FDA Warns About Nervous System Reactions from Zyvox, Methylene Blue

Federal drug regulators are warning that there is a risk of serious central nervous system reactions when the drugs Zyvox and methylene blue are used with some antidepressants, including Paxil, Zoloft, Prozac and Cymbalta, among many others. 

The FDA issued a drug safety communications for methylene blue and Zyvox on Tuesday, indicating that the agency analyzed adverse event reports that included reports of central nervous system (CNS) toxicity and some deaths. The reactions were due to drug interactions between the two drugs and psychiatric medications that affect the serotonin system of the brain, according to the FDA warning.

Methylene blue and Zyvox are both reversible monoamine oxidase inhibitors (MAOI). Methylene blue is used to treat cyanide poisoning, methemoglobinemia, vasoplegic syndrome and ifosfamide-induced encephalopathy. It is also used as a dye in therapeutic and diagnostic applications. Zyvox (linezolid) is used to treat infections, including pneumonia, skin infections and methicillin-resistant Staphylococcus aureus (MRSA).

The FDA warning includes a full list of serotonergic psychiatric medications that could react with the drugs. The list includes selective serotonin reuptake inhibitors (SSRIs), which are the most common psychiatric drugs on the market, as well as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs) and other MAOIs and psychiatric drugs. The list includes some of the most prescribed drugs in the world, such as Paxil, Prozac, Zoloft, Celexa, Lexapro, Effexor, Cymbalta, Wellbutrin and Zyban.

Why the interaction between the drugs causes CNS toxicity is unknown, but the FDA states that some experts believe that the Zyvox and methylene blue cause high levels of serotonin to build up in the brain when used with the serotonergic drugs, resulting in toxicity. This is known as serotonin syndrome and can cause confusion, hyperactivity, memory loss, muscle twitching, excessive sweating, shivering and shaking, diarrhea, fever and trouble with coordination.

The agency is recommending that patients prescribed methylene blue and Zyvox should be taken off of any of the listed antidepressants two weeks prior. However, in some cases the drugs are given as an emergency treatment. In those instances, doctors should attempt to find an alternative method of treatment, the FDA recommended.

The antidepressants can be resumed 24 hours after the last dose of methylene blue and Zyvox, the FDA stated.