Overview
11 DESCRIPTION XYWAV oral solution contains oxybate, a CNS depressant. The chemical name of oxybate is gamma-hydroxybutyrate (GHB). XYWAV contains a mixture of calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate equivalent to 0.5 g/mL, which corresponds to 0.413 g/mL oxybate. Each mL of XYWAV contains: 0.234 g calcium oxybate, Ca(C 4 H 7 O 3 ) 2 ; 0.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.3 Pharmacokinetics Pharmacokinetics of GHB are nonlinear and are similar following single or repeat dosing.
Indications
- 1 INDICATIONS AND USAGE 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 ( 1.1 ). • Idiopathic Hypersomnia (IH) in adults ( 1.2 ). 1.1 Narcolepsy XYWAV is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. 1.2 Idiopathic Hypersomnia XYWAV is indicated for the treatment of idiopathic hypersomnia (IH) in adults.
Common Doses
- 4.5 g
- 1.5 g
- 6 g
- 9 g
Dosage
2 DOSAGE AND ADMINISTRATION 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 ( 2.1 ). • Titrate to effect in increments of up to 1.5 g per night per week ( 2.1 ). • Recommended dosage range: 6 g to 9 g per night orally, divided into two doses ( 2.1 ). • 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 ( 2.1 ).
Black Box Warning
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 [see Warnings and Precautions ( 5.1 , 5.4 )]. Many patients who received XYWAV during clinical trials in narcolepsy and idiopathic hypersomnia were receiving central nervous system stimulants [see Clinical Studies ( 14.1 , 14.2 , 14.3 )]. • Abuse and Misuse The active moiety of XYWAV is oxybate or gamma-hydroxybutyrate (GHB).
Contraindications
- 4 CONTRAINDICATIONS XYWAV is contraindicated for use in: • combination with sedative hypnotics [see Warnings and Precautions ( 5.1 )] . • combination with alcohol [see Warnings and Precautions ( 5.1 , 5.2 )] . • patients with succinic semialdehyde dehydrogenase deficiency [see Clinical Pharmacology ( 12.3 )] . • In combination with sedative hypnotics or alcohol ( 4 ) • Succinic semialdehyde dehydrogenase deficiency ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions appear in other sections of the labeling: • CNS depression [see Warnings and Precautions ( 5.1 )] • Abuse and Misuse [see Warnings and Precautions ( 5.2 )] • Respiratory Depression and Sleep-Disordered Breathing [see Warnings and Precautions ( 5.4 )] • Depression and Suicidality [see Warnings and Precautions ( 5.5 )] • Other Behavioral or Psychiatric Adverse Reactions [see Warnings and Precautions ( 5.6 )] • Parasomnias [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS • Concomitant use with divalproex sodium: An initial reduction in XYWAV dose of at least 20% is recommended ( 2.7 , 7.2 ). 7.1 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 [see Warnings and Precautions ( 5.1 )] . 7.2 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...