sodium oxybate .5 g/mL Solution — NDC 72865-349-18 (Billing 72865-0349-18)
This is a package of sodium oxybate .5 g/mL Solution from XLCare Pharmaceuticals, Inc., marketed since Jan 2026 and currently FDA-listed. It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
- RxCUI (RxNorm): 349482
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Central Nervous System Depressant class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Calcium, magnesium, potassium, and sodium oxybate is used to treat attacks of cataplexy (episodes of muscle weakness that begin suddenly and last for a short time) and excessive daytime sleepiness in adults and children 7 years of age and older who have narcolepsy (a sleep disorder that may cause extreme sleepiness, sudden uncontrollable urge to sleep during daily activities, and cataplexy). Calcium, magnesium, potassium, and sodium oxybate is also used to treat adults who have idiopathic hypersomnia (IH; a sleep disorder that may cause excessive daytime sleepiness and uncontrollable urge to s...
Read the full MedlinePlus article ↗- That's a great question, and the answer depends on which product you're prescribed. If you're on Xyrem or the generic oral solution, yes — you do need two doses spaced about 2.5 to...
- Why do I have to take two doses in the middle of the night — can't I just take it all at once?
- No — alcohol and sodium oxybate absolutely cannot be mixed, even if there are hours between them. Combining the two dramatically increases the risk of your breathing slowing down d...
- Can I have a glass of wine with dinner if I take my dose hours later at bedtime?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Sodium Oxybate — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $33.52 | $6,033.69 / 180 ml |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 3, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 72865-0349-18 You're viewing this Main listing | 1 BOTTLE in 1 CARTON / 180 mL in 1 BOTTLE | 2026-01-01 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| sodium oxybate .5 g/mL 00054-9628-57 | Hikma | 180 ml | — | AA | FDA listed | — |
| sodium oxybate .5 g/mL 31722-0891-18 | Camber | 1 bottle | — | AA | FDA listed | — |
| Sodium Oxybate 500 mg/mL 65162-0065-87 | Amneal | 1 bottle | — | AA | FDA listed | — |
| Xyrem .5 g/mL 68727-0100-01 | Jazz | 180 ml | — | AA | FDA listed | — |
| sodium oxybate .5 g/mLthis 72865-0349-18 | XLCare | 1 bottle | — | AA | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 817L1N4CKP
Malic acid is a naturally occurring organic acid found in fruits. It works as a buffer and flavor agent to maintain the medicine's pH balance and add tartness to the product.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
2 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CENTRAL NERVOUS SYSTEM (CNS) DEPRESSION and ABUSE AND MISUSE. Central Nervous System Depression Sodium oxybate 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 Sodium Oxybate REMS Program [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 oral solution 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 Sodium Oxybate REMS Program (5.3)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Sodium oxybate oral solution is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy. Pediatric use information is approved for Jazz Pharmaceuticals Inc.’s XYREM (sodium oxybate) Oral Solution. However, due to Jazz Pharmaceuticals Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Sodium oxybate oral solutio n is a central nervous system depressant indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 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 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 ).
2.1Adult 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 Pediatric use information is approved for Jazz Pharmaceuticals Inc.’s XYREM (sodium oxybate) Oral Solution. However, due to Jazz Pharmaceuticals Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
2.3Important Administration Instructions for All Patients The total nightly dosage of sodium oxybate oral solution is divided into two doses. Prepare both doses of sodium oxybate oral solution prior to bedtime. Prior to ingestion, each dose of sodium oxybate oral solution should be diluted with approximately ¼ cup (approximately 60 mL) of water in the empty pharmacy containers provided.
Take the first nightly dose of sodium oxybate oral solution at least 2 hours after eating [see Clinical Pharmacology (12.3)]. Take the second nightly dose 2.5 to 4 hours after the first dose. Patients should take both doses of sodium oxybate oral solution while in bed and lie down immediately after dosing, and remain in bed following ingestion of each dose.
Sodium oxybate oral solution may cause patients to fall asleep abruptly without first feeling drowsy [see Adverse Reactions (6.2)]. Patients will often fall asleep within 5 minutes of taking sodium oxybate oral solution, 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 sodium oxybate oral solution should not be taken again until the next night. Both sodium oxybate oral solution doses should never be taken at one time.
2.4Dosage 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 (8.6) and Clinical Pharmacology (12.3)].
