Trade Names:Xyrem- Solution, oral 500 mg/mL
CNS depressant with anticatapletic activity in patients with narcolepsy. Precise mechanism of action is unknown.
Rapidly but incompletely absorbed following oral administration. Absolute bioavailability is approximately 25%. T max ranges from 0.5 to 1.25 h. Administration following high-fat meal delays absorption (T max averages 2 h) and reduces C max an average of 58% and AUC 37%. Pharmacokinetics are nonlinear with blood levels increasing 3.7-fold as dose is doubled from 4.5 to 9 g.
Vd is 190 to 384 mL/kg. Less than 1% bound to plasma proteins.
Undergoes significant hepatic first-pass metabolism and is metabolized to carbon dioxide and water via Krebs cycle and secondarily by beta-oxidation.
Elimination t ½ is 0.5 to 1 h. Cl almost entirely by biotransformation to carbon dioxide, which is then eliminated by expiration. Less than 5% of unchanged drug appears in urine within 6 to 8 h after administration. Fecal excretion is minimal.
Treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.
Fibromyalgia pain and fatigue.
Treatment with sedative hypnotic agents; succinic semialdehyde dehydrogenase deficiency; hypersensitivity to any component of the product.
PO Taken in 2 equal doses, the first at bedtime while in bed and again 2.5 to 4 h later while sitting in bed. Initial dose: 4.5 g/night divided into 2 equal doses of 2.25 g. Dose may be increased in 0.75 g/dose increments, no more often than every 2 wk, to a max of 9 g/night.
Measure prescribed dose using supplied dosing syringe; dilute each dose with 2 oz of water prior to bedtime.Hepatic Function ImpairmentAdults
PO Reduce starting dose 50%; titrate dose increments to effect while closely monitoring potential adverse reactions.
Store at 59° to 86°F. Use diluted solutions within 24 h to minimize bacterial growth and contamination.
Possible additive or potentiated CNS depressant effects.
None well documented.
Increased BP (6%).
Dizziness, headache (37%); sleep paralysis, somnolence (14%); disorientation, disturbance in attention, feeling drunk (9%); confusion, depression, hypesthesia, lethargy, nightmare, sleepwalking (6%); abnormal dreams, asthenia, balance disorder, fatigue, impaired memory, insomnia, malaise, nervousness, pyrexia, sleep disorder (at least 1%).
Hyperhidrosis (6%); pruritus (at least 1%).
Blurred vision, nasopharyngitis, tinnitus (6%); ear pain, nasal congestion, vertigo (at least 1%).
Nausea (40%); vomiting (23%); upper abdominal pain (11%); diarrhea, dyspepsia (9%); viral gastroenteritis (6%); anorexia, constipation, toothache (at least 1%).
Enuresis (17%); UTI (at least 1%).
Decreased weight (at least 1%).
Cataplexy (9%); back pain, muscular weakness (6%); arthralgia, myalgia, neck pain (at least 1%).
Pharyngolaryngeal pain (9%); upper respiratory tract infection (6%); bronchitis, cough, dyspnea, sinus congestion, sinusitis (at least 1%).
Pain, postprocedural pain (6%); activated pain trauma, chest pain, contusion, fall, influenza, influenza-like symptoms (at least 1%).
Sodium oxybate is a CNS depressant with abuse potential. Do not use with alcohol or other CNS depressants.
Sodium oxybate is gamma hydroxybutyrate (GHB), a drug associated with important CNS adverse reactions, including seizures, respiratory depression, and profound decreases in level of consciousness, with instances of coma and death. Even at recommended doses, confusion, depression, and other neuropsychiatric reactions have occurred. Reports of respiratory depression occurred in clinical trials. Sodium oxybate is available only through restricted distribution, the Xyrem Success Program, which is intended to educate health care providers and patients and to prevent diversion.
The Xyrem Success Program includes provisions for detailed surveillance of patients. Patients are to be seen every 3 mo, and health care providers are expected to report all serious adverse reactions to the manufacturer.
Monitor for symptoms of abuse, dependence, and tolerance. Carefully monitor patients with history of a depressive illness and/or suicide attempt for emergence of depressive symptoms. Monitor patient's response to therapy.
Category B .
Safety and efficacy not established in patients younger than 16 yr of age.
Closely monitor for impaired motor and/or cognitive function.
Patients with compromised liver function have an increased elimination t ½ and systemic exposure to sodium oxybate.
Because of the rapid onset of CNS-depressant effects, sodium oxybate should only be ingested at bedtime and while in bed. Patients must not engage in hazardous occupations or activities requiring complete mental alertness or coordination for at least 6 h after taking sodium oxybate. Extreme care should be used while engaging in hazardous occupations or activities on days following initial use of sodium oxybate until carryover effects are determined.
Monitor patients for neuropsychiatric events (depression, confusion, psychosis, paranoia, hallucinations, agitation). Emergence of depressive symptoms, thought disorders, and/or behavior abnormalities requires careful and immediate evaluation.
Illicit use and abuse and dependence have been reported. Abrupt discontinuation in this setting has resulted in an abstinence syndrome consisting of insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, and tachycardia. An abstinence syndrome has not been reported in clinical trials using therapeutic doses of sodium oxybate.
Positive antinuclear antibody tests have been reported.
May cause fecal and/or urinary incontinence. If fecal or urinary incontinence occurs, consider methods to rule out underlying etiologies (eg, worsening sleep apnea, nocturnal seizures).
Because sodium oxybate can impair respiratory function, use caution in patients with compromised respiratory function, including sleep apnea. Monitor such patients for respiratory depressant effects.
Confused behavior at night, at times associated with wandering, can occur and has been associated with injury and potential injury. Fully evaluate episodes of sleepwalking and consider appropriate interventions.
Daily sodium intake ranges from 0.5 g (for sodium oxybate 3 g dose) to 1.6 g (for sodium oxybate 9 g dose). Consider this in patients with heart failure, hypertension, or compromised renal function.
There have been case reports of tolerance developing after illicit use of sodium oxybate at doses in excess of the recommended dosage regimen. Cross-tolerance with alcohol may occur.
Brief periods of apnea, incontinence of urine and feces, respiratory depression, unresponsiveness. Other reports are confounded by multiple drug ingestion.
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