Sodium oxybate
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE. • Central Nervous System Depression Xyrem (sodium oxybate) is a CNS depressant. In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in adult patients treated with Xyrem [see Warnings and Precautions ( 5.1 )]. Many patients who received Xyrem during clinical trials in narcolepsy were receiving central nervous system stimulants [see Clinical Trials ( 14 )]. • Abuse and Misuse Xyrem ® (sodium oxybate) 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, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )]. Because of the risks of CNS depression and abuse and misuse, Xyrem is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS [see Warnings and Precautions ( 5.3 )]. WARNING: CENTRAL NERVOUS SYSTEM (CNS) DEPRESSION and ABUSE AND MISUSE. See full prescribing information for complete boxed warning.
Central Nervous System Depression • Xyrem is a CNS depressant, and respiratory depression can occur with Xyrem use ( 5.1 , 5.4 ) Abuse and Misuse • Xyrem is the sodium salt of gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB is associated with CNS adverse reactions, including seizure, respiratory depression, decreased consciousness, coma, and death ( 5.2 , 9.2 ) Xyrem is available only through a restricted program called the XYWAV and XYREM REMS ( 5.3 )
Dosing in kidney impairment
High sodium content in Xyrem: Monitor patients with heart failure, hypertension, or impaired renal function. 5.1 Central Nervous System Depression Xyrem is a central nervous system (CNS) depressant. In adult clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in patients treated with Xyrem.
In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of Xyrem. Table 3 provides the approximate sodium content per Xyrem dose. Table 3 Approximate Sodium Content per Total Nightly Dose of Xyrem (g = grams) Xyrem Dose Sodium Content/Total Nightly Exposure 3 g per night 550 mg 4.5 g per night 820 mg 6 g per night 1100 mg 7.5 g per night 1400 mg 9 g per night 1640 mg
Dosing in liver impairment
Dosage Modification in Patients with Hepatic Impairment The recommended starting dosage in patients with hepatic impairment is one-half of the original dosage per night, administered orally divided into two doses [see Use in Specific Populations and Clinical Pharmacology] .
Preparation and administration
Important Administration Instructions for All Patients The total nightly dosage of Xyrem is divided into two doses. Prepare both doses of Xyrem prior to bedtime. Prior to ingestion, each dose of Xyrem should be diluted with approximately ¼ cup (approximately 60 mL) of water in the empty pharmacy containers provided. Take the first nightly dose of Xyrem at least 2 hours after eating [see Clinical Pharmacology] .
Take the second nightly dose 2.5 to 4 hours after the first dose. Patients should take both doses of Xyrem while in bed and lie down immediately after dosing, and remain in bed following ingestion of each dose. Xyrem may cause patients to fall asleep abruptly without first feeling drowsy [see Adverse Reactions] . Patients will often fall asleep within 5 minutes of taking Xyrem, and will usually fall asleep within 15 minutes, though the time it takes any individual patient to fall asleep may vary from night to night.
Patients may need to set an alarm to awaken for the second dose. Rarely, patients may take up to 2 hours to fall asleep. If the second dose is missed, that dose should be skipped and Xyrem should not be taken again until the next night. Both Xyrem doses should never be taken at one time.
Dosage Adjustment with Co-administration of Divalproex Sodium When initiating divalproex sodium in patients taking a stable dosage of Xyrem, a reduction of the Xyrem dosage by at least 20% is recommended with initial concomitant use [see Drug Interactions and Clinical Pharmacology] . When initiating Xyrem in patients already taking divalproex sodium, a lower starting dosage of Xyrem is recommended.
Subsequently, the dosage of Xyrem can be adjusted based on individual clinical response and tolerability.
Drug interactions
Check sodium oxybate against a medication listLabel text (3 paragraphs)
7 DRUG INTERACTIONS • Concomitant use with divalproex sodium: An initial reduction in Xyrem dose of at least 20% is recommended ( 2.5 , 7.2 ).
7.1 Alcohol, Sedative Hypnotics, and CNS Depressants Xyrem is contraindicated for use in combination with alcohol or sedative hypnotics. Use of other CNS depressants may potentiate the CNS-depressant effects of Xyrem [see Warnings and Precautions ( 5.1 )] .
7.2 Divalproex Sodium Concomitant use of Xyrem with divalproex sodium results in an increase in systemic exposure to GHB, which was shown to cause a greater impairment on some tests of attention and working memory in a clinical study [see Clinical Pharmacology ( 12.3 )] . An initial dose reduction of Xyrem is recommended when used concomitantly with divalproex sodium [see Dosage and Administration ( 2.5 )] . Prescribers are advised to monitor patient response closely and adjust dose accordingly if concomitant use of Xyrem and divalproex sodium is warranted.
Contraindications
Xyrem is contraindicated for use in: • combination with sedative hypnotics [see Warnings and Precautions ( 5.1 )] . • combination with alcohol [see Warnings and Precautions ( 5.1 )] . • patients with succinic semialdehyde dehydrogenase deficiency [see Clinical Pharmacology ( 12.3 )] . • In combination with sedative hypnotics or alcohol ( 4 ) • Succinic semialdehyde dehydrogenase deficiency ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of sodium oxybate in pregnant women. Oral administration of sodium oxybate to pregnant rats (150, 350, or 1,000 mg/kg/day) or rabbits (300, 600, or 1,200 mg/kg/day) throughout organogenesis produced no clear evidence of developmental toxicity; however, oral administration to rats throughout pregnancy and lactation resulted in increased stillbirths and decreased offspring postnatal viability and growth, at a clinically relevant dose [see Data] . In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Labor or Delivery Xyrem has not been studied in labor or delivery. In obstetric anesthesia using an injectable formulation of sodium oxybate, newborns had stable cardiovascular and respiratory measures but were very sleepy, causing a slight decrease in Apgar scores. There was a fall in the rate of uterine contractions 20 minutes after injection.
Placental transfer is rapid and gamma-hydroxybutyrate (GHB) has been detected in newborns at delivery after intravenous administration of GHB to mothers. Subsequent effects of sodium oxybate on later growth, development, and maturation in humans are unknown. Data Animal Data Oral administration of sodium oxybate to pregnant rats (150, 350, or 1,000 mg/kg/day) or rabbits (300, 600, or 1,200 mg/kg/day) throughout organogenesis produced no clear evidence of developmental toxicity. The highest doses tested in rats and rabbits were approximately 1 and 3 times, respectively, the maximum recommended human dose (MRHD) of 9 g per night on a body surface area (mg/m 2 ) basis.
Oral administration of sodium oxybate (150, 350, or 1,000 mg/kg/day) to rats throughout pregnancy and lactation resulted in increased stillbirths and decreased offspring postnatal viability and body weight gain at the highest dose tested. The no-effect dose for pre- and post-natal developmental toxicity in rats is less than the MRHD on a mg/m 2 basis.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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