2.5Dosage Adjustment with Co-administration of Divalproex Sodium When initiating divalproex sodium in patients taking a stable dosage of sodium oxybate oral solution, a reduction of the sodium oxybate oral solution dosage by at least 20% is… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Sodium oxybate oral solution is a clear to slightly opalescent oral solution, in a concentration of 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate). Oral solution, 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate) (3)
⛔ 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS CNS depression: Use caution when considering the concurrent use of sodium oxybate oral solution with other CNS depressants (5.1). Caution patients against hazardous activities requiring complete mental alertness or motor coordination within the first 6 hours of dosing or after first initiating treatment until certain that sodium oxybate oral solution does not affect them adversely (5.1). Depression and suicidality: Monitor patients for emergent or increased depression and suicidality (5.5).
Confusion/Anxiety: Monitor for impaired motor/cognitive function (5.6). Parasomnias: Evaluate episodes of sleepwalking (5.7). High sodium content in sodium oxybate oral solution: Monitor patients with heart failure, hypertension, or impaired renal function (5.8).
5.1Central Nervous System Depression Sodium oxybate 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 sodium oxybate oral solution. Sodium oxybate oral solution is contraindicated in combination with alcohol and sedative hypnotics.
The concurrent use of sodium oxybate oral solution with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If use of these CNS depressants in combination with sodium oxybate oral solution is required, dose reduction or discontinuation of one or more CNS depressants (including sodium oxybate oral solution) should be considered.
In addition, if short-term use of an opioid (e.g., post- or perioperative) is required, interruption of treatment with sodium oxybate oral solution should be considered. Healthcare providers should caution patients about operating hazardous machinery, including automobiles or airplanes, until they are reasonably certain that sodium oxybate oral solution does not affect them adversely (e.g., impair judgment, thinking, or motor skills). Patients should not engage in hazardous occupations or activities requiring complete mental alertness or motor coordination, such as operating machinery or a motor vehicle or flying an airplane, for at least 6 hours after taking sodium oxybate oral solution.
Patients should be queried about CNS depression-related events upon initiation of sodium oxybate oral solution therapy and periodically thereafter. Sodium oxybate oral solution is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)].
5.2Abuse and Misuse Sodium oxybate oral solution is a Schedule III controlled substance. The active ingredient of sodium oxybate oral solution, sodium oxybate or gamma-hydroxybutyrate (GHB), is a Schedule I controlled substance. Abuse 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.
The rapid onset of sedation, coupled with the amnestic features of sodium oxybate oral solution, particularly when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user (e.g., assault victim). Because illicit use and abuse of GHB have been reported, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of GHB (e.g., increase in size or frequency of dosing, drug-seeking behavior, feigned cataplexy) [see Drug Abuse and Dependence (9.2)].
Sodium oxybate oral solution is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)].
5.3Sodium Oxybate REMS Program Sodium oxybate oral solution is available only through a restricted d… [Excerpted — this section continues on DailyMed.]
🤒 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).
To report SUSPECTED ADVERSE REACTIONS, contact XLCare Pharmaceuticals, Inc. at 1-866-495-1995, or FDA at 1-800-FDA-1088 or www.fda.gov/Medwatch.
6.1Clinical 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 Tremor 0 0 2 5 Disturbance in attention 0 1 0 4 Paresthesia 1 2 1 3 Sleep paralysis 1 0 1 3 PSYCHIATRIC DISORDERS Disorientation 1 1 2 3 Irritability 1 0 <1 3 Sleepwalking 0 0 0 3 Anxiety 1 1 1 2 RENAL AND UR… [Excerpted — this section continues on DailyMed.]
🔄 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).
7.1Alcohol, 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)].
7.2Divalproex 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ). Geriatric patients: Monitor for impaired motor and/or cognitive function when taking sodium oxybate oral solution ( 8.5 ). Pediatric use information is approved for Jazz Pharmaceuticals Inc.’s XYREM (sodium oxybate) Oral Solution.
However, due to Jazz Pharmaceuticals Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
8.1Pregnancy 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 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 postnatal developmental toxicity in rats is less than the MRHD on a mg/m 2 basis.
8.2Lactation Risk Summary GHB is excreted in human milk after oral administration of sodium oxybate. There is insufficient information on the risk to a breastfed infant, and there is insufficient information on milk production in nursing mothers. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sodium oxybate oral solution and any potential adverse effects on the breastfed infant from sodium oxybate oral solution or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness of sodium oxybate oral solution in pediatric patients below the age of 7 years have not been established. Juvenile Animal Toxicity Data In a study in which sodium oxybate (0, 100, 300, or 900 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 21 through 90), mortality was observed at the two highest doses tested. Deaths occurred during the first week of dosing and were associated with clinical signs (including decreased activity and respiratory rate) consistent with the pharmacological effects of the drug.
