Xyrem (sodium oxybate) for narcolepsy
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What is Xyrem for narcolepsy?
Xyrem (sodium oxybate) is an approved oral therapy that’s used to treat excessive daytime sleepiness (EDS) or cataplexy in adults and children with narcolepsy.
In narcolepsy, the brain can’t properly regulate sleep-wake transitions. Nighttime sleep is disrupted, and aspects of sleep spill over into the waking hours, leading to uncontrollable urges to sleep during the day (EDS) and sudden attacks of lost muscle tone (cataplexy).
Sodium oxybate, the active ingredient in Xyrem, works as a central nervous system (CNS) depressant that slows brain activity and has a strong sedative effect. Its mechanisms in narcolepsy aren’t completely understood, but the medication is believed to modulate brain signaling chemicals to improve the quality of nighttime sleep. With better rest for the brain at night, symptoms like EDS and cataplexy during the day become less likely.
The brand-name medication is sold in the U.S. by Jazz Pharmaceuticals, with generic versions also available. The company also markets a lower-sodium alternative to Xyrem called Xywav in this area. In the European Union (EU), Xyrem is sold by UCB Pharma.
Therapy snapshot
| Brand name | Xyrem |
| Chemical name | Sodium oxybate |
| Usage | Used to treat excessive daytime sleepiness or cataplexy in adults and children with narcolepsy |
| Administration | Oral solution |
Who can take Xyrem?
In the U.S., Xyrem is approved for the treatment of EDS or cataplexy in adults and children with narcolepsy, ages 7 and older. In the EU and Canada, it is used only for adult patients with cataplexy.
Xyrem is contraindicated, or should not be used:
- in combination with sedative hypnotics — other CNS depressants with sedating and sleep-inducing properties — or alcohol
- in people with the very rare metabolic condition succinic semialdehyde dehydrogenase deficiency
Xyrem is only available through a restricted access program called Xywav and Xyrem Risk Evaluation and Mitigation Strategy (REMS) because it carries a boxed warning for very serious and potentially fatal risks:
- Xyrem is a CNS depressant that could lead to dangerously slow breathing (respiratory depression) or a state of reduced consciousness and alertness.
- It is a version of gamma-hydroxybutyric acid (GHB), a potent illicit sedative that has a high potential for abuse and can have life-threatening consequences.
How is Xyrem administered?
Xyrem comes as an oral liquid solution that should be taken twice a day at night. The recommended dosage varies by age:
- Adults: Starts at 4.5 grams total per night, which can be titrated at weekly intervals to a recommended total nightly dose of 6-9 grams.
- Children: Varies by body weight. There is insufficient information to provide dosing recommendations for children weighing less than 20 kg (about 44 pounds).
Each night, half of the total nightly dose should be taken at bedtime, at least two hours after eating. The other half should be taken two and a half to four hours after the initial dose. The Xyrem oral solution must be diluted in water using pharmacy-provided containers before use. Both doses should be prepared before bedtime.
Xyrem should always be taken while in bed, and patients should lie down immediately after dosing because they may fall asleep suddenly without feeling sleepy first.
People with liver impairment or those using certain other medications may require dose adjustments.
Xyrem in clinical trials
Xyrem’s approvals for people with narcolepsy were largely supported by five placebo-controlled clinical trials:
- One of the studies involved narcolepsy patients with moderate to severe cataplexy. Xyrem, at its recommended maintenance dose range, significantly reduced the rate of weekly cataplexy attacks compared with a placebo, while also easing daytime sleepiness.
- Another study involved people with narcolepsy and cataplexy, ages 16 and older, who were already using Xyrem. The data showed that people who switched to a placebo experienced a significant increase in weekly cataplexy attacks compared with people who stayed on the treatment.
- A third clinical trial involved adults with narcolepsy and cataplexy. The data showed that Xyrem at its recommended dose range was associated with significant reductions in patient-reported sleepiness relative to a placebo. Significantly more people on Xyrem than on the placebo were rated by their clinicians as very much or much improved in terms of narcolepsy symptoms.
- A Phase 3 trial (NCT00066170) involving adults with narcolepsy tested the effects of Xyrem alone and when combined with the approved therapy Provigil (modafinil). The results showed that Xyrem led to significant improvements in an objective measure of wakefulness relative to a placebo, with additional benefits when combined with Provigil.
- Another Phase 3 study (NCT02221869) established the benefits of Xyrem in children, ages 7-17, with narcolepsy and cataplexy. After a period on stable Xyrem, children who were switched to a placebo experienced a significant increase in weekly cataplexy attacks and worsening EDS relative to those who stayed on Xyrem.
Xyrem side effects
The most common side effects of Xyrem in adults include:
- nausea or vomiting
- dizziness
- sleepiness
- bed-wetting
- tremor
The most common side effects of Xyrem in children include:
- nausea or vomiting
- bed-wetting
- headache
- appetite or weight loss
- dizziness
- sleepwalking
According to the boxed warning, Xyrem’s actions as a CNS depressant can cause clinically significant respiratory depression and reduced consciousness, especially if used with alcohol or other CNS depressants. This can lead to life-threatening complications. If patients require other CNS depressants while using Xyrem, dose reductions or discontinuations of one or more medications may be required.
Activities that require complete mental alertness or motor coordination, such as driving, should always be avoided for at least six hours after taking Xyrem. Outside that window, patients should not engage in such activities until they are certain that the medication does not affect their ability to do so safely.
Because Xyrem is closely related to illicit GHB, it carries a risk of abuse or misuse. This can lead to serious complications, including seizures, life-threatening respiratory depression, decreased consciousness, coma, or death. Patients will be carefully monitored for signs of GHB misuse or abuse before initiating Xyrem and throughout treatment.
Patients will also be monitored throughout treatment for other potentially serious side effects, including:
- breathing problems during sleep, especially in people with existing risk factors
- depression and suicidal thoughts or behaviors
- other behavioral or psychiatric issues, such as confusion or anxiety
- abnormal movements during sleep, including sleepwalking
Xyrem also has a high sodium content, so its dosing should be carefully considered in people with existing cardiovascular and kidney problems.
Narcolepsy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
