Calcium oxybate, Magnesium oxybate, Potassium oxybate and Sodium oxybate

XYWAV is a central nervous system depressant indicated for the treatment of: • Cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. • Idiopathic Hypersomnia (IH) in adults.

XYWAV is a CNS depressant. The exact mechanism of action of XYWAV in the treatment of narcolepsy and idiopathic hypersomnia is unknown. XYWAV is a mixture of calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate (gamma-hydroxybutyrate). Gamma-hydroxybutyrate (GHB) is an endogenous compound and metabolite of the neurotransmitter GABA. It is hypothesized that the therapeutic effects of XYWAV are mediated through GABA B actions during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.

See Full Prescribing Information for complete dosing instructions ( 2.1 - 2.7 ). Dosage for Adult Patients with Narcolepsy • Initiate dosage at 4.5 g per night orally, divided into two doses. • Titrate to effect in increments of up to 1.5 g per night per week. • Recommended dosage range: 6 g to 9 g per night orally, divided into two doses. • Doses may be divided equally or unequally and the first dose taken at bedtime and the second dose taken 2.5 to 4 hours later. Dosage for Pediatric Patients with Narcolepsy (7 Years of Age and Older) • The recommended starting dosage, titration regimen, and maximum total nightly dosage are based on body weight. Dosage for Adult Patients with Idiopathic Hypersomnia • XYWAV can be administered as a twice or once nightly regimen in adults. • Twice nightly: Initiate dosage at 4.5 g or less per night orally, divided into two doses.

XYWAV is contraindicated for use in: • combination with sedative hypnotics. • combination with alcohol. • patients with succinic semialdehyde dehydrogenase deficiency. • In combination with sedative hypnotics or alcohol. • Succinic semialdehyde dehydrogenase deficiency

Boxed 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 narcolepsy and idiopathic hypersomnia were receiving central nervous system stimulants. • CNS depression: Use caution when considering the concurrent use of XYWAV with other CNS depressants. • Caution patients against hazardous activities requiring complete mental alertness or motor coordination within the first 6 hours of dosing or after first initiating treatment until certain that XYWAV does not affect them adversely. • Depression and suicidality: Monitor patients for emergent or increased depression and suicidality.

The following clinically significant adverse reactions appear in other sections of the labeling: • CNS depression • Abuse and Misuse • Respiratory Depression and Sleep-Disordered Breathing • Depression and Suicidality • Other Behavioral or Psychiatric Adverse Reactions • Parasomnias Most common adverse reactions in adults with narcolepsy or IH (≥5%) were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor. In a pediatric study with sodium oxybate (same active moiety as XYWAV), the most common adverse reactions (≥5%) were nausea, enuresis, vomiting, headache, weight decreased, decreased appetite, dizziness, and sleepwalking.

• Concomitant use with divalproex sodium: An initial reduction in XYWAV dose of at least 20% is recommended. Alcohol, Sedative Hypnotics, and CNS Depressants XYWAV is contraindicated for use in combination with alcohol or sedative hypnotics. Use of other CNS depressants may potentiate the CNS-depressant effects of XYWAV. Divalproex Sodium Concomitant use of sodium oxybate with divalproex sodium results in an increase in systemic exposure to GHB, which was shown to cause a greater impairment on some tests of attention and working memory in a clinical study. A similar increase in exposure is expected with concomitant use of XYWAV and divalproex sodium, therefore, an initial dose reduction of XYWAV is recommended when used concomitantly with divalproex sodium.

XYWAV should be stored between 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Storage Keep out of reach of children.