Reduced body weight gain in males and females and delayed sexual maturation in males were observed at the highest dose tested. The no-effect dose for ad… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy 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 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 postnatal developmental toxicity in rats is less than the MRHD on a mg/m 2 basis.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of sodium oxybate oral solution in patients with narcolepsy did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects. In controlled trials in another population, 39 (5%) of 874 patients were 65 years or older. Discontinuations of treatment due to adverse reactions were increased in the elderly compared to younger adults (21% vs.
19%). Frequency of headaches was markedly increased in the elderly (39% vs. 19%).
The most common adverse reactions were similar in both age categories. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Human 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.
10.2Signs 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 hypotonia, but tendon reflexes remain intact.
10.3Recommended Treatment of Overdose General symptomatic and supportive care should be instituted immediately, and gastric decontamination may be considered if co-ingestants are suspected. Because emesis may occur in the presence of obtundation, appropriate posture (left lateral recumbent position) and protection of the airway by intubation may be warranted. Although the gag reflex may be absent in deeply comatose patients, even unconscious patients may become combative to intubation, and rapid-sequence induction (without the use of sedative) should be considered.
Vital signs and consciousness should be closely monitored. The bradycardia reported with GHB overdose has been responsive to atropine intravenous administration. No reversal of the central depressant effects of sodium oxybate oral solution can be expected from naloxone or flumazenil administration.
The use of hemodialysis and other forms of extracorporeal drug removal have not been studied in GHB overdose, but have been reported in cases of acidosis associated with GHB ingestions of 125 g or greater; however, due to the rapid metabolism of sodium oxybate, these measures may not be warranted.
10.4Poison Control Center As with the management of all cases of drug overdosage, the possibility of multiple drug ingestion should be considered. The healthcare provider is encouraged to collect urine and blood samples for routine toxicologic screening, and to consult with a regional poison control center (1-800-222-1222) for current treatment recommendations.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Sodium oxybate oral solution is a CNS depressant. The mechanism of action of sodium oxybate oral solution in the treatment of narcolepsy is unknown. Sodium oxybate is the sodium salt of gamma-hydroxybutyrate (GHB), an endogenous compound and metabolite of the neurotransmitter GABA.
It is hypothesized that the therapeutic effects of sodium oxybate oral solution on cataplexy and excessive daytime sleepiness are mediated through GABA B actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.
12.3Pharmacokinetics Pharmacokinetics of GHB are nonlinear and are similar following single or repeat dosing of sodium oxybate oral solution. Absorption Following oral administration of sodium oxybate oral solution, GHB is absorbed rapidly across the clinical dose range, with an absolute bioavailability of about 88%. The average peak plasma concentrations (C max ) following administration of each of the two 2.25 g doses given under fasting conditions 4 hours apart were similar.
The average time to peak plasma concentration (T max ) ranged from 0.5 to 1.25 hours. Following oral administration of sodium oxybate oral solution, the plasma levels of GHB increased more than dose-proportionally, with blood levels increasing 3.7-fold as total daily dose is doubled from 4.5 g to 9 g. Single doses greater than 4.5 g have not been studied.
Effect of Food Administration of sodium oxybate oral solution immediately after a high-fat meal resulted in delayed absorption (average T max increased from 0.75 hr to 2 hr) and a reduction in C max of GHB by a mean of 59% and of systemic exposure (AUC) by 37%. Distribution GHB is a hydrophilic compound with an apparent volume of distribution averaging 190 mL/kg to 384 mL/kg. At GHB concentrations ranging from 3 mcg/mL to 300 mcg/mL, less than 1% is bound to plasma proteins.
Elimination Metabolism Animal studies indicate that metabolism is the major elimination pathway for GHB, producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by beta-oxidation. The primary pathway involves a cytosolic NADP+-linked enzyme, GHB dehydrogenase, that catalyzes the conversion of GHB to succinic semialdehyde, which is then biotransformed to succinic acid by the enzyme succinic semialdehyde dehydrogenase. Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water.
A second mitochondrial oxidoreductase enzyme, a transhydrogenase, also catalyzes the conversion to succinic semialdehyde in the presence of α-ketoglutarate. An alternate pathway of biotransformation involves β-oxidation via 3,4-dihydroxybutyrate to carbon dioxide and water. No active metabolites have been identified.
Excretion The clearance of GHB is almost entirely by biotransformation to carbon dioxide, which is then eliminated by expiration. On average, less than 5% of unchanged drug appears in human urine within 6 to 8 hours after dosing. Fecal excretion is negligible.
GHB has an elimination half-life of 0.5 to 1 hour. Specific Populations Geriatric Patients There is limited experience with sodium oxybate oral solution in the elderly. Results from a pharmacokinetic study (n=20) in another studied population indicate that the pharmacokinetic characteristics of GHB are consistent among younger (age 48 to 64 years) and older (age 65 to 75 years) adults.
