Avoid Methylene Blue or Linezolid With Serotonergics

Physicians generally should avoid prescribing either methylene blue or linezolid (Zyvox,Pfizer) in combination with serotonergic agents such as paroxetine or duloxetine to avoid a potential drug interaction causing a dangerous condition called serotonin syndrome, the US Food and Drug Administration (FDA) announced today.
Linezolid is an antibacterial agent, and methylene blue is a dye used in diagnostic procedures and in the treatment of conditions ranging from methemoglobinemia to cyanide poisoning.


Through its Adverse Event Reporting System (AERS) database, the FDA has learned of serious central nervous system reactions when either drug has been given to patients taking other drugs that work through the serotonin system of the brain.

Both linezolid and methylene blue — each the subject of separate FDA press releases — inhibit the action of monoamine oxidase A, an enzyme that breaks down serotonin. Either drug, it is believed, can cause high levels of serotonin to build up in patients taking serotonergics, leading to the toxic condition called serotonin syndrome. Signs and symptoms include confusion, hyperactivity, and other mental changes; muscle twitching, excessive sweating, shivering, or shaking; diarrhea; trouble with coordination; and fever. In the case of linezolid, some deaths have been reported.

The FDA is advising clinicians that certain emergencies or life-threatening conditions warrant the administration of linezolid or methylene blue in patients taking serotonergic drugs. Linezolid may be needed for such patients to treat vancomycin-resistant Enterococcus faecium infections, or infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methemoglobinemia, cyanide poisoning, or ifosfamide-induced encephalopathy may require the emergency administration of methylene blue, according to the FDA.

In nonemergency situations, most serotonergic drugs must be discontinued at least 2 weeks before the start of linezolid or methylene blue therapy. Fluoxetine requires a 5-week lead time because of its longer half-life.

The FDA said that these and important recommendations as well as safety information about the potential interaction with serotonergic drugs will be added to the label of linezolid. The labels for serotonergic drugs will also be revised accordingly.

The agency is instructing patients taking either combination of drugs not to discontinue their serotonergic medication without first talking to their healthcare professional.

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