Safety Information

Contraindications

• Concomitant therapy with sedative hypnotic agents
• Succinic semialdehyde dehydrogenase deficiency

Warnings

CNS depressant/respiratory effect

• Due to rapid onset of action, take XYREM® (sodium oxybate) only at bedtime while in bed
  • No hazardous occupations or activities requiring mental alertness or motor coordination for at least 6 hours after ingestion
• Combined use with alcohol (ethanol) may result in potentiation of CNS depressant effects
• Should not be used in combination with sedative hypnotics or other CNS depressants
• Potential to impair respiratory drive, especially in patiens with already-compromised respiratory function
  • In overdoses, life-threatening respiratory depression has been reported
• Confusion/neuropsychiatric events
  • In clinical trials, 2.6% of patients on sodium oxybate experienced confusion
  • Other neuropsychiatric events included psychosis, paranoia, hallucinations, and agitation
• Depression
  • In clinical trials, 3.2% of 717 patients on sodium oxybate reported depressive symptoms; in most cases, no change in treatment was required
  • 2 suicides and 1 attempted suicide were reported in trials in patients with previous history of depressive psychiatric disorder
  • Monitor patients with previous history of depressive illness and/or suicide attempt carefully
• Use in the elderly
  • Very limited experience with sodium oxybate in elderly patients
  • Monitor elderly patients closely for impaired motor or cognitive function

Precautions

• Consider the sodium load in patients with heart failure, hypertension, or compromised renal function
• Hepatic insufficiency
  • Patients with compromised liver function will have an increased elimination half-life.
  • The starting dose should therefore be decreased by one half in such patients, and response to dose increments should be monitored closely
• Drug interactions
  • Sodium oxybate did not produce pharmacokinetic interactions with
    • Modafinil (stimulant)
    • Zolpidem tartrate (hypnotic)
    • Protriptyline HCI (Tricyclic Antidepressants (TCA))
  • Pharmacodynamic interactions cannot be ruled out
• XYREM® (sodium oxybate) should not be used in combination with sedative hypnotics or other CNS depressants
• Nocturnal urinary incontinence
  • In 7% of patients treated with sodium oxybate in clinical trials
  • Has been reported at all doses tested
  • <1% of patients discontinued because of incontinence
• Sleepwalking
  • Observed in 4% of patients in clinical trials (n=717) with <1% discontinuation; 1% in controlled trials (n=655)
  • Episodes of sleepwalking should be fully evaluated and appropriate interventions considered
• Pregnancy Category B
  • There are no adequate and well-controlled studies in pregnant women
• Nursing mothers
• It is not known whether sodium oxybate is excreted in human milk
• Pediatric use
• Safety and effectiveness in patients under 16 years of age have not been established

Drug interactions

• When evaluated in formal studies, XYREM had no pharmacokinetic interactions with 3 drugs commonly used in narcolepsy:
  • Modafinil
  • Zolpidem tartrate
  • Protriptyline hydrochloride
• Pharmacodynamic interactions with these drugs cannot be ruled out
• XYREM does not inhibit CYP3A, CYP2C9, or CYP2D6, three of the most common cytochrome P450 isoenzymes involved in drug metabolism^[1]

The complete safety information is available in the full Prescribing Information.

© 2012 Jazz Pharmaceuticals Inc.