Pediatric Patients Pediatric use information is approved for Jazz Pharmaceuticals Inc.’s XYREM (sodium oxybate) Oral Solution. However, due to Jazz Pharmaceuticals Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Male and Female Patients In a study of 18 female and 18 male healthy adult volunteers, no gender differences were detected in the pharmacokinetics of GHB following a single sodium oxybate oral solution oral dose of 4.5 g.
Racial or Ethnic Groups There are insufficient data to evaluate any pharmacokinetic differences… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Sodium oxybate oral solution is a CNS depressant. The mechanism of action of sodium oxybate oral solution in the treatment of narcolepsy is unknown. Sodium oxybate is the sodium salt of gamma-hydroxybutyrate (GHB), an endogenous compound and metabolite of the neurotransmitter GABA.
It is hypothesized that the therapeutic effects of sodium oxybate oral solution on cataplexy and excessive daytime sleepiness are mediated through GABA B actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How 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, and an oral measuring device (plastic syringe). 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 72865-349-18
16.2Storage Keep out of reach of children. Sodium oxybate oral solution should be stored at 20°C to 25°C (68° to 77°F); (see USP Controlled Room Temperature). Dispense in tight containers. Solutions prepared following dilution should be consumed within 24 hours.
16.3Handling 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.
16.1How 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, and an oral measuring device (plastic syringe). 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 72865-349-18
📋 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, 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. structural formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Central Nervous System Depression Inform patients and/or caregivers that sodium oxybate oral solution can cause central nervous system depression, including respiratory depression, hypotension, profound sedation, syncope, and death. Instruct patients to not engage in activities requiring mental alertness or motor coordination, including operating hazardous machinery, for at least 6 hours after taking sodium oxybate oral solution.
Instruct patients and/or their caregivers to inform their healthcare providers of all the medications they take [see Warnings and Precautions (5.1)]. Abuse and Misuse Inform patients and/or caregivers that the active ingredient of sodium oxybate is gamma-hydroxybutyrate (GHB), which is associated with serious adverse reactions with illicit use and abuse [see Warnings and Precautions (5.2)]. Sodium Oxybate REMS Program Sodium oxybate oral solution is available only through a restricted program called the Sodium Oxybate REMS Program [see Warnings and Precautions (5.3)].
Inform the patient and/or caregiver of the following notable requirements: Sodium oxybate oral solution is dispensed only by the certified pharmacy Sodium oxybate oral solution will be dispensed and shipped only to patients enrolled in the Sodium Oxybate REMS Program Sodium oxybate oral solution is available only from the certified pharmacy participating in the program. Therefore, provide patients and/or caregivers with the telephone number and website for information on how to obtain the product. Alcohol or Sedative Hypnotics Advise patients and/or caregivers that alcohol and other sedative hypnotics should not be taken with sodium oxybate oral solution [see Contraindications (4)].
Sedation Inform patients and/or caregivers that the patient is likely to fall asleep quickly after taking sodium oxybate oral solution (often within 5 and usually within 15 minutes), but the time it takes to fall asleep can vary from night to night. The sudden onset of sleep, including in a standing position or while rising from bed, has led to falls complicated by injuries, in some cases requiring hospitalization [see Adverse Reactions (6.2)]. Instruct patients and/or caregivers that the patient should remain in bed following ingestion of the first and second nightly doses.
Instruct patients and/or caregivers that the patient should not take their second nightly dose until 2.5 to 4 hours after the first dose [see Dosage and Administration (2.3)]. Food Effects on Sodium oxybate oral solution Inform patients and/or caregivers that the first nightly dose should be taken at least 2 hours after eating. Respiratory Depression and Sleep-Disordered Breathing Inform patients that sodium oxybate oral solution may impair respiratory drive, especially in patients with compromised respiratory function, and may cause apnea [see Warnings and Precautions (5.4)].
Depression and Suicidality Instruct patients and/or caregivers to contact a healthcare provider immediately if the patient develops depressed mood, markedly diminished interest or pleasure in usual activities, significant change in weight and/or appetite, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or suicidal ideation [see Warnings and Precautions (5.5)]. Other Behavioral or Psychiatric Adverse Reactions Inform patients and/or caregivers that sodium oxybate oral solution can cause behavioral or psychiatric adverse reactions, including confusion, anxiety, and psychosis.
Instruct them to notify their healthcare provider if any of these types of symptoms occur [see Warnings and Precautions (5.6)]. Sleepwalking Instruct patients and/or caregivers that sodium oxybate oral solution has been associated with sleepwalking and other behaviors during sleep, and to contact their hea… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Sodium oxybate (SO dee um OX i bate) oral solution, CIII Read this Medication Guide carefully before you start taking sodium oxybate oral solution and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.
