XYWAV is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.
- Central Nervous System Depression
XYWAV is a CNS depressant. Clinically significant respiratory depression and obtundation may occur in patients treated with XYWAV at recommended doses. Many patients who received XYWAV during clinical trials in narcolepsy were receiving CNS stimulants.
The active moiety of XYWAV is oxybate or gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.
Because of the risks of CNS depression and abuse and misuse, XYWAV is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Xywav and Xyrem REMS.
- CNS Depression: Use caution when considering the concurrent use with other CNS depressants. If concurrent use is required, consider dose reduction or discontinuation of one or more CNS depressants (including XYWAV). Consider interrupting XYWAV treatment if short-term opioid use is required. After first initiating treatment and until certain that XYWAV does not affect them adversely, caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes. Also caution patients against these hazardous activities for at least 6 hours after taking XYWAV. Patients should be queried about CNS depression-related events upon initiation of XYWAV therapy and periodically thereafter.
- Abuse and Misuse: XYWAV is a Schedule III controlled substance. The rapid onset of sedation, coupled with the amnestic features of GHB particularly when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user (eg, assault victim).
- Respiratory Depression and Sleep-Disordered Breathing: XYWAV may impair respiratory drive, especially in patients with compromised respiratory function. In overdoses of oxybate and with illicit use of GHB, life-threatening respiratory depression has been reported. Increased apnea and reduced oxygenation may occur with XYWAV administration in adult and pediatric patients. A significant increase in the number of central apneas and clinically significant oxygen desaturation may occur in patients with obstructive sleep apnea treated with XYWAV. Prescribers should be aware that sleep-related breathing disorders tend to be more prevalent in obese patients, in men, in postmenopausal women not on hormone replacement therapy, and among patients with narcolepsy.
- Depression and Suicidality: In a randomized-withdrawal clinical trial in adult patients with narcolepsy (n=201), depression and depressed mood were reported in patients treated with XYWAV. In most cases, no change in XYWAV treatment was required. In clinical trials of Xyrem (same active moiety as XYWAV) in adult patients with narcolepsy (n=781), depression was reported by 7% of Xyrem-treated patients, with four patients (<1%) discontinuing because of depression. In the pediatric clinical trial with Xyrem in patients with narcolepsy (n=104), one patient experienced suicidal ideation while taking XYREM. Monitor patients for the emergence of increased depressive symptoms and/or suicidality while taking XYWAV, which require careful and immediate evaluation.
- Other Behavioral or Psychiatric Adverse Reactions: Monitor patients for impaired motor/cognitive function or the emergence of or increase in anxiety and/or confusion. The emergence or increase in the occurrence of behavioral or psychiatric events in patients taking XYWAV should be carefully monitored.
- Parasomnias: In a randomized-withdrawal clinical trial, parasomnias, including sleepwalking were reported in adult patients treated with XYWAV. Parasomnias, including sleepwalking, also have been reported in a pediatric clinical trial with sodium oxybate (same active moiety as XYWAV) and in postmarketing experience with sodium oxybate. Episodes of sleepwalking should be fully evaluated and appropriate interventions considered.
In the adult clinical trial, in patients with narcolepsy, the most common adverse reactions (incidence ≥5% of XYWAV-treated patients) were headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis, anxiety, and vomiting.
In the pediatric clinical trial with Xyrem (same active moiety as XYWAV) in patients 7 years of age and older with narcolepsy, the most common adverse reactions (≥5%) were enuresis (18%), nausea (17%), headache (16%), vomiting (16%), weight decreased (12%), decreased appetite (8%), and dizziness (6%). The safety profile in pediatric patients with XYWAV is expected to be similar to that of adult patients treated with XYWAV and to that of pediatric patients treated with Xyrem.
Please see Important Safety Information and full Prescribing Information, including BOXED Warning.
- XYWAVTM (calcium, magnesium, potassium, and sodium oxybates) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals.
- Thorpy MJ. Recently approved and upcoming treatments for narcolepsy. CNS Drugs. 2020;34(1):9-27.
- Data on file. JZP258-2020-008, Jazz Pharmaceuticals.