Xywav (calcium, magnesium, potassium, and sodium oxybates) for narcolepsy
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What is Xywav for narcolepsy?
Xywav (calcium, magnesium, potassium, and sodium oxybates) is an oral therapy from Jazz Pharmaceuticals that’s approved to treat excessive daytime sleepiness (EDS) or cataplexy in adults and children with narcolepsy.
People with narcolepsy experience an uncontrollable need to sleep during the day (EDS) and sudden attacks of lost muscle tone (cataplexy) because their brain doesn’t properly regulate sleep-wake cycles.
Xywav contains various oxybate salts. Oxybate is a central nervous system (CNS) depressant that slows brain activity and has a sedative effect. Scientists don’t exactly know how it helps people with narcolepsy, but it’s believed to modulate brain signaling chemicals in ways that improve nighttime sleep. In turn, that prevents sleep-related symptoms like EDS and cataplexy from intruding into waking hours.
Other oxybate medications are approved in the U.S. for narcolepsy, including Xyrem, which is also marketed by Jazz. Xywav is the only one designed to be a low-sodium option, making it a safer alternative for people who require a low-sodium diet or have cardiovascular risk factors.
Xywav is also approved for treating adults with the sleep disorder idiopathic hypersomnia.
Therapy snapshot
| Brand name | Xywav |
| Chemical name | Calcium, magnesium, potassium, and sodium oxybates |
| Usage | Used to treat excessive daytime sleepiness or cataplexy in adults and children with narcolepsy |
| Administration | Oral solution |
Who with narcolepsy can take Xywav?
In the U.S., Xywav is approved for the treatment of EDS or cataplexy in adults and children with narcolepsy, ages 7 and older.
Xywav 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 metabolic condition succinic semialdehyde dehydrogenase deficiency
Like other oxybate medications, Xywav is only available through a restricted access program called Xywav and Xyrem Risk Evaluation and Mitigation Strategy (REMS) because it comes with a boxed warning for very serious and potentially fatal risks:
- Xywav is a CNS depressant that could lead to dangerously slow breathing (respiratory depression) or a state of reduced consciousness and alertness.
- The active ingredient in Xywav is a version of a potent illicit sedative called gamma-hydroxybutyric acid (GHB), the abuse of which can have life-threatening consequences.
How is Xywav administered in narcolepsy?
Xywav comes as an oral liquid solution to be taken twice daily at night. The recommended dosage varies by age:
- Adults: Starts at 4.5 grams total per night, increased 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).
The total nightly dose of Xywav should be split into two doses: the first should be taken at bedtime, at least two hours after eating, and the second should be taken two and a half to four hours later. The dose can be divided equally or unequally.
The Xywav oral solution must be diluted in water using pharmacy-provided containers before use. Both doses should be prepared before bedtime. Xywav should always be taken while in bed, and patients should lie down immediately after dosing.
People with liver impairment or those using certain other medications may require dose adjustments.
Xywav in narcolepsy clinical trials
Xywav’s approval for adults with narcolepsy was supported by a Phase 3 clinical trial (NCT03030599) involving 134 adults with narcolepsy and cataplexy. All participants started off on Xywav, and half later switched to a placebo. The results showed that:
- the median number of weekly cataplexy attacks was significantly increased in people who switched to the placebo compared with those who stayed on Xywav
- scores on a measure of patient-reported daytime sleepiness significantly worsened with the placebo compared with Xywav
Xywav’s pediatric approval was based on a Phase 3 clinical study (NCT02221869) of Xyrem that involved children with narcolepsy, ages 7-17. Similar to the data in adults, the study found that children who switched to a placebo showed significant increases in weekly cataplexy attacks and worsening EDS compared with those who stayed on Xywav.
Xywav side effects
The most common side effects of Xywav in adults include:
- nausea or vomiting
- headache
- dizziness
- anxiety
- insomnia
- decreased appetite
- excessive sweating
- diarrhea
- dry mouth
- sleepiness
- fatigue
- tremor
- abnormal movements during sleep (parasomnia), including sleepwalking
The most common side effects of Xywav in children include:
- nausea or vomiting
- bed-wetting
- headache
- appetite or weight loss
- dizziness
- sleepwalking
According to the boxed warning, because it is a CNS depressant, Xywav can cause respiratory depression and reduced consciousness, especially if used with alcohol or other CNS depressants. This can lead to life-threatening complications. If other CNS depressants are needed while using Xywav, dose reductions or discontinuations of one or more medications may be required.
Patients should avoid activities that require complete mental alertness or motor coordination, such as driving, for at least six hours after taking Xywav. Patients should not engage in such activities outside that window until they are certain that Xywav does not affect their ability to do so safely.
Illicit use of GHB carries a risk of abuse or misuse, which can lead to serious complications, including seizures, life-threatening respiratory depression, decreased consciousness, coma, or death. Because Xywav’s active ingredient is a form of GHB, patients using the medication will be carefully monitored for signs of abuse or misuse.
Other potentially serious side effects of Xywav include:
- 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
- parasomnia
Individuals will be carefully monitored for these complications while using Xywav.
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.
