Background

XYWAV is indicated for the treatment of idiopathic hypersomnia (IH) in adults.

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNING: CENTRAL NERVOUS SYSTEM
DEPRESSION and ABUSE AND MISUSE.

  • 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 idiopathic hypersomnia (IH) were receiving CNS stimulants.

  • Abuse and Misuse
    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.

Contraindications

XYWAV is contraindicated

  • in combination with sedative hypnotics or alcohol and
  • in patients with succinic semialdehyde dehydrogenase deficiency.

Warnings and Precautions

Central Nervous System Depression

The concurrent use of XYWAV with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If use of these CNS depressants in combination with XYWAV is required, dose reduction or discontinuation of one or more CNS depressants (including XYWAV) should be considered. In addition, if short-term use of an opioid (eg, post- or perioperative) is required, interruption of treatment with XYWAV should be considered.

After first initiating treatment and until certain that XYWAV does not affect them adversely (eg, impair judgment, thinking, or motor skills), 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 Ill controlled substance. The active moiety of XYWAV is oxybate, also known as gamma-hydroxybutyrate (GHB), a Schedule I controlled substance. Abuse 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. 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). Physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely.

XYWAV and XYREM REMS

  • Because of the risks of central nervous system depression and abuse and misuse, XYWAV is available only through a restricted distribution program called the XYWAV and XYREM REMS.

Notable requirements of the XYWAV and XYREM REMS include the following:

  • Healthcare Providers who prescribe XYWAV are specially certified
  • XYWAV will be dispensed only by the central pharmacy that is specially certified
  • XYWAV will be dispensed and shipped only to patients who are enrolled in the XYWAV and XYREM REMS with documentation of safe use

Further information is available at www.XYWAVXYREMREMS.com or 1-866-997-3688.

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 Study 2, the randomized-withdrawal clinical trial in adult patients with idiopathic hypersomnia (n=154), depression and depressed mood were reported in 1% and 3%, respectively, of patients treated with XYWAV. All patients continued XYWAV treatment.

Two suicides and two attempted suicides occurred in adult clinical trials with oxybate (same active moiety as XYWAV). One patient experienced suicidal ideation and two patients reported depression in a pediatric clinical trial with oxybate. These events occurred in patients with and without previous histories of depressive disorders. The emergence of depression in patients treated with XYWAV requires careful and immediate evaluation. Monitor patients for the emergence of increased depressive symptoms and/or suicidality while taking XYWAV.

Other Behavioral or Psychiatric Adverse Reactions

In Study 2, confusion and anxiety occurred in 3% and 16% of patients with idiopathic hypersomnia, respectively. One patient in Study 2 experienced visual hallucinations, which led to discontinuation of XYWAV.

Other neuropsychiatric reactions reported with oxybate (same active moiety as XYWAV) in adult or pediatric clinical trials and in the postmarketing setting include hallucinations, paranoia, psychosis, aggression, agitation, confusion, and anxiety. The emergence or increase in the occurrence of behavioral or psychiatric events in patients taking XYWAV should be carefully monitored.

Parasomnias

Parasomnias can occur in patients taking XYWAV.

In Study 2, parasomnias including sleepwalking were reported in 5% of adult patients with idiopathic hypersomnia treated with XYWAV.

Parasomnias, including sleepwalking, have been reported in postmarketing experience with sodium oxybate (same active moiety as XYWAV).

Episodes of sleepwalking should be fully evaluated and appropriate interventions considered.

Most Common Adverse Reactions

In Study 2, the most common adverse reactions occurring in ≥5% of XYWAV-treated patients were nausea, headache, anxiety, dizziness, insomnia, decreased appetite, hyperhidrosis, vomiting, dry mouth, diarrhea, fatigue, somnolence, parasomnia, and tremor.

INDICATION AND USAGE

XYWAV® (calcium, magnesium, potassium, and sodium oxybates) oral solution, 0.5 g/mL total salts (equivalent to 0.413 g/mL of oxybate) is indicated for the treatment of idiopathic hypersomnia (IH) in adults.

Please see full Prescribing Information, including BOXED Warning.

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US-XYW-2500217 Rev1025