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Sodium Oxybate

Medically reviewed by Drugs.com. Last updated on Aug 24, 2020.

Pronunciation

(SOW dee um ox i BATE)

Index Terms

  • 4-Hydroxybutyrate
  • Gamma Hydroxybutyric Acid
  • GHB
  • Oxybate
  • Sodium 4-Hydroxybutyrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Xyrem: 500 mg/mL (180 mL)

Brand Names: U.S.

  • Xyrem

Pharmacologic Category

  • Central Nervous System Depressant

Pharmacology

Sodium oxybate is derived from gamma aminobutyric acid (GABA) and acts as an inhibitory chemical transmitter in the brain. May function through specific receptors for gamma hydroxybutyrate (GHB) and GABA (B).

Absorption

Rapid

Distribution

190 to 384 mL/kg

Metabolism

Primarily via the Krebs cycle to form water and carbon dioxide; secondarily via beta oxidation; significant first-pass effect; no active metabolites; metabolic pathways are saturable

Excretion

Primarily pulmonary (as carbon dioxide); urine (<5% as unchanged drug); feces (negligible)

Time to Peak

30 to 75 minutes

Half-Life Elimination

30 to 60 minutes

Protein Binding

<1%

Special Populations: Hepatic Function Impairment

AUC is doubled, elimination half-life is longer, and oral clearance is reduced in cirrhotic patients (Child-Pugh class A and C).

Use: Labeled Indications

Narcolepsy: Treatment of cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy

Contraindications

Concomitant use with ethanol or sedative-hypnotic agents; succinic semialdehyde dehydrogenase deficiency

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to sodium oxybate or any component of the formulation

Dosing: Adult

Narcolepsy (excessive daytime sleepiness/cataplexy): Oral: Initial: 2.25 g at bedtime after the patient is in bed, and 2.25 g 2.5 to 4 hours later (4.5 g per night). May increase dose by 1.5 g per night (0.75 g at bedtime and 0.75 g 2.5 to 4 hours later) in weekly intervals based on efficacy and tolerability; usual effective dosage range: 6 to 9 g per night (maximum dose: 9 g per night).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Missed dose: If the second dose is missed, skip that dose and resume therapy the next night; do not take both doses at the same time.

Dosing: Geriatric

Refer to adult dosing. Use with caution; initiate at lower dosage range. Limited studies available in patients ≥65 years.

Dosing: Pediatric

Narcolepsy (excessive daytime sleepiness/cataplexy): Note: Nightly, 2 doses are administered; some patients may require unequal doses to achieve optimal response. Dosing is present in mg/kg and grams; use precaution.

Children ≥7 years and Adolescents:

<20 kg: Oral: Limited data available: Initial: 60 to 90 mg/kg/night (total dose) in 2 divided doses; the first dose administered at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer the second dose; titrate every 1 to 2 weeks until efficacy or development of intolerable side effects. Reported maximum daily dose: 180 mg/kg/night (Aran 2010; Moresco 2018).

20 to <30 kg: Oral: Initial: ≤1 g at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer second dose of ≤1 g. After 1 week, titrate dose based on efficacy and tolerability at weekly intervals; increase dose in ≤0.5 g/dose (≤1 g/night) increments per week; maximum single dose: 3 g/dose; maximum daily dose: 6 g/night.

30 to <45 kg: Oral: Initial: ≤1.5 g at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer second dose of ≤1.5 g. After 1 week, titrate dose based on efficacy and tolerability at weekly intervals; increase dose in ≤0.5 g/dose (≤1 g/night) increments per week; maximum single dose: 3.75 g/dose; maximum daily dose: 7.5 g/ night.

