calcium, magnesium, potassium, and sodium oxybates

General Information

Calcium, magnesium, potassium, and sodium oxybates (Xywav) is a nighttime medication indicated for cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy, and for idiopathic hypersomnia (IH) in adults (label).

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

Compared with sodium oxybate (Xyrem), Xywav provides a substantially lower sodium load at equivalent oxybate doses. This is clinically relevant for patients with cardiovascular comorbidity (hypertension, heart failure) or other situations where sodium restriction is a counseling priority (label/clinical).

Implementation is often the limiting factor: nightly preparation, dosing while in bed, avoidance of alcohol and other sedatives, and safe storage (to reduce diversion) are core practical requirements (label/clinical).

The Xywav compare view, evidence feed, and print page support shared decision-making across oxybate formulations and alternatives.

Xywav is often considered when oxybate is clinically attractive but sodium burden is a concern (e.g., hypertension, heart failure). As with other oxybate products, the required REMS, strict avoidance of alcohol/sedatives, and safe nighttime routines commonly determine feasibility and drive follow-up intensity (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 in narcolepsy, and improvements in daytime sleepiness and sleep inertia patterns in IH when titrated to an effective regimen (label/clinical).

Because sedation can occur quickly after dosing, safety planning prioritizes 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; on average, <5% of unchanged drug appears in urine within 6 to 8 hours after dosing (label).
• Mean terminal elimination half-life is ~0.66 hours; hepatic impairment increases exposure and prolongs half-life (label).
• Food reduces absorption; administration is separated from meals (first dose at least 2 hours after eating) (label).

Dosing and Administration

• Narcolepsy (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 per night or single doses above 6 g are not recommended (label).
• Idiopathic hypersomnia (adults): Xywav can be administered as a once-nightly or twice-nightly regimen. Regimen selection often aligns with sleep inertia/long sleep time (consider once nightly) versus disrupted nocturnal sleep/sleep maintenance complaints (consider twice nightly), and can be adjusted during titration based on efficacy and tolerability (label/clinical).
• Prepare doses before bedtime and dilute with water; for twice-nightly dosing, the second dose is taken 2.5–4 hours after the first (label).
• Take the first dose at least 2 hours after eating; 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).
• Mood and neuropsychiatric symptom monitoring (label/clinical).
• Hepatic impairment assessment for dosing and safety (label).
• Review of interaction with divalproex/valproate if co-prescribed and confirm dose reduction (label/clinical).

Adverse Effects

Interactions

• Alcohol and sedative-hypnotics are avoided due to additive CNS depression and respiratory depression risk (label).
• Concomitant divalproex/valproate increases oxybate exposure and cognitive impairment signals; reduce Xywav dose by at least 20% when used together with close monitoring (label).
• Other CNS depressants (benzodiazepines, opioids, sedating antidepressants, some antipsychotics) increase sedation/respiratory risk; polypharmacy review is a routine safety step (label/clinical).

Other Useful Information

• Xywav contains less sodium than sodium oxybate (Xyrem) at equivalent oxybate doses; clinicians often consider overall sodium burden when patients have hypertension, heart failure, kidney disease, or other cardiovascular risk factors (label/clinical).
• Implementation topics (REMS enrollment, dose preparation, split-night alarms when applicable, safe storage, and avoidance of alcohol/sedatives) are often reviewed explicitly at initiation and during titration (label/clinical).
• When obstructive sleep apnea is untreated or opioids are required, clinicians commonly reassess whether an oxybate product is appropriate given respiratory depression risk (clinical).

References

1. XYWAV (calcium, magnesium, potassium, and sodium oxybates) 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. Efficacy AND Safety OF Calcium, Magnesium, Potassium, AND Sodium Oxybates (lower Sodium Oxybate [lxb]; JZP 258) IN A Placebo Controlled, Double Blind, Randomized Withdrawal Study IN Adults With Narcolepsy With Cataplexy — Sleep (2020)
5. Calcium, Magnesium, Potassium, AND Sodium Oxybates Oral Solution: A Lower Sodium Alternative FOR Cataplexy OR Excessive Daytime Sleepiness Associated With Narcolepsy — Nature and Science of Sleep (2022)