Sodium Oxybate

Pronunciation: SO-dee-um OX-i-bate
Class: CNS agent

Trade Names

Xyrem
- Solution, oral 500 mg/mL

Pharmacology

CNS depressant with anticatapletic activity in patients with narcolepsy. Precise mechanism of action is unknown.

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Pharmacokinetics

Absorption

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.

Distribution

Vd is 190 to 384 mL/kg. Less than 1% bound to plasma proteins.

Metabolism

Undergoes significant hepatic first-pass metabolism and is metabolized to carbon dioxide and water via Krebs cycle and secondarily by beta-oxidation.

Elimination

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.

Indications and Usage

Treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.

Unlabeled Uses

Fibromyalgia pain and fatigue.

Contraindications

Treatment with sedative hypnotic agents; succinic semialdehyde dehydrogenase deficiency; hypersensitivity to any component of the product.

Dosage and Administration

Adults

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 Impairment
Adults

PO Reduce starting dose 50%; titrate dose increments to effect while closely monitoring potential adverse reactions.

General Advice

  • Allow at least 2 h after eating before taking first dose.
  • Variability in the timing of dosing in relation to meals should be minimized.

Storage/Stability

Store at 59° to 86°F. Use diluted solutions within 24 h to minimize bacterial growth and contamination.

Drug Interactions

Alcohol, CNS depressants, sedative hypnotics

Possible additive or potentiated CNS depressant effects.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Increased BP (6%).

CNS

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%).

Dermatologic

Hyperhidrosis (6%); pruritus (at least 1%).

EENT

Blurred vision, nasopharyngitis, tinnitus (6%); ear pain, nasal congestion, vertigo (at least 1%).

GI

Nausea (40%); vomiting (23%); upper abdominal pain (11%); diarrhea, dyspepsia (9%); viral gastroenteritis (6%); anorexia, constipation, toothache (at least 1%).

Genitourinary

Enuresis (17%); UTI (at least 1%).

Metabolic-Nutritional

Decreased weight (at least 1%).

Musculoskeletal

Cataplexy (9%); back pain, muscular weakness (6%); arthralgia, myalgia, neck pain (at least 1%).

Respiratory

Pharyngolaryngeal pain (9%); upper respiratory tract infection (6%); bronchitis, cough, dyspnea, sinus congestion, sinusitis (at least 1%).

Miscellaneous

Pain, postprocedural pain (6%); activated pain trauma, chest pain, contusion, fall, influenza, influenza-like symptoms (at least 1%).

Precautions

Warnings

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

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.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established in patients younger than 16 yr of age.

Elderly

Closely monitor for impaired motor and/or cognitive function.

Labor and Delivery

Undetermined.

Hepatic Function

Patients with compromised liver function have an increased elimination t ½ and systemic exposure to sodium oxybate.

Hazardous Tasks

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.

CNS effects

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.

Drug abuse and dependence

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.

Immunogenicity

Positive antinuclear antibody tests have been reported.

Incontinence

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).

Respiratory effects

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.

Sleepwalking

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.

Sodium intake

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.

Tolerance

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.

Overdosage

Symptoms

Brief periods of apnea, incontinence of urine and feces, respiratory depression, unresponsiveness. Other reports are confounded by multiple drug ingestion.

Patient Information

  • Review details of the Xyrem Patient Success Program and treatment (including procedure for preparing and taking the prescribed doses) before initiating therapy. Ensure patient has reviewed and understands the contents of the Medication Guide. Advise patient to review the Medication Guide with each refill.
  • Advise patient that medication will be started at a low dose and then gradually increased no more often than every 2 wk until max benefit is obtained.
  • Caution patient that sodium oxybate must be taken in 2 doses, the first dose at bedtime while in bed, and the second dose 2.5 to 4 h later while sitting in bed. Advise patient to set an alarm clock to wake up to take second dose.
  • Advise patient that the second dose must be prepared prior to ingesting the first dose and should be placed in close proximity to the patient's bed.
  • Advise patient that if the second dose is missed, to skip it and not take the medicine again until the next night. Caution patient to never take 2 doses at the same time.
  • Caution patient not to take sodium oxybate at any time other than bedtime.
  • Advise patient that medication must be diluted with water before taking. Instruct patient to measure each dose using the supplied dosing syringe, and dilute each dose with 2 oz (60 mL, ¼ cup, or 4 tablespoons) of water, using the child-resistant dosing cups provided with the medication, before going to bed.
  • Advise patient that once medication has been diluted, it must be used within 24 h. Instruct patient to discard any unused diluted solution after 24 h because of risk of bacterial growth and contamination.
  • Advise patient that food reduces absorption and efficacy of medication and to take each dose on an empty stomach, several hours after a meal. Advise patient to try to minimize variability in the timing of dosing in relation to meals.
  • Caution patient that medication may be habit forming, to take as prescribed, and to not stop taking or change the dose unless advised by health care provider.
  • Caution patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Instruct patient to immediately notify health care provider if any of the following occur: abnormal behavior, abnormal thinking, confusion, depression, loss of consciousness, new or worsening snoring, sleepwalking, or trouble breathing while asleep.
  • Instruct patient to contact health care provider if symptoms do not appear to be getting better or worsen, or if bothersome adverse reactions (eg, dizziness, headache, nausea, sleep problems, urinary or fecal incontinence, vomiting) occur. Caution patient not to increase dose.
  • Advise patient that drug can cause drowsiness and/or impair judgment, thinking, or reflexes, and to not drive or perform other tasks requiring mental alertness or coordination for at least 6 h after taking sodium oxybate. Caution patient to use extreme care while engaging in hazardous occupations or activities on days following initial use of sodium oxybate until carryover effects are determined.

Copyright © 2009 Wolters Kluwer Health.

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