sodium oxybate

General Information

Sodium oxybate (Xyrem) is a nighttime medication indicated for cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy (label).

It is a CNS depressant and a Schedule III controlled substance with a boxed warning for CNS depression and abuse/misuse; it is dispensed only through a REMS due to risk of respiratory depression and misuse (label).

Dosing is split into two doses each night (bedtime and 2.5 to 4 hours later). Many patients fall asleep quickly after dosing, so fall risk, safe storage, and nighttime environment planning are core counseling topics (label/clinical).

Alcohol and sedatives increase respiratory depression risk and are generally avoided; interaction review is especially important in polypharmacy and in patients with substance use disorders (label/clinical).

The sodium oxybate compare view, evidence feed, and print page support review of wake-promoting strategies and implementation constraints.

Sodium oxybate can meaningfully improve cataplexy and daytime sleepiness in narcolepsy, but implementation burden (split-night dosing, REMS, avoidance of alcohol/sedatives, safe storage) often determines feasibility in practice (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Oxybate (GHB) is a CNS depressant. Clinical framing emphasizes nighttime consolidation of sleep and downstream improvements in cataplexy and EDS when titrated to an effective dose (label/clinical).

Because of abrupt sleep onset after dosing, safety planning focuses on taking doses while in bed and avoiding hazardous activities after dosing (label/clinical).

• CNS depressant (oxybate/GHB; mechanism related to sleep consolidation).

Metabolism and Pharmacokinetics

• Clearance is almost entirely by biotransformation to carbon dioxide, which is eliminated by expiration; <5% of unchanged drug appears in urine within 6 to 8 hours after dosing (label).
• Elimination half-life is ~0.5–1 hour; hepatic impairment prolongs half-life and increases exposure (label).
• Food reduces absorption; administration is separated from meals (first dose at least 2 hours after eating) (label).

Dosing and Administration

• Adults: start 4.5 g per night in two doses (2.25 g at bedtime and 2.25 g 2.5–4 hours later). Titrate by 1.5 g per night at weekly intervals to an effective range of 6–9 g per night; doses above 9 g are not ordinarily administered (label).
• Prepare both doses before bedtime and dilute each dose with water in pharmacy-provided containers; take the second dose 2.5–4 hours after the first (label).
• Take the first dose at least 2 hours after eating; the second dose is taken 2.5–4 hours after the first dose (label).
• Patients often fall asleep within minutes after dosing; dosing is taken while in bed and staying in bed after dosing is emphasized to reduce fall risk (label/clinical).

Monitoring & Labs

• Respiratory risk and CNS depressant co-medication review (label/clinical).
• Safe storage and misuse/diversion monitoring consistent with REMS (label/clinical).
• Nighttime fall risk assessment and environment planning (clinical).
• Hepatic impairment assessment for dosing and safety (label).
• Review of interaction with divalproex/valproate if co-prescribed (label/clinical).

Adverse Effects

Interactions

• Alcohol and sedative-hypnotics are generally avoided due to additive CNS depression and respiratory depression risk (label).
• Concomitant divalproex/valproate increases exposure; an initial dose reduction of at least 20% is recommended with close monitoring (label).
• Other CNS depressants (benzodiazepines, opioids, some antipsychotics, sedating antidepressants) can increase sedation and respiratory risk; careful review is a routine safety step (label/clinical).

Other Useful Information

• Evidence syntheses and guidelines support oxybate for narcolepsy symptom control, but implementation constraints (split dosing, REMS, sedation risk) often determine feasibility (AASM/clinical).
• In serious mental illness, clinicians often coordinate dosing plans with co-medications, housing stability, and safety supports to reduce fall risk and ensure adherence (clinical).

References

1. XYREM (sodium oxybate) oral solution prescribing information — DailyMed (2025)
2. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline — Journal of Clinical Sleep Medicine (2021)
3. Treatment OF Central Disorders OF Hypersomnolence: AN American Academy OF Sleep Medicine Systematic Review, Meta Analysis, AND Grade Assessment — Journal of Clinical Sleep Medicine (2021)
4. Sodium oxybate improves excessive daytime sleepiness in narcolepsy — Sleep (2006)