Sodium Oxybate
FDA Drug Information • Also known as: Lumryz, Sodium Oxybate, Xyrem
- Brand Names
- Lumryz, Sodium Oxybate, Xyrem
- Route
- ORAL
- Dosage Form
- FOR SUSPENSION, EXTENDED RELEASE
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE.
Central Nervous System Depression Sodium Oxybate Oral Solution is a CNS depressant. In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in adult patients treated with Sodium Oxybate Oral Solution [see Warnings and Precautions ( 5.1 )]. Many patients who received Sodium Oxybate Oral Solution during clinical trials in narcolepsy were receiving central nervous system stimulants [see Clinical Trials ( 14 )]. Abuse and Misuse 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, Sodium Oxybate Oral Solution 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 Sodium Oxybate Oral Solution is a CNS depressant, and respiratory depression can occur with Sodium Oxybate Oral Solution use ( 5.1 , 5.4 ) Abuse and Misuse Sodium Oxybate 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 ) Sodium Oxybate Oral Solution is available only through a restricted program called the XYWAV and XYREM REMS ( 5.3 )Description
11 DESCRIPTION Sodium oxybate, a CNS depressant, is the active ingredient in Sodium Oxybate Oral Solution. The chemical name for sodium oxybate is sodium 4‑hydroxybutyrate. The molecular formula is C 4 H 7 NaO 3 , and the molecular weight is 126.09 g/mole. The chemical structure is: Sodium oxybate is a white to off-white, crystalline powder that is very soluble in aqueous solutions. Each mL of Sodium Oxybate Oral Solution contains 0.5 g of sodium oxybate (equivalent to 0.413 g/mL of oxybate) in USP Purified Water, neutralized to pH 7.5 with malic acid. chemical structure
What Is Sodium Oxybate Used For?
1 INDICATIONS AND USAGE Sodium Oxybate Oral Solution is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. Sodium Oxybate Oral Solution is a central nervous system depressant indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Dosage for Adult Patients
Initiate dosage at 4.5 g per night orally, divided into two doses ( 2.1 ). Titrate to effect in increments of 1.5 g per night at weekly intervals (0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later) ( 2.1 ). Recommended dosage range: 6 g to 9 g per night orally ( 2.1 ). Total Nightly Dose Take at Bedtime Take 2.5 to 4 Hours Later 4.5 g per night 2.25 g 2.25 g 6 g per night 3 g 3 g 7.5 g per night 3.75 g 3.75 g 9 g per night 4.5 g 4.5 g Dosage for Pediatric Patients (7 years of Age and Older) The recommended starting dosage, titration regimen, and maximum total nightly dosage are based on body weight ( 2.2 ). Important Administration Information Prepare both doses prior to bedtime; dilute each dose with approximately ¼ cup of water in pharmacy-provided containers ( 2.3 ). Allow 2 hours after eating before dosing ( 2.3 ). Take each dose while in bed and lie down after dosing ( 2.3 ). Patients with Hepatic Impairment Recommended starting dosage is one-half of the original dosage per night administered orally, divided into two doses ( 2.4 ). 2.1 Adult Dosing Information The recommended starting dosage is 4.5 grams (g) per night administered orally, divided into two doses: 2.25 g at bedtime and 2.25 g taken 2.5 to 4 hours later (see Table 1). Increase the dosage by 1.5 g per night at weekly intervals (additional 0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later) to the effective dosage range of 6 g to 9 g per night orally. The dosage may be gradually titrated based on efficacy and tolerability. Doses higher than 9 g per night have not been studied and should not ordinarily be administered. Table 1: Recommended Adult Sodium Oxybate Oral Solution Dose Regimen (g = grams) If a Patient’s Total Nightly Dose is: Take at Bedtime: Take 2.5 to 4 Hours Later: 4.5 g per night 2.25 g 2.25 g 6 g per night 3 g 3 g 7.5 g per night 3.75 g 3.75 g 9 g per night 4.5 g 4.5 g 2.2 Pediatric Dosing Information Sodium Oxybate Oral Solution is administered orally twice nightly. The recommended starting pediatric dosage, titration regimen, and maximum total nightly dosage are based on patient weight, as specified in Table 2. The dosage may be gradually titrated based on efficacy and tolerability. Table 2: Recommended Pediatric Sodium Oxybate Oral Solution Dosage for Patients 7 Years of Age and Older* Patient Weight Initial Dosage Maximum Weekly Dosage Increase Maximum Recommended Dosage Take at Bedtime: Take 2.5 to 4 Hours Later: Take at Bedtime: Take 2.5 to 4 Hours Later: Take at Bedtime: Take 2.5 to 4 Hours Later: <20 kg ** There is insufficient information to provide specific dosing recommendations for patients who weigh less than 20 kg. 20 kg to <30 kg ≤1 g ≤1 g 0.5 g 0.5 g 3 g 3 g 30 kg to <45 kg ≤1.5 g ≤1.5 g 0.5 g 0.5 g 3.75 g 3.75 g ≥45 kg ≤2.25 g ≤2.25 g 0.75 g 0.75 g 4.5 g 4.5 g *For patients who sleep more than 8 hours per night, the first dose of Sodium Oxybate Oral Solution may be...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions appear in other sections of the labeling:
CNS depression [see Warnings and Precautions ( 5.1 )] Abuse and Misuse [see Warnings and Precautions ( 5.2 )] Respiratory Depression and Sleep-Disordered Breathing [see Warnings and Precautions ( 5.4 )] Depression and Suicidality [see Warnings and Precautions ( 5.5 )] Other Behavioral or Psychiatric Adverse Reactions [see Warnings and Precautions ( 5.6 )] Parasomnias [see Warnings and Precautions ( 5.7 )] Use in Patients Sensitive to High Sodium Intake [see Warnings and Precautions ( 5.8 )] Most common adverse reactions in adults (≥5% and at least twice the incidence with placebo) were nausea, dizziness, vomiting, somnolence, enuresis, and tremor ( 6.1 ). Most common adverse reactions in pediatric patients (≥5%) were nausea, enuresis, vomiting, headache, weight decreased, decreased appetite, dizziness, and sleepwalking ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1-800-520-5568, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adult Patients Sodium Oxybate Oral Solution was studied in three placebo-controlled clinical trials (Trials N1, N3, and N4, described in Sections 14.1 and 14.2) in 611 patients with narcolepsy (398 subjects treated with Sodium Oxybate Oral Solution, and 213 with placebo). A total of 781 patients with narcolepsy were treated with Sodium Oxybate Oral Solution in controlled and uncontrolled clinical trials. Section 6.1 and Table 4 present adverse reactions from three pooled, controlled trials (N1, N3, N4) in patients with narcolepsy. Adverse Reactions Leading to Treatment Discontinuation: Of the 398 patients with narcolepsy treated with Sodium Oxybate Oral Solution, 10.3% of patients discontinued because of adverse reactions compared with 2.8% of patients receiving placebo. The most common adverse reaction leading to discontinuation was nausea (2.8%). The majority of adverse reactions leading to discontinuation began during the first few weeks of treatment. Commonly Observed Adverse Reactions in Controlled Clinical Trials: The most common adverse reactions (incidence ≥5% and twice the rate seen with placebo) in patients treated with Sodium Oxybate Oral Solution were nausea, dizziness, vomiting, somnolence, enuresis, and tremor. Adverse Reactions Occurring at an Incidence of 2% or Greater: Table 4 lists adverse reactions that occurred at a frequency of 2% or more in any treatment group for three controlled trials and were more frequent in any Sodium Oxybate Oral Solution treatment group than with placebo. Adverse reactions are summarized by dose at onset. Nearly all patients in these studies initiated treatment at 4.5 g per night. In patients who remained on treatment, adverse reactions tended to occur early and to diminish over time. Table 4 Adverse Reactions Occurring in ≥2% of Adult Patients and More Frequently with Sodium Oxybate Oral Solution than Placebo in Three Controlled Trials (N1, N3, N4) by Body System and Dose at Onset Adverse Reaction Placebo (n=213) % Sodium Oxybate Oral Solution 4.5g (n=185) % Sodium Oxybate Oral Solution 6g (n=258) % Sodium Oxybate Oral Solution 9g (n=178) % ANY ADVERSE REACTION 62 45 55 70 GASTROINTESTINAL DISORDERS Nausea 3 8 13 20 Vomiting 1 2 4 11 Diarrhea 2 4 3 4 Abdominal pain upper 2 3 1 2 Dry mouth 2 1 2 1 GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS Pain 1 1 <1 3 Feeling drunk 1 0 <1 3 Edema peripheral 1 3 0 0 MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS Cataplexy 1 1 1 2 Muscle spasms 2 2 <1 2 Pain in extremity 1 3 1 1 NERVOUS SYSTEM DISORDERS Dizziness 4 9 11 15 Somnolence 4 1 3 8...Drug Interactions
7 DRUG INTERACTIONS
Concomitant use with divalproex sodium: An initial reduction in Sodium Oxybate Oral Solution dose of at least 20% is recommended ( 2.5 , 7.2 ). 7.1 Alcohol, Sedative Hypnotics, and CNS Depressants Sodium Oxybate Oral Solution is contraindicated for use in combination with alcohol or sedative hypnotics. Use of other CNS depressants may potentiate the CNS-depressant effects of Sodium Oxybate Oral Solution [see Warnings and Precautions ( 5.1 )]. 7.2 Divalproex Sodium Concomitant use of Sodium Oxybate Oral Solution 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 Sodium Oxybate Oral Solution 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 Sodium Oxybate Oral Solution and divalproex sodium is warranted.Contraindications
4 CONTRAINDICATIONS Sodium Oxybate Oral Solution 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 Breastfeeding
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 Sodium Oxybate Oral Solution 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...