≥45 kg: Oral: Initial: ≤2.25 g at bedtime after the patient is in bed, then 2.5 to 4 hours later, administer second dose of ≤2.25 g . After 1 week, titrate dose based on efficacy and tolerability at weekly intervals; increase dose in ≤0.75 g/dose (1.5 g/night) increments per week; maximum single dose: 4.5 g/dose; maximum daily dose: 9 g/night.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Prepare both doses prior to bedtime and place safely near bed, out of reach of pets and children. Each dose should be diluted with 60 mL of water in the provided child-resistant dosing cups. Once diluted, solutions should be used within 24 hours.

Administration

Oral: Administer on an empty stomach; separate last meal (or food) and first dose by ≥2 hours; try to take at similar time each day. Doses should be administered while in bed; patient should lie down immediately after dose and should remain in bed. Both doses should be prepared prior to bedtime. The first dose is taken at bedtime and the second dose is taken 2.5 to 4 hours later; an alarm clock may need to be set for the second dose. Patients typically fall asleep within 5 to 15 minutes; patients may take up to 2 hours to fall asleep (rare).

Dietary Considerations

Contains a high sodium content; limit dietary intake of sodium.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86 °F). Store in the original bottle and in a safe and secure place (may need to be locked up).

Drug Interactions

Alcohol (Ethyl): May enhance the CNS depressant effect of Oxybate Salt Products. Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Benzodiazepines: May enhance the CNS depressant effect of Oxybate Salt Products. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interupt oxybate salt treatment during short-term opioid use. Exceptions: Valproic Acid and Derivatives. Consider therapy modification

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Hypnotics (Nonbenzodiazepine): May enhance the CNS depressant effect of Oxybate Salt Products. Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interupt oxybate salt treatment during short-term opioid use. Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Rilmenidine: Oxybate Salt Products may enhance the CNS depressant effect of Rilmenidine. Avoid combination

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Valproate Products: May increase the serum concentration of Oxybate Salt Products. Management: Decrease the dose of the oxybate salt product by at least 20% when initiating therapy with valproate products. When initiating oxybate salt products in patients taking valproate products, use a lower starting dose of the oxybate salt. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Confusion (adults: 3% to 17%), headache (≤16%), dizziness (6% to 15%)

Endocrine & metabolic: Weight loss (≤12%)

Gastrointestinal: Nausea (8% to 20%), vomiting (2% to 16%)

Genitourinary: Urinary incontinence (children and adolescents: 18%; adults: 3% to 7%)

1% to 10%:

Cardiovascular: Peripheral edema (adults: 3%)

Central nervous system: Drowsiness (adults: 8%), depression (adults: 3% to 7%), somnambulism (adults: 3% to 6%), anxiety (adults: 2% to 6%), disturbance in attention (adults: 1% to 4%), intoxicated feeling (adults: 3%), irritability (adults: 3%), pain (adults: 3%), sleep paralysis (adults: 3%), disorientation (adults: 2% to 3%), paresthesia (adults: 2% to 3%), severe central nervous system depression (adults: 2%)

Dermatologic: Hyperhidrosis (adults: 1% to 3%)

Gastrointestinal: Decreased appetite (≤8%), diarrhea (adults: 3% to 4%), upper abdominal pain (adults: 3%)

Neuromuscular & skeletal: Tremor (adults: 2% to 5%), limb pain (adults: 3%), cataplexy (adults: 2%)

Frequency not defined:

Central nervous system: Central nervous system depression, obtundation, sleep apnea

Hematologic & oncologic: Oxygen desaturation

Respiratory: Respiratory depression

<1%, postmarketing, and/or case reports: Acute psychosis, aggressive behavior, agitation, arthralgia, blurred vision, falling, fluid retention, hallucination, hangover effect, hypersensitivity reaction, hypertension, increased libido, memory impairment, nocturia, panic attack, paranoia, psychosis, suicidal ideation

ALERT: U.S. Boxed Warning

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. Many patients who received sodium oxybate during clinical trials in narcolepsy were receiving CNS stimulants.

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.

