Safety Information

Contraindications

Sodium oxybate is contraindicated in patients being treated with sedative hypnotic agents.

Sