Usual Adult Dose for Narcolepsy

Initial dose: 4.5 g orally per day, divided and given as 2 equal doses of up to 2.25 g/dose
Maintenance dose: The dose may be increased by 1.5 g (OR 0.75 g/dose) orally per night in weekly intervals up to 6 to 9 g/day.
Maximum dose: 9 g/day

Comments:

• Both doses should be diluted at the same time at night.
• The first dose should be taken at bedtime and the other dose should be taken between 2.5 to 4 hours after; some may need to set an alarm to awaken to take the second dose.
• Patients should remain in bed after taking each dose.
• If the second dose is missed, patients should skip the dose and should not take this drug until the next night.
• Dosing may be gradually titrated, and doses should be determined by efficacy and tolerability.

Use: Treatment of cataplexy (excessive daytime sleepiness) in patients with narcolepsy

Usual Adult Dose for Idiopathic Hypersomnia

2 times a night regimen:

• Initial dose: 4.5 g orally per day, divided and given as 2 equal doses
• The dose may be increased by 1.5 g (OR 0.75 g/dose) orally per night in weekly intervals
• Maintenance dose: 6 to 9 g/day
• Maximum dose: 9 g/day

Once a night regimen:

• Initial dose: 3 g orally per day, divided and given as 2 equal doses
• The dose may be increased by 1.5 g (OR 0.75 g/dose) orally per night in weekly intervals
• Maintenance dose: 3 to 6 g/day
• Maximum dose: 6 g/day

Comments:

• This drug may be given in divided doses or as a single dose.
• Dosing may be gradually titrated, and doses should be determined by efficacy and tolerability.
• Patients may respond better with the first dose given at bedtime and the second dose given between 2.5 to 4 hours later.

Use: Treatment of idiopathic hypersomnia

Usual Pediatric Dose for Narcolepsy

7 years and older:
Less than 20 kg: Specific dosing recommendations are not available.

20 to less than 30 kg:

• Initial dose: Up to 2 g orally per day, divided and given as 2 equal doses of up to 1 g/dose
• Maintenance dose: The dose may be increased by 1 g (OR 0.5 g/dose) orally per night at 1 to 2-week intervals up to 6 g/day.
• Maximum dose: 6 g/day

30 to less than 45 kg:

• Initial dose: Up to 3 g orally per day, divided and given as 2 equal doses of up to 1.5 g/dose
• Maintenance dose: The dose may be increased by 1 g (OR 0.5 g/dose) orally per night at 1 to 2-week intervals up to 7.5 g/day.
• Maximum dose: 7.5 g/day

45 kg and greater:

• Initial dose: Up to 4.5 g orally per day, divided and given as 2 equal doses of up to 2.25 g/dose
• Maintenance dose: The dose may be increased by 1.5 g (OR 0.75 g/dose) orally per night at 1 to 2-week intervals up to 9 g/day.
• Maximum dose: 9 g/day

Comments:

• Patients who sleep more than 8 hours/night may be given the first dose at bedtime or after an initial period of sleep.
• Patients weighing less than 20 kg may be given lower initial, maximum, maintenance, and total maximum nightly doses.
• Unequal doses may be required in some patients to attain an optimal response to treatment.
• Both doses should be diluted at the same time at night.
• The first dose should be taken at bedtime and the other dose should be taken between 2.5 to 4 hours after; some may need to set an alarm to awaken to take the second dose.
• Patients should remain in bed after taking each dose.
• If the second dose is missed, patients should skip the dose and should not take this drug until the next night.
• Dosing may be gradually titrated, and doses should be determined by efficacy and tolerability.

Use: Treatment of cataplexy (excessive daytime sleepiness) in patients with narcolepsy

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Liver dysfunction:

• Initial dose: Half the original dose should be given, administered as 2 doses

Dose Adjustments

Transitioning from Sodium Oxybate:

• Initial dose: The same dose and regimen should be given (gram for gram)
• Dose titration may be administered as needed and tolerated.

Co-administration of Divalproex Sodium:
Patients already stabilized on this drug: The addition of divalproex sodium should be accompanied by an initial reduction in the nightly dose of this drug by at least 20%.

Patients already taking divalproex sodium:

• Initial dose: Healthcare providers should use a lower dose
• Maintenance dose: Healthcare providers should monitor patient response and adjust dose as needed.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for brand and generic versions of this drug. It includes a medication guide, elements to assure safe use, and implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
CENTRAL NERVOUS SYSTEM (CNS) DEPRESSION:

• This drug is a CNS depressant.
• In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in adult patients treated with this drug.
• Many patients who received this drug during clinical trials in narcolepsy and idiopathic hypersomnia were receiving CNS stimulants.

ABUSE AND MISUSE:

• This drug is the sodium salt of gamma-hydroxybutyrate (GHB).
• Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions (e.g., seizure, respiratory depression, decreased level of consciousness, coma, death).

RECOMMENDATION:

• Because of the risks of CNS depression and abuse and misuse, this drug is available only through a restricted REMS program.

CONTRAINDICATIONS:

• In combination with alcohol
• In combination with sedative hypnotic agents
• Patients with succinic semialdehyde dehydrogenase deficiency

Safety and efficacy have not been established in patients younger than 7 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance:

• Sodium oxybate: Schedule III
• GHB: Schedule I

Dialysis

Data not available

Other Comments

Administration advice:

• The first dose should be taken at least 2 to 3 hours after eating AND just before going to bed.
• The second dose should be taken between 2.5 to 4 hours after the first dose.
• Patients may need to set an alarm to awaken for the second dose.

Storage requirements:

• Keep out of reach of children.
• Any diluted doses remaining after 24 hours should be discarded.

Reconstitution/preparation techniques:

• Prepare both doses prior to bedtime.
• Prior to ingestion, each dose should be diluted with approximately 60 mL of water in the empty vials provided.

General:

• Physicians should evaluate patients for a history of or susceptibility to drug abuse prior to initiating therapy.
• During treatment, patients should be monitored for the risk of diversion, misuse and abuse.
• While many patients fall asleep within 5 to 15 minutes of taking this drug, others may take up to 2 hours to fall asleep.

Monitoring:

• NERVOUS SYSTEM: Signs/symptoms of excessive central nervous system depression
• OTHER: Withdrawal side effects (e.g., rebound insomnia), tolerance, dependence
• PSYCHIATRIC: Signs/symptoms of anxiety, emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior

Patient advice:

• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
• Patients should not drink alcohol or take other sedative hypnotics.
• Patients should remain in bed following ingestion of the first and second doses.
• Patients should not perform activities requiring complete mental alertness or motor co-ordination, such as operating machinery or driving.

Frequently asked questions

• How effective is Xywav for Idiopathic Hypersomnia?