The FDA has issued new information about this safety issue, see the FDA Drug Safety Communication issued 10-20-2011.
[07-26-2011] The U.S. Food and Drug Administration (FDA) has received reports of serious central nervous system (CNS) reactions when the antibacterial drug linezolid (marketed as Zyvox) is given to patients taking psychiatric medications that work through the serotonin system of the brain (serotonergic psychiatric medications). A list of the serotonergic psychiatric medications that can interact with linezolid can be found here.
Used to treat infections, including pneumonia, infections of the skin, and infections caused by a resistant bacterium (Enterococcus faecium).
Is a reversible monoamine oxidase inhibitor (MAOI).
Although the exact mechanism of this drug interaction is unknown, linezolid inhibits the action of monoamine oxidase A—an enzyme responsible for breaking down serotonin in the brain. It is believed that when linezolid is given to patients taking serotonergic psychiatric medications, high levels of serotonin can build up in the brain, causing toxicity. This is referred to as Serotonin Syndrome—signs and symptoms include mental changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering or shaking, diarrhea, trouble with coordination, and/or fever.
You may need to temporarily stop taking your serotonergic psychiatric medication if it becomes necessary for you to take linezolid in certain situations. Your healthcare provider will tell you when to start linezolid after stopping your serotonergic psychiatric medication.
Do not stop taking your serotonergic psychiatric medicine without first talking to a healthcare professional.
Contact your healthcare professional immediately if you are taking a serotonergic psychiatric medication and develop any of the following symptoms: mental changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering or shaking, diarrhea, trouble with coordination, and/or fever.
Discuss any questions or concerns about linezolid or serotonergic psychiatric medications with your healthcare professional.
Report any serious side effects you experience to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.
Linezolid (Zyvox) can interact with serotonergic psychiatric medications and cause serious CNS toxicity.
In emergency situations requiring life-threatening or urgent treatment with linezolid (as described above), the availability of alternative interventions should be considered and the benefit of linezolid treatment should be weighed against the risk of serotonin toxicity. If linezolid 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 emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine [Prozac] was taken), or until 24 hours after the last dose of linezolid, whichever comes first.
In non-emergency situations when non-urgent treatment with linezolid is contemplated and planned, the serotonergic psychiatric medication should be stopped, to allow its activity in the brain to dissipate. Most serotonergic psychiatric drugs should be stopped at least 2 weeks in advance of linezolid treatment. Fluoxetine (Prozac), which has a longer half-life compared to similar drugs, should be stopped at least 5 weeks in advance.
Treatment with the serotonergic psychiatric medication may be resumed 24 hours after the last dose of linezolid.
Serotonergic psychiatric medications should not be started in a patient receiving linezolid. Wait until 24 hours after the last dose of linezolid before starting the antidepressant.
Report adverse events involving linezolid or serotonergic psychiatric medications to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.
Based on the available information provided in the AERS cases and literature, FDA has concluded that the concomitant administration of a serotonergic psychiatric medication with linezolid has the potential for a drug interaction causing serotonin syndrome. It appears this potential drug interaction can also occur following the discontinuation of serotonergic psychiatric medications with long half-lives. As a result, linezolid should generally not be given to patients taking serotonergic drugs unless the benefit is deemed to outweigh the risk.
Clark DB, Andrus MR, Byrd DC. Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature. Pharmacotherapy. 2006;26:269-76.