Restricted access:

Because of the risks of CNS depression, abuse, and misuse, sodium oxybate is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Xywav and Xyrem REMS.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause anxiety, confusion, psychosis, paranoia, hallucinations, agitation, depression, suicidality and sleepwalking; use caution with in patients with history of depression and/or suicide attempt. Patients should be instructed not to engage in hazardous activities requiring mental alertness for at least 6 hours after taking the second nightly dose of this medication. Concurrent use with other CNS depressants may increase the risk of respiratory depression, hypotension, excessive sedation, syncope, and death. Use is contraindicated with alcohol and sedative hypnotics; concomitant CNS depressant use should generally be avoided; however, if concomitant use is required, dosage adjustments or discontinuation of one or more CNS depressant agent (including sodium oxybate) should be considered. If short-term opioid use is required, consider temporarily discontinuing sodium oxybate.

• Respiratory depression: [US Boxed Warning]: In clinical trials at recommended doses, obtundation and clinically significant respiratory depression occurred in sodium oxybate-treated adult patients. Many of the patients who received sodium oxybate during clinical trials in narcolepsy were receiving CNS stimulants. Use with caution in patients with compromised respiratory function.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure or hypertension; contains significant amounts of sodium. Concomitant use with CNS depressants may increase risk of syncope and hypotension; dosage adjustments should be considered.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment is recommended.

• Renal impairment: Use with caution in patients with renal impairment due to significant amounts of sodium in the product.

• Sleep-related breathing disorders: Sleep-related breathing disorders (eg, sleep apnea) may occur during therapy; may be more common in patients that are obese, male, postmenopausal (not on hormone-replacement therapy), or narcoleptic. In pediatric patients, central sleep apnea and oxygen desaturation has been reported.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Although limited data exists, headache was observed at a higher incidence in older adults ≥65 years of age compared to younger adults. Elderly may also be at increased risk for other CNS effects; use with caution and monitor cognitive/motor function closely.

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Sodium oxybate (the sodium salt of gamma hydroxybutyrate [GHB]) is a CNS depressant controlled substance with abuse potential. Seizures, respiratory depression, decreases in level of consciousness, coma, and death have been reported when GHB, either alone or in combination with other CNS depressants, has been abused. Health care providers should be alert to problems of abuse, misuse, and diversion. Patients should be evaluated for a history of drug abuse and should be monitored for signs of misuse, abuse, and addiction.

• Restricted access: [US Boxed Warning]: Sodium oxybate is available only through a restricted distribution program to prescribers and patients enrolled in the Xywav and Xyrem REMS and dispensed to the patient only by the central pharmacy that is specially certified (1-866-997-3688 or www.xywavxyremrems.com).

• Sodium: Contains high sodium content: Use with caution in patients sensitive to high sodium intake (eg, renal impairment, HF, hypertension).

• Tolerance/withdrawal: Tolerance to sodium oxybate, or withdrawal following its discontinuation, has not been clearly defined in controlled clinical trials, but has been reported at larger doses used for illicit purposes.

Monitoring Parameters

Signs and symptoms of depression or suicidality; emergence of anxiety, confusion, thought disorders, or behavior abnormalities; drug abuse, misuse, and addiction

Pregnancy Considerations

The injection formulation, when used as an anesthetic during labor and delivery, was shown to cross the placenta; a slight decrease in Apgar scores due to sleepiness in the neonate was observed.

Patient Education

What is this drug used for?

• It is used to treat sudden loss of muscle tone (cataplexy) in patients with narcolepsy.

• It is used to treat a lot of sleepiness during the day in patients with narcolepsy.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Nausea

• Vomiting

• Bedwetting

• Tremors

• Headache (children)

• Weight loss (children)

• Lack of appetite (children)

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.

• Sensing things that seem real but are not

• Confusion

• Behavioral changes

• Sleepwalking

• Sleep apnea

• Severe dizziness

• Passing out

• Trouble breathing

• Slow breathing

• Shallow breathing

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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