The FDA has renewed its announcement to healthcare professionals and patients that the combined use of Xyrem (sodium oxybate) with alcohol or central nervous system (CNS) depressant drugs can markedly impair consciousness and may lead to severe breathing problems (respiratory depression). The use of alcohol with Xyrem is a new contraindication added to the Xyrem label, which already contraindicates its use with insomnia drugs. 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 be avoided.
Xyrem (sodium oxybate) is approved to reduce attacks of muscle weakness (cataplexy) and treat daytime sleepiness in patients with narcolepsy. Sodium oxybate, the active ingredient of Xyrem, is also known as gamma-hydroxybutyrate (GHB). GHB is a known drug of abuse that has been associated with central nervous system (CNS) adverse events, including death. Even at recommended doses, Xyrem can cause confusion, depression, and other neuropsychiatric events. Important CNS adverse events caused by abuse of GHB include seizures, respiratory depression, and profound decreases in level of consciousness, sometimes leading to coma and death.
Xyrem is available only through the Xyrem Success Program, which provides for restricted distribution of the drug through a central mail-order pharmacy.
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(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)
The FDA recently evaluated reports of patients who died while taking Xyrem along with alcohol or other CNS depressants. 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 (COPD). Given some of the circumstances noted in the deaths, however, the FDA determined that the recommendations in the Xyrem drug label should be changed to more strongly remind healthcare professionals and patients of the risks when using Xyrem with CNS depressant drugs or alcohol.
Specifically, using information from post-market adverse event reports submitted to the FDA's Adverse Event Reporting System (AERS) or to Xyrem’s manufacturer (Jazz Pharmaceuticals), the FDA evaluated reports of patients who died while taking Xyrem. The case descriptions were reviewed to determine whether Xyrem caused the deaths. Many of the reports of death were poorly documented or incomplete, making it impossible for the FDA to determine if patient deaths could be attributed to Xyrem.
A number of deaths occurred in patients who were reported to be concomitantly taking one or more medications that could depress the CNS. These drugs included neuroleptics, benzodiazepines, opioids, and others. In a few patients, many of these medications were being used concurrently. Other patients were reported to have ingested alcohol while taking Xyrem. A number of deaths occurred in patients who were prescribed Xyrem at doses that exceeded the recommended maximum dose or who underwent more rapid dose titration than recommended in the product label. Many of the deaths occurred in patients who were prescribed Xyrem 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 prescribed Xyrem who also had serious psychiatric disorders such as depression and substance abuse. A variety of concomitant illnesses were also present that may have predisposed some patients to the CNS and respiratory depressant effects of Xyrem.
See the FDA Safety Announcement