Sodium oxybate (Xyrem) is a prescription medication used to treat two symptoms of narcolepsy: sudden muscle weakness and excessive daytime sleepiness
Sodium oxybate was approved for use by the FDA to treat symptoms of narcolepsy in 2002 with a strict risk evaluation and mitigation strategy (REMS) program mandated by the FDA. The US label for sodium oxybate also has a black box warning because it is a central nervous system depressant and may cause respiratory depression, seizures, coma, or death, especially if used in combination with other CNS depressants, such as alcohol and its use may cause dependence. In Canada and the European Union (EU) it was classified as a Schedule III and a Schedule IV controlled substance, respectively.
Between 1% and 10% of people experience nasal congestion, runny nose, or sore throat, loss of appetite, distorted sense of taste, cataplexy, weakness, nervousness or anxiety, depressed mood, nightmares or abnormal dreams, sleep paralysis, sleepwalking, or other sleep disturbances including insomnia, sleepiness or sedation, falls, vertigo, tremor, balance disorder, cognitive issues including disturbance in attention, confusion or disorientation, numbed sense of touch, tingling, blurred vision, heart palpitations, high blood pressure, shortness of breath, snoring, vomiting, diarrhea, stomach pain, excessive sweating, rashes, joint pain, muscle pain, back pain, muscle spasms, bedwetting, urinary incontinence, and swelling of the limbs.
Sodium oxybate is the sodium salt of γ-hydroxybutyric acid (GHB).
In the US, the cost (as of Q3 2015) of Xyrem is $5,468.09 per 180 mL bottle (500 mg/mL)(a 10 to 15-day supply). As of 2017 the cost of sodium oxybate in the UK was £540.00 to £1,080.00 for a thirty day supply, which at typical doses is £6,500 to £13,100 per year.\l "
https://dailymed.nlm...ef-411f0aa4f3ca
FDA drug insert
5.5 Depression and Suicidality
In adult clinical trials in patients with narcolepsy (n=781), there were two suicides and two attempted suicides in patients treated with Xyrem, including three patients with a previous history of depressive psychiatric disorder. Of the two suicides, one patient used Xyrem in conjunction with other drugs. Xyrem was not involved in the second suicide. Adverse reactions of depression were reported by 7% of 781 patients treated with Xyrem, with four patients (<1%) discontinuing because of depression. In most cases, no change in Xyrem treatment was required.
In a controlled adult trial, with patients randomized to fixed doses of 3 g, 6 g, or 9 g per night Xyrem or placebo, there was a single event of depression at the 3 g per night dose. In another adult controlled trial, with patients titrated from an initial 4.5 g per night starting dose, the incidences of depression were 1 (1.7%), 1 (1.5%), 2 (3.2%), and 2 (3.6%) for the placebo, 4.5 g, 6 g, and 9 g per night doses, respectively.
5.6 Other Behavioral or Psychiatric Adverse Reactions
During adult clinical trials in patients with narcolepsy, 3% of 781 patients treated with Xyrem experienced confusion, with incidence generally increasing with dose.
Less than 1% of patients discontinued the drug because of confusion. Confusion was reported at all recommended doses from 6 g to 9 g per night. In a controlled trial in adults where patients were randomized to fixed total daily doses of 3 g, 6 g, or 9 g per night or placebo, a dose-response relationship for confusion was demonstrated, with 17% of patients at 9 g per night experiencing confusion. In all cases in that controlled trial, the confusion resolved soon after termination of treatment. In Trial 3 where sodium oxybate was titrated from an initial 4.5 g per night dose, there was a single event of confusion in one patient at the 9 g per night dose. In the majority of cases in all adult clinical trials in patients with narcolepsy, confusion resolved either soon after termination of dosing or with continued treatment.
Anxiety occurred in 5.8% of the 874 patients receiving Xyrem in adult clinical trials in another population.
Other neuropsychiatric reactions reported in adult clinical trials in patients with narcolepsy and the post-marketing setting included hallucinations, paranoia, psychosis, aggression, and agitation.
In the pediatric clinical trial in patients with narcolepsy, neuropsychiatric reactions, including acute psychosis, confusion, and anxiety, were reported while taking Xyrem.
The emergence or increase in the occurrence of behavioral or psychiatric events in adult and pediatric patients taking Xyrem should be carefully monitored.
5.7 Parasomnias
Sleepwalking, defined as confused behavior occurring at night and at times associated with wandering, was reported in 6% of 781 patients with narcolepsy treated with Xyrem in adult controlled and long-term open-label studies, with <1% of patients discontinuing due to sleepwalking. Rates of sleepwalking were similar for patients taking placebo and patients taking Xyrem in controlled trials. It is unclear if some or all of the reported sleepwalking episodes correspond to true somnambulism, which is a parasomnia occurring during non-REM sleep, or to any other specific medical disorder. Five instances of significant injury or potential injury were associated with sleepwalking during a clinical trial of Xyrem in patients with narcolepsy.
Parasomnias, including sleepwalking, also have been reported in the pediatric clinical trial and in postmarketing experience with Xyrem. Therefore, episodes of sleepwalking should be fully evaluated and appropriate interventions considered.
5.3 Xyrem REMS Program
Xyrem is available only through a restricted distribution program called the Xyrem REMS Program because of the risks of central nervous system depression and abuse and misuse.
Notable requirements of the Xyrem REMS Program include the following:
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Healthcare Providers who prescribe Xyrem are specially certified
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Xyrem will be dispensed only by the central pharmacy that is specially certified
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Xyrem will be dispensed and shipped only to patients who are enrolled in the Xyrem REMS Program with documentation of safe use
Further information is available at www.XYREMREMS.com or 1-866-XYREM88® (1-866-997-3688).
9.3 Dependence
There have been case reports of withdrawal, ranging from mild to severe, following discontinuation of illicit use of GHB at frequent repeated doses (18 g to 250 g per day) in excess of the recommended dosage range. Signs and symptoms of GHB withdrawal following abrupt discontinuation included insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and, particularly in the case of severe withdrawal, visual hallucinations, agitation, and delirium. These symptoms generally abated in 3 to 14 days. In cases of severe withdrawal, hospitalization may be required. The discontinuation effects of Xyrem have not been systematically evaluated in controlled clinical trials. In the clinical trial experience with Xyrem in ith frenarcolepsy/cataplexy patients at recommended doses, two patients reported anxiety and one reported insomnia following abrupt discontinuation at the termination of the clinical trial; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time.
Note - This drug has been used as a date rape drug with frequent cases of respiratory failure and death.