What is the most important information I should know about sodium oxybate oral solution? Sodium oxybate oral solution is a central nervous system (CNS) depressant. Taking sodium oxybate oral solution with other CNS depressants such as medicines used to make you fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol, or street drugs, may cause serious medical problems, including: trouble breathing (respiratory depression) low blood pressure (hypotension) changes in alertness (drowsiness) fainting (syncope) death Ask your doctor if you are not sure if you are taking a medicine listed above.
Sodium oxybate oral solution is a federal controlled substance (CIII). The active ingredient of sodium oxybate oral solution is a form of gamma-hydroxybutyrate (GHB) that is also a federal controlled substance (CI). Abuse of illegal GHB, either alone or with other CNS depressants may cause serious medical problems, including: seizure trouble breathing (respiratory depression) changes in alertness (drowsiness) coma death Call your doctor right away if you have any of these serious side effects.
Anyone who takes sodium oxybate oral solution should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery, or flying an airplane, for at least 6 hours after taking sodium oxybate oral solution. Those activities should not be done until you know how sodium oxybate oral solution affects you. Keep sodium oxybate oral solution in a safe place to prevent abuse and misuse.
Selling or giving away sodium oxybate oral solution may harm others, and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs. Because of the risk of CNS depression, abuse, and misuse, sodium oxybate oral solution is available only by prescription, and filled through the certified pharmacy in the Sodium Oxybate REMS Program.
You must be enrolled in the Sodium Oxybate REMS Program to receive sodium oxybate oral solution. For information on how to receive sodium oxybate oral solution visit www.SOXREMSProgram.com. Before you receive sodium oxybate oral solution, your doctor or pharmacist will make sure that you understand how to take sodium oxybate oral solution safely and effectively.
If you have any questions about sodium oxybate oral solution, ask your doctor or call the Sodium Oxybate REMS Program at 1-833-769-7367 (1-833-SOX-REMS). What is sodium oxybate oral solution? Sodium oxybate oral solution is a prescription medicine used to treat the following symptoms in people with narcolepsy: sudden onset of weak or paralyzed muscles (cataplexy), or excessive daytime sleepiness (EDS) It is not known if sodium oxybate oral solution is safe and effective in children less than 7 years of age.
Do not take sodium oxybate oral solution if you: takes other sleep medicines or sedatives (medicines that cause sleepiness) drinks alcohol has a rare problem called succinic semialdehyde dehydrogenase deficiency Before taking sodium oxybate oral solution, tell your doctor about all medical conditions, including if you : have a history of drug abuse. have short periods of not breathing while sleeping (sleep apnea) has trouble breathing or has lung problems. You may have a higher chance of having serious breathing problems when taking sodium oxybate oral solution. have or had depression or has tried to harm yourself or themselves.
You should be watched carefully for new symptoms of depression. has or had behavior or… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Pharmacokinetics of GHB are nonlinear and are similar following single or repeat dosing of sodium oxybate oral solution. Absorption Following oral administration of sodium oxybate oral solution, GHB is absorbed rapidly across the clinical dose range, with an absolute bioavailability of about 88%. The average peak plasma concentrations (C max ) following administration of each of the two 2.25 g doses given under fasting conditions 4 hours apart were similar.
The average time to peak plasma concentration (T max ) ranged from 0.5 to 1.25 hours. Following oral administration of sodium oxybate oral solution, the plasma levels of GHB increased more than dose-proportionally, with blood levels increasing 3.7-fold as total daily dose is doubled from 4.5 g to 9 g. Single doses greater than 4.5 g have not been studied.
Effect of Food Administration of sodium oxybate oral solution immediately after a high-fat meal resulted in delayed absorption (average T max increased from 0.75 hr to 2 hr) and a reduction in C max of GHB by a mean of 59% and of systemic exposure (AUC) by 37%. Distribution GHB is a hydrophilic compound with an apparent volume of distribution averaging 190 mL/kg to 384 mL/kg. At GHB concentrations ranging from 3 mcg/mL to 300 mcg/mL, less than 1% is bound to plasma proteins.
Elimination Metabolism Animal studies indicate that metabolism is the major elimination pathway for GHB, producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by beta-oxidation. The primary pathway involves a cytosolic NADP+-linked enzyme, GHB dehydrogenase, that catalyzes the conversion of GHB to succinic semialdehyde, which is then biotransformed to succinic acid by the enzyme succinic semialdehyde dehydrogenase. Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water.