Overdosage
10 OVERDOSAGE 10.1 Human Experience Information regarding overdose with Sodium Oxybate Oral Solution is derived largely from reports in the medical literature that describe symptoms and signs in individuals who have ingested GHB illicitly. In these circumstances the co-ingestion of other drugs and alcohol was common, and may have influenced the presentation and severity of clinical manifestations of overdose. In adult clinical trials two cases of overdose with Sodium Oxybate Oral Solution were reported. In the first case, an estimated dose of 150 g, more than 15 times the maximum recommended dose, caused a patient to be unresponsive with brief periods of apnea and to be incontinent of urine and feces. This individual recovered without sequelae. In the second case, death was reported following a multiple drug overdose consisting of Sodium Oxybate Oral Solution and numerous other drugs. 10.2 Signs and Symptoms Information about signs and symptoms associated with overdosage with Sodium Oxybate Oral Solution derives from reports of illicit use of GHB. Patient presentation following overdose is influenced by the dose ingested, the time since ingestion, the co‑ingestion of other drugs and alcohol, and the fed or fasted state. Patients have exhibited varying degrees of depressed consciousness that may fluctuate rapidly between a confusional, agitated combative state with ataxia and coma. Emesis (even when obtunded), diaphoresis, headache, and impaired psychomotor skills have been observed. No typical pupillary changes have been described to assist in diagnosis; pupillary reactivity to light is maintained. Blurred vision has been reported. An increasing depth of coma and acidosis have been observed at higher doses. Myoclonus and tonic-clonic seizures have been reported. Respiration may be unaffected or compromised in rate and depth. Cheyne‑Stokes respiration and apnea have been observed. Bradycardia and hypothermia may accompany unconsciousness, as well as muscular...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Sodium Oxybate Oral Solution is a clear to slightly opalescent oral solution. Each prescription includes one bottle of Sodium Oxybate Oral Solution with attached press in bottle adaptor, an oral measuring device (plastic syringe), and a Medication Guide. The pharmacy provides two empty containers with child-resistant caps with each Sodium Oxybate Oral Solution shipment. Each amber bottle contains Sodium Oxybate Oral Solution at a concentration of 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate) and has a child-resistant cap. One 180 mL bottle NDC 0054-9628-57 16.2 Storage Keep out of reach of children. Sodium Oxybate Oral Solution should be stored at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature). Dispense in tight containers. Solutions prepared following dilution should be consumed within 24 hours. 16.3 Handling and Disposal Sodium Oxybate Oral Solution is a Schedule III drug under the Controlled Substances Act. Sodium Oxybate Oral Solution should be handled according to state and federal regulations. It is safe to dispose of Sodium Oxybate Oral Solution down the sanitary sewer. 16.1 How Supplied Sodium Oxybate Oral Solution is a clear to slightly opalescent oral solution. Each prescription includes one bottle of Sodium Oxybate Oral Solution with attached press in bottle adaptor, an oral measuring device (plastic syringe), and a Medication Guide. The pharmacy provides two empty containers with child-resistant caps with each Sodium Oxybate Oral Solution shipment. Each amber bottle contains Sodium Oxybate Oral Solution at a concentration of 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate) and has a child-resistant cap. One 180 mL bottle NDC 0054-9628-57
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.