(SOW dee um ox i BATE)
- Gamma Hydroxybutyric Acid
- Sodium 4-Hydroxybutyrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Xyrem: 500 mg/mL (180 mL)
Brand Names: U.S.
- Central Nervous System Depressant
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).
190 to 384 mL/kg
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
Primarily pulmonary (as carbon dioxide); urine (<5% as unchanged drug); feces (negligible)
Time to Peak
30 to 75 minutes
30 to 60 minutes
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 and excessive daytime sleepiness in patients with narcolepsy
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
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). Titrate 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; usual effective dosage range: 6 to 9 g per night (maximum dose: 9 g per night).
Dosage adjustment for concomitant therapy: Patients stabilized on sodium oxybate should have dose reduced by at least 20% with the addition of divalproex sodium. The sodium oxybate starting dose should be reduced for patients already taking divalproex sodium. Adjust dose as necessary.
Refer to adult dosing. Use with caution; initiate at lower dosage range. Limited studies available in patients >65 years.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosing: Hepatic Impairment
Initial: ~1.13 g at bedtime after the patient is in bed and ~1.13 g 2.5 to 4 hours later (2.25 g per night)
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.
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 5-15 minutes; patients may take up to 2 hours to fall asleep (rare).
Contains a high sodium content; limit dietary intake of sodium.
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).
Alcohol (Ethyl): May enhance the CNS depressant effect of Sodium Oxybate. Avoid combination
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Benzodiazepines: May enhance the CNS depressant effect of Sodium Oxybate. Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
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: Sodium Oxybate may enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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 (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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
Hypnotics (Nonbenzodiazepine): May enhance the CNS depressant effect of Sodium Oxybate. Avoid combination
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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
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: May enhance the CNS depressant effect of Sodium Oxybate. 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
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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
Tetrahydrocannabinol: 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 Sodium Oxybate. Management: Consider a sodium oxybate dose reduction of at least 20% if combined with valproic acid. Consider therapy modification
Central nervous system: Confusion (3% to 17%; dose-related), dizziness (9% to 15%)
Gastrointestinal: Nausea (8% to 20%; dose-related), vomiting (2% to 11%; dose-related)
1% to 10%:
Cardiovascular: Peripheral edema (≤3%)
Central nervous system: Drowsiness (8%), depression (3% to 7%), somnambulism (3% to 6%; dose-related), anxiety (2% to 6%), disturbance in attention (1% to 4%; dose-related), intoxicated feeling (3%; dose-related), irritability (3%; dose-related), pain (3%), sleep paralysis (3%), disorientation (2% to 3%; dose-related), paresthesia (2% to to 3%; dose-related), severe central nervous system depression (2%)
Dermatologic: Hyperhidrosis (1% to 3%)
Gastrointestinal: Diarrhea (3% to 4%), upper abdominal pain (3%)
Genitourinary: Urinary incontinence (3% to 7%; dose-related)
Neuromuscular & skeletal: Tremor (2% to 5%), limb pain (3%), cataplexy (2%)
Frequency not defined:
Central nervous system: Central nervous system depression
Respiratory: Respiratory depression
<1% (Limited to important or life-threatening): Aggressive behavior, agitation, arthralgia, blurred vision, decreased appetite, falling, fluid retention, hallucination, hangover effect, headache, hypersensitivity reaction, hypertension, memory impairment, nocturia, panic attack, paranoia, psychosis, suicidal ideation, weight loss
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 patients. Almost all 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.
• 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, postmenopausal (not on hormone replacement therapy), or narcoleptic.
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.
• 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.
• 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 Xyrem REMS Program and dispensed to the patient only by the central pharmacy that is speciality certified (1-866-997-3688 or www.xyremrems.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.
Signs and symptoms of depression or suicidality; emergence of anxiety, confusion, thought disorders, or behavior abnormalities; drug abuse, misuse, and addiction
Pregnancy Risk Factor
Adverse effects have been reported with maternal use. The injection formulation, when used as an anesthetic during labor and delivery, was shown to cross the placenta in concentrations ≤25% of maternal levels; a slight decrease in Apgar scores due to sleepiness in the neonate was observed. Sodium oxybate was not detected in infant blood 30 minutes after delivery.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience dizziness, fatigue, nausea, vomiting, bedwetting, tremors, or diarrhea. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), hallucinations, confusion, behavioral changes, sleepwalking, difficulty breathing, slow breathing, or shallow breathing (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
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- Drug class: miscellaneous anxiolytics, sedatives and hypnotics
Other brands: Xyrem