been linked to reports of serious central nervous system reactions in patients taking serotonergic psychiatric medications.
In safety communications issued July 26, the agency said linezolid(www.fda.gov), an antibacterial drug marketed as Zyvox, and methylene blue(www.fda.gov) both inhibit the action of monoamine oxidase A, an enzyme responsible for breaking down serotonin in the brain. Giving either drug to patients taking serotonergic psychiatric medications can lead to serotonin syndrome. Signs and symptoms of serotonin syndrome, which can be life-threatening, include confusion, hyperactivity, memory problems, muscle twitching, excessive sweating, shivering or shaking, diarrhea, trouble with coordination, and/or fever.
According to the FDA, more than two dozen medications can interact with linezolid and methylene blue, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricylic antidepressants, other MAOIs and a number of other psychiatric medications. Both safety documents contain a complete list of these agents.
- The FDA is alerting physicians and patients that concomitant administration of serotonergic psychiatric medications and either linezolid or methylene blue can lead to serotonin syndrome.
- The agency said serotonergic psychiatric medications should not be prescribed to patients taking linezolid or methylene blue except in certain life-threatening or urgent situations.
Serotonin syndrome associated with concomitant administration of linezolid and a serotonergic psychiatric medication has resulted in patient deaths, said the agency, and linezolid generally should not be given to patients taking these drugs except in the following urgent or life-threatening circumstances:
- to treat vancomycin-resistant Enterococcus faecium infections; and
- to treat infections such as nosocomial pneumonia and complicated skin and skin structure infections, including cases caused by methicillin-resistant Staphylococcus aureus.
Similarly, the FDA said methylene blue -- which is commonly used as a dye in diagnostic procedures and also is used to treat a number of medical conditions -- generally should not be given to patients taking serotonergic drugs except in the following urgent or life-threatening situations:
- to treat methemoglobinemia;
- to treat ifosfamide-induced encephalopathy; and
- to treat cyanide poisoning.
The agency said that in such emergency situations, alternative interventions should be considered and the benefit of linezolid or methylene blue treatment should be weighed against the risk of toxicity. If linezolid or methylene blue must be administered to a patient receiving a serotonergic drug, the serotonergic drug must be immediately stopped and the patient should be closely monitored for symptoms of toxicity for two weeks or until 24 hours after the patient's final dose of the MAOI, whichever comes first. Monitoring should be expanded to five weeks if fluoxetine, which is marketed as Prozac, is the serotonergic drug in question, or until 24 hours after the patient's final dose of the MAOI.
The FDA issued the following information for physicians contemplating the use of linezolid or methylene blue in nonurgent situations for patients taking serotonergic psychiatric medications:
- the serotonergic psychiatric medication should be stopped at least two weeks in advance, and at least five weeks in advance with fluoxetine, to allow the antidepressant's activity in the brain to dissipate;
- treatment with the serotonergic psychiatric medication may be resumed 24 hours after the last dose of the MAOI;
- serotonergic psychiatric medications should not be started in a patient receiving linezolidor or methylene blue. Wait until 24 hours after the last dose of the MAOI before starting the antidepressant; and
- educate patients to recognize the symptoms of toxicity and advise them to contact a health care professional immediately if they experience any such symptoms while taking serotonergic psychiatric medications, linezolid or methylene blue.
Physicians are encouraged to report adverse events involving linezolid, methylene blue or serotonergic psychiatric medications to the FDA's MedWatch program(www.accessdata.fda.gov).