A second mitochondrial oxidoreductase enzyme, a transhydrogenase, also catalyzes the conversion to succinic semialdehyde in the presence of α-ketoglutarate. An alternate pathway of biotransformation involves β-oxidation via 3,4-dihydroxybutyrate to carbon dioxide and water. No active metabolites have been identified.
Excretion The clearance of GHB is almost entirely by biotransformation to carbon dioxide, which is then eliminated by expiration. On average, less than 5% of unchanged drug appears in human urine within 6 to 8 hours after dosing. Fecal excretion is negligible.
GHB has an elimination half-life of 0.5 to 1 hour. Specific Populations Geriatric Patients There is limited experience with sodium oxybate oral solution in the elderly. Results from a pharmacokinetic study (n=20) in another studied population indicate that the pharmacokinetic characteristics of GHB are consistent among younger (age 48 to 64 years) and older (age 65 to 75 years) adults.
Pediatric Patients Pediatric use information is approved for Jazz Pharmaceuticals Inc.’s XYREM (sodium oxybate) Oral Solution. However, due to Jazz Pharmaceuticals Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Male and Female Patients In a study of 18 female and 18 male healthy adult volunteers, no gender differences were detected in the pharmacokinetics of GHB following a single sodium oxybate oral solution oral dose of 4.5 g.
Racial or Ethnic Groups There are insufficient data to evaluate any pharmacokinetic differences among races. Patients with Renal Impairment No pharmacokinetic study in patients with renal impairment has been conducted. Patients with Hepatic Impairment The pharmacokinetics of GHB in 16 cirrhotic patients, half without ascites (Child’s Class A) and half with ascites (Child’s Class C), were compared to the kinetics in 8 subjects with normal hepatic function after a single sodium oxybate oral solution oral dose of 25 mg/kg.
AUC values were double in the cirrhotic patients, with apparent oral clearance reduced from 9.1 mL/min/kg in healthy adults to 4.5 and 4.1 mL/min/k… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14 CLINICAL STUDIES The efficacy of sodium oxybate oral solution for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy has been established in the following adequate and well-controlled trials: Cataplexy in adult narcolepsy in Trials N1 and N2 [see Clinical Studies ( 14.1 )] Excessive Daytime Sleepiness (EDS) in adult narcolepsy in Trials N3 and N4 [see Clinical Studies ( 14.2 )] Pediatric use information is approved for Jazz Pharmaceuticals Inc.’s XYREM (sodium oxybate) Oral Solution.
However, due to Jazz Pharmaceuticals Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
14.1Cataplexy in Adult Narcolepsy The effectiveness of sodium oxybate oral solution in the treatment of cataplexy was established in two randomized, double-blind, placebo-controlled, multicenter, parallel-group trials (Trials N1 and N2) in patients with narcolepsy (see Table 5). In Trials N1 and N2, 85% and 80% of patients, respectively, were also being treated with CNS stimulants. The high percentages of concomitant stimulant use make it impossible to assess the efficacy and safety of sodium oxybate oral solution independent of stimulant use.
In each trial, the treatment period was 4 weeks and the total nightly sodium oxybate oral solution doses ranged from 3 g to 9 g, with the total nightly dose administered as two equal doses. The first dose each night was taken at bedtime and the second dose was taken 2.5 to 4 hours later. There were no restrictions on the time between food consumption and dosing.
Trial N1 enrolled 136 narcoleptic patients with moderate to severe cataplexy (median of 21 cataplexy attacks per week) at baseline. Prior to randomization, medications with possible effects on cataplexy were withdrawn, but stimulants were continued at stable doses. Patients were randomized to receive placebo, sodium oxybate oral solution 3 g per night, sodium oxybate oral solution 6 g per night, or sodium oxybate oral solution 9 g per night.
Trial N2 was a randomized-withdrawal trial with 55 narcoleptic patients who had been taking open-label sodium oxybate oral solution for 7 to 44 months prior to study entry. To be included, patients were required to have a history of at least 5 cataplexy attacks per week prior to any treatment for cataplexy. Patients were randomized to continued treatment with sodium oxybate oral solution at their stable dose (ranging from 3 g to 9 g per night) or to placebo for 2 weeks.
Trial N2 was designed specifically to evaluate the continued efficacy of sodium oxybate after long-term use. The primary efficacy measure in Trials N1 and N2 was the frequency of cataplexy attacks. Table 5 Median Number of Cataplexy Attacks in Trials N1 and N2 Trial/Dosage Group Baseline Median Change from Baseline Comparison to Placebo (p‑value) Trial N1 (Prospective, Randomized, Parallel Group Trial) (median attacks/week) Placebo (n=33) 20.5 -4 – Sodium oxybate oral solution 6 g per night (n=31) 23.0 -10 0.0451 Sodium oxybate oral solution 9 g per night (n=33) 23.5 -16 0.0016 Trial N2 (Randomized-Withdrawal Trial) (median attacks/2 weeks) Placebo (n=29) 4.0 21 – Sodium oxybate oral solution (n=26) 1.9 0 <0.001 In Trial N1, both the 6 g and 9 g per night sodium oxybate oral solution doses resulted in statistically significant reductions in the frequency of cataplexy attacks.
