Section 10 · Monograph

Sodium oxybate

Reviewed Nov 2026FDA label

Xyrem / XywavGABA-B agonist

Black Box Warning

CNS DEPRESSION: Sodium oxybate is a CNS depressant. Clinically significant respiratory depression and decreased levels of consciousness (obtundation) have occurred at recommended doses. Concomitant use with other CNS depressants (opioids, benzodiazepines, sedative-hypnotics, alcohol) increases risk of respiratory depression and death.
ABUSE AND MISUSE: The active moiety is oxybate, also known as gamma-hydroxybutyrate (GHB), a Schedule III controlled substance subject to abuse and misuse. Because of these risks, Xyrem and Xywav are available only through a restricted distribution program, the Xywav and Xyrem REMS program — prescribers must be certified, drugs dispensed only through a single central pharmacy, patients enrolled and counseled on safe use.

Treatment of cataplexy in patients 7 years of age and older with narcolepsy (both Xyrem and Xywav).FDA-labeled
Treatment of excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy (both Xyrem and Xywav).FDA-labeled
Treatment of idiopathic hypersomnia in adults — Xywav only (Xyrem does not carry this indication).FDA-labeled
PRODUCT DISTINCTION: Xyrem (sodium oxybate) and Xywav (calcium, magnesium, potassium, and sodium oxybates) are both oxybate (GHB) salt formulations from the same manufacturer with essentially the same active moiety but different cation compositions. Xywav contains ~92% less sodium than Xyrem at the maximum recommended nightly dose, clinically relevant for patients with hypertension, cardiovascular disease, or renal disease. Both are dosed by the same oxybate gram-equivalent amounts and share essentially the same efficacy, safety, boxed warning, and REMS requirements.FDA-labeled

Sodium oxybate/oxybate salts are the sodium salt (Xyrem) or a mixture of calcium, magnesium, potassium, and sodium salts (Xywav) of gamma-hydroxybutyrate (GHB), an endogenous CNS compound structurally related to GABA.
Precise mechanism of therapeutic effect in narcolepsy and idiopathic hypersomnia is unknown.
Hypothesized to act via GABA-B receptor agonism, particularly during sleep, at CNS sites including the thalamus, hippocampus, and other regions involved in sleep architecture regulation.
Oxybate consolidates nighttime sleep and increases slow-wave (deep) sleep, believed to underlie improvement in both EDS and cataplexy.
Distinct pharmacologically from all other narcolepsy medications — administered at night, targets nighttime sleep quality rather than direct daytime wake-promotion, and is the only agent with robust cataplexy efficacy along with pitolisant.

Both products taken orally, divided into two doses per night: first dose at bedtime (while already in bed) and second dose 2.5-4 hours later; each dose at least 2 hours after eating.
Adults with narcolepsy, oxybate-naive: starting total nightly dose 4.5 g/night (divided into two 2.25 g doses); may titrate by up to 1.5 g/night at intervals of at least 1 week; usual effective range 6-9 g/night (maximum 9 g/night).
Xywav-specific idiopathic hypersomnia dosing (adults, oxybate-naive): once nightly (start 4.5 g, titrate to max 6 g) or twice nightly (start 3 g/night divided, titrate to max 9 g/night) — once-nightly option unique to Xywav for IH.
Patients switching between Xyrem and Xywav can generally be switched at the same total gram dose given equivalent oxybate content.
Concomitant divalproex sodium: increases oxybate exposure by ~25%; consider reducing oxybate dose by at least 20%.

Renal impairment: no formal dose adjustment established but caution/consider lower sodium formulation (Xywav) if sodium restriction relevant.

Hepatic impairment (Child-Pugh B or C): halve the starting dose and titrate more cautiously.

Pediatric patients (7 years and older) with narcolepsy: weight-based dosing regimens with lower starting doses and slower titration than adults; maximum dose generally capped at 9 g/night (lower caps for lower weight bands).

Concomitant use with sedative hypnotics, or with alcohol.
Patients with succinic semialdehyde dehydrogenase (SSADH) deficiency — oxybate is contraindicated as it can precipitate severe metabolic/neurologic toxicity.

CNS depressants (opioids, benzodiazepines and other sedative-hypnotics, alcohol, general anesthetics, TCAs, other muscle relaxants): additive CNS and respiratory depression — avoid combination; alcohol is contraindicated.
Divalproex sodium (valproate): increases oxybate systemic exposure by ~25%; reduce oxybate dose by at least 20% if used concomitantly.
Other sodium-containing medications: additional sodium load with Xyrem may be clinically relevant in patients on sodium-restricted diets or with hypertension, heart failure, or renal impairment — consider Xywav preferentially.
Drugs affecting CNS depressant thresholds generally (gabapentinoids) — increased risk of additive sedation.

Adults, most common (≥5%): nausea, dizziness, vomiting, somnolence, enuresis, tremor; Xywav additionally reports headache, anxiety, decreased appetite, hyperhidrosis, diarrhea, dry mouth, parasomnia, fatigue.
Pediatric patients (≥5%): nausea, enuresis, vomiting, headache, decreased weight, decreased appetite, dizziness, and sleepwalking.
Respiratory depression, especially with concomitant CNS depressants, in patients with compromised respiratory function, or with rapid dose escalation.
Parasomnias, enuresis/incontinence, and confusion/disorientation, particularly during initial titration.
Depression and suicidal ideation reported.
Abuse, misuse, diversion, and physical dependence/withdrawal.
Increased blood pressure has been reported, more commonly with higher-sodium Xyrem.
Rare: eating disorder/sleep-related eating; obstructive/central sleep apnea exacerbation.

Respiratory status, especially at treatment initiation, during dose titration, and with pre-existing respiratory disease, obesity, or concomitant CNS depressant use.
Screen for and counsel against concurrent use of alcohol or other CNS depressants at every visit.
Mental health/mood — monitor for depression, anxiety, and suicidal ideation.
Blood pressure periodically, particularly on Xyrem or with cardiovascular/renal comorbidities.
Weight and BMI, especially in pediatric patients.
Assess for signs of misuse, diversion, tolerance, or dependence; REMS-mandated patient counseling.
Screen for sleep-disordered breathing/OSA at baseline.
Renal and hepatic function as clinically indicated.

Pregnancy: Data are insufficient to establish a drug-associated risk of major birth defects or miscarriage. Animal reproduction studies did not show developmental toxicity during organogenesis at clinically relevant exposures, but increased stillbirths were observed at the highest doses tested.
Lactation: GHB is excreted into human milk. Insufficient information on effects on the breastfed infant; a decision should be made whether to discontinue breastfeeding or discontinue the drug, monitoring the infant for excess sedation or poor feeding if breastfeeding is continued.