The FDA has issued an on the potential for serious central nervous system toxicity when patients taking serotonergic psychiatric drugs are treated with the antibacterial agent linezolid (Zyvox).
Cases of serotonin syndrome, which is characterized by mental changes, sweating or shivering, muscle twitching, and coordination problems, have been reported as an adverse interaction with linezolid for drugs of the selective serotonin reuptake inhibitor (SSRI) class as well as for serotonin-norepinephrine reuptake inhibitors (SNRI).
These classes of drugs include paroxetine (Paxil), fluvoxamine (Luvox), fluoxetine (Prozac, Symbyax) sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), vilazodone (Viibryd), venlafaxine (Effexor), desvenlafaxine (Pristiq), and duloxetine (Cymbalta).
While the precise mechanism by which linezolid interacts with these drugs has not been determined, it may result from inhibition of monoamine oxidase A. This enzyme is needed for the metabolism of serotonin in the brain, and its inhibition can lead to toxic buildup of this neurotransmitter.
At least one death has been reported.
"Healthcare professionals and patients may not realize that linezolid has monoamine oxidase inhibitor properties," the FDA stated.
Linezolid is used in the treatment of vancomycin-resistant Enterococcus faecium infections, pneumonia, and skin and soft-tissue infections -- including those caused by methicillin-resistant Staphylococcus aureus.
In an emergency situation when treatment with linezolid may be needed for a patient taking a serotonergic psychiatric drug, alternatives should be considered and the risks and benefits carefully weighed, the agency advised.
If linezolid must be used, the serotonergic drug must be stopped immediately, and the patient must be carefully monitored for two weeks for signs of serotonin syndrome -- except if the drug is fluoxetine, which has a long half-life, necessitating five weeks of monitoring.
If treatment with linezolid is considered in a nonemergency situation, the serotonergic agent should be stopped two weeks (five weeks for fluoxetine) before initiation of the antibacterial agent.
The agency also noted that other psychiatric medications have some serotonergic activity, though less than the SSRIs and SNRIs.
It is not known whether linezolid interacts with these other agents, which include tricyclic antidepressants and monoamine oxidase inhibitors.
The FDA notification also advised clinicians to educate their patients about the signs and symptoms of serotonin syndrome, and to report any such events to the agency's MedWatch program.