FDA Warning regarding Sodium Oxybate

The US Food and Drug Administration (FDA) has issued a warning against use of alcohol and central nervous system depressant drugs (CNS), such as benzodiazepines and opioids, with sodium oxybate ( Xyrem, Jazz Pharmaceuticals) because of the risk for impaired consciousness and respiratory depression leading to a respiratory arrest.

The drug, used to reduce episodes of cataplexy and treat daytime sleepiness in patients with narcolepsy, is already contraindicated for use with insomnia drugs. The new contraindications are reflected in labeling changes for the drug.

Sodium oxybate is also known as gamma-hydroxybutyrate (GHB). GHB is a known drug of abuse that has been associated with CNS adverse events, including death. Even at recommended doses, this drug can cause confusion, depression, and other neuropsychiatric events, the FDA notes.

FDA recently evaluated reports submitted to their Adverse Event Reporting System of patients who died while taking sodium oxybate along with alcohol or other CNS depressants, an FDA Safety Communication said.  "The cause of these deaths is not clear because the reports contained incomplete information and did not adequately address confounding factors, such as pre-existing sleep apnea and/or chronic obstructive lung disease," the FDA notes.

"Given some of the circumstances noted in the deaths, however, FDA determined that the recommendations in the Xyrem drug label should be strengthened to more strongly remind healthcare professionals and patients of the risks when using Xyrem with CNS depressant drugs or alcohol."

For example, many of the deaths occurred in patients who were reported to be concomitantly taking 1 or more medications that can depress the CNS, the FDA notes, including neuroleptics, benzodiazepines, and opioids, and in some, many such medications were being used together. Other patients were reported to have ingested alcohol while taking sodium oxybate.

Several deaths occurred in patients taking doses of the drug that exceeded the maximum recommended dose, or who had a more rapid dose titration than recommended in the label, the FDA adds. Many of the deaths occurred in patients who were prescribed this drug for unapproved uses, such as fibromyalgia, insomnia, or migraine. Some deaths were ascribed to drowning, suicide, or unknown causes.

Many of the deaths occurred in patients taking sodium oxybate who also had serious psychiatric disorders, such as depression and substance abuse, and a variety of concomitant illnesses were also present that may have predisposed some patients to the CNS and respiratory depressant effects of the drug, the FDA adds.

"The use of Xyrem with other CNS depressant drugs (drugs that affect the CNS and may lead to breathing problems) such as opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, general anesthetics, and muscle relaxants should generally be avoided," the agency concludes.

The Xyrem drug label is being revised as follows:

  • "The addition of the statement: 'Patients should not drink alcohol when using Xyrem.' ( Contraindications section)
  • The addition of a statement recommending that, when concomitant use of Xyrem with a central nervous system depressant is required, a reduction in dose or discontinuation of one or more central nervous system depressants (including Xyrem) should be considered; and a further recommendation that, if short-term opioid treatment is required, interruption of Xyrem treatment should be considered. ( Warnings and Precautions section)
  • The addition of a sentence stating that Xyrem may be dispensed only to patients enrolled in the Xyrem Success Program [which provides for restricted distribution of the drug through a central mail-order pharmacy] ( Indications and Usage section).
  • The addition of an updated summary of risks; a description of the components of the Xyrem Success Program; and details of the website and phone number where further information about Xyrem can be obtained ( Warnings and Precautions section)."

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

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