The antibacterial drug linezolid and methylene blue can interact with serotoninergic psychiatric drugs, resulting in serious central nervous system reactions, the Food and Drug Administration announced July 26 in two separate but similarly worded safety advisories.
Cases of serotonin syndrome associated with concomitant administration of linezolid and serotoninergic psychiatric medications, including some deaths, have been reported to the FDA’s adverse event reporting system (AERS), according to one of the statements. More cases were identified in a literature search, including at least one fatal case (Pharmacotherapy 2006;26:269-76).
Serious CNS reactions have also been reported to AERS in patients treated with methylene blue and serotonergic psychiatric medications, and more cases have also been reported in the literature, according to the second advisory, which does not mention any reports of fatal cases. These events have included reports of lethargy, confusion, delirium, and coma – often with neurologic symptoms, such as myoclonus, expressive aphasia, seizures, or autonomic symptoms.
The exact mechanism of action behind these interactions is unknown, the FDA statement says, but adds that both agents are known reversible monoamine oxidase inhibitors and when either is administered along with a serotonergic medication, high levels of serotonin can build up in the brain resulting in serotonin syndrome, which is characterized by symptoms that include mental changes.
The statements advise that linezolid or methylene blue should "generally not be given" to patients on serotonergic drugs. However, the FDA adds that "there are some conditions that may be life threatening or require urgent treatment" with either agent.
In the case of linezolid, those situations include when linezolid is needed to treat vancomycin-resistant Enterococcus faecium (VRE) or other types of infections such as nosocomial pneumonia or complicated skin and skin structure infections, including those cases caused by methicillin-resistant Staphylococcus aureus. For methylene blue, those cases include methemoglobinemia, cyanide poisoning, or ifosfamide-induced encephalopathy.
The advisories include a complete list of psychiatric drugs with serotonergic activity, including selective serotonin reuptake inhibitors and tricyclic antidepressants.
Serious adverse reactions resulting from concomitant use of linezolid or methylene blue and serotonergic drugs should be reported to the FDA’s MedWatch program or at 800-332-1088.