The 3 g per night dose had little effect. In Trial N2, patients randomized to placebo after discontinuing long-term open-label sodium oxybate oral solution therapy experienced a significant increase in cataplexy attacks (p<0.001), providing evidence of long-term efficacy of sodium oxybate oral solution. In Trial N2, the response was numerically similar for patients treated with doses of 6 g to 9 g per night, but there was no effect seen in patients treated with doses less than 6 g per night, suggesting little effect at these doses.
14.2Excessive Daytime Sleepiness in Adult Narcolepsy The effe… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Sodium oxybate oral solution is a Schedule III controlled substance under the Federal Controlled Substances Act. Non-medical use of sodium oxybate oral solution could lead to penalties assessed under the higher Schedule I controls.
9.2Abuse Sodium oxybate oral solution, the sodium salt of GHB, produces dose-dependent central nervous system effects, including hypnotic and positive subjective reinforcing effects. The onset of effect is rapid, enhancing its potential for abuse or misuse. Drug abuse is the intentional non-therapeutic use of a drug product or substance, even once, for its desirable psychological or physiological effects.
Misuse is the intentional use, for therapeutic purposes of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug misuse and abuse may occur with or without progression to addiction. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
The rapid onset of sedation, coupled with the amnestic features of GHB, particularly when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user (e.g., assault victim). Illicit GHB is abused in social settings primarily by young adults. Some of the doses estimated to be abused are in a similar dosage range to that used for treatment of patients with cataplexy.
GHB has some commonalities with ethanol over a limited dose range, and some cross tolerance with ethanol has been reported as well. Cases of severe dependence and craving for GHB have been reported when the drug is taken around the clock. Patterns of abuse indicative of dependence include: 1) the use of increasingly large doses, 2) increased frequency of use, and 3) continued use despite adverse consequences.
Because illicit use and abuse of GHB have been reported, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of GHB (e.g., increase in size or frequency of dosing, drug-seeking behavior, feigned cataplexy). Dispose of sodium oxybate oral solution according to state and federal regulations. It is safe to dispose of sodium oxybate oral solution down the sanitary sewer.
9.3Dependence Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. There have been case reports of withdrawal, ranging from mild to severe, following discontinuation of illicit use of GHB at frequent repeated doses (18 g to 250 g per day) in excess of the recommended dosage range. Signs and symptoms of GHB withdrawal following abrupt discontinuation included insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and, particularly in the case of severe withdrawal, visual hallucinations, agitation, and delirium.
These symptoms generally abated in 3 to 14 days. In cases of severe withdrawal, hospitalization may be required. The discontinuation effects of sodium oxybate oral solution have not been systematically evaluated in controlled clinical trials.
In the clinical trial experience with sodium oxybate oral solution in narcolepsy/cataplexy patients at recommended doses, two patients reported anxiety and one reported insomnia following abrupt discontinuation at the termination of the clinical trial; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time. Tolerance T… [Excerpted — this section continues on DailyMed.]
🔒 Controlled Substance ▾
9.1Controlled Substance Sodium oxybate oral solution is a Schedule III controlled substance under the Federal Controlled Substances Act. Non-medical use of sodium oxybate oral solution could lead to penalties assessed under the higher Schedule I controls.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Administration of sodium oxybate to rats at oral doses of up to 1,000 mg/kg/day for 83 (males) or 104 (females) weeks resulted in no increase in tumors. Plasma exposure (AUC) at the highest dose tested was 2 times that in humans at the maximum recommended human dose (MRHD) of 9 g per night. The results of 2-year carcinogenicity studies in mouse and rat with gamma-butyrolactone, a compound that is metabolized to sodium oxybate in vivo , showed no clear evidence of carcinogenic activity.
The plasma AUCs of sodium oxybate achieved at the highest doses tested in these studies were less than that in humans at the MRHD. Mutagenesis Sodium oxybate was negative in the in vitro bacterial gene mutation assay, an in vitro chromosomal aberration assay in mammalian cells, and in an in vivo rat micronucleus assay. Impairment of Fertility Oral administration of sodium oxybate (150, 350, or 1,000 mg/kg/day) to male and female rats prior to and throughout mating and continuing in females through early gestation resulted in no adverse effects on fertility.
The highest dose tested is approximately equal to the MRHD on a mg/m 2 basis.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Administration of sodium oxybate to rats at oral doses of up to 1,000 mg/kg/day for 83 (males) or 104 (females) weeks resulted in no increase in tumors. Plasma exposure (AUC) at the highest dose tested was 2 times that in humans at the maximum recommended human dose (MRHD) of 9 g per night. The results of 2-year carcinogenicity studies in mouse and rat with gamma-butyrolactone, a compound that is metabolized to sodium oxybate in vivo , showed no clear evidence of carcinogenic activity.
The plasma AUCs of sodium oxybate achieved at the highest doses tested in these studies were less than that in humans at the MRHD. Mutagenesis Sodium oxybate was negative in the in vitro bacterial gene mutation assay, an in vitro chromosomal aberration assay in mammalian cells, and in an in vivo rat micronucleus assay. Impairment of Fertility Oral administration of sodium oxybate (150, 350, or 1,000 mg/kg/day) to male and female rats prior to and throughout mating and continuing in females through early gestation resulted in no adverse effects on fertility.
The highest dose tested is approximately equal to the MRHD on a mg/m 2 basis.
📖 Instructions for Use ▾
Instructions for Use Sodium Oxybate (SO dee um OX i bate) Oral Solution, CIII Read this Instructions for Use carefully before you start taking sodium oxybate oral solution and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.
Important Information: You will need to split your prescribed sodium oxybate oral solution dose into 2 separate pharmacy containers for mixing. You will need to mix sodium oxybate oral solution with water before you take the dose. Safely store the prepared sodium oxybate oral solution doses and take within 24 hours after mixing.
If the prepared dose was not taken within this time, throw the mixture away. See “Throwing away (disposing of) sodium oxybate oral solution” section below for instructions about how to safely throw away sodium oxybate oral solution. Both sodium oxybate oral solution doses should be taken while in bed.
The pharmacy containers may be rinsed out with water and emptied into the sink drain. Supplies you will need for mixing and taking sodium oxybate oral solution. See Figure A: Bottle of sodium oxybate oral solution medicine Dosing syringe for measuring and dispensing the sodium oxybate oral solution dose Measuring cup that is able to measure about ¼ cup of water (not provided with the sodium oxybate oral solution shipment) 2 empty pharmacy containers with child-resistant caps for mixing, storing, and taking the sodium oxybate oral solution doses Alarm clock (not pictured which may be included in the first shipment) Medication Guide Step 1: Setup Take the sodium oxybate oral solution bottle, syringe, and pharmacy containers out of the shipping box.
Take the syringe out of the plastic wrapper. Use only the syringe provided with the sodium oxybate oral solution prescription. Fill a measuring cup (not provided) with about ¼ cup of water available for mixing your dose.
Make sure the pharmacy containers are empty. Open both pharmacy containers by holding the tab under the cap and turning counterclockwise (to the left). See Figure B.
Remove the tamper evident band by pulling at the perforations and then remove the bottle cap from the sodium oxybate oral solution bottle by pushing down while turning the cap counterclockwise. See Figure C. Step 2.
Prepare the first sodium oxybate oral solution dose (prepare before bedtime) Place the sodium oxybate oral solution bottle on a hard, flat surface and grip the bottle with one hand and firmly press the syringe into the center opening of the bottle with the other hand. See Figure D. Figure D Pull back on the plunger until the medicine flows into the syringe and the liquid level is lined up with the marking on the syringe that matches your dose.
See Figure E . Figure E Note: The sodium oxybate oral solution medicine will not flow into the syringe unless you keep the bottle upright. Figure F shows an example of drawing up a sodium oxybate oral solution dose of 2.25 g.
Figure G shows an example if an air space forms when drawing up the dose. Figure F Figure G Note: If an air space forms between the plunger and the liquid when drawing up the medicine, line up the liquid level with the marking on the syringe that matches your dose. See Figure G above.
After you draw up the first divided sodium oxybate oral solution dose, remove the syringe from the opening of the sodium oxybate oral solution bottle. Empty all of the medicine from the syringe into one of the provided empty pharmacy containers by pushing down on the plunger until it stops. See Figure H.
Figure H Using a measuring cup, pour about ¼ cup of water into the pharmacy container. Be careful to add only water to the pharmacy container and not more sodium oxybate oral solution. All shipped bottles of sodium oxybate oral solution contain the concentrated medicine.
Water for mixing the medicine is not provided in the shipment. After mixing the medicine and water in the provided pharmacy… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PACKAGE/LABEL DISPLAY PANEL Bottle label Carton label
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About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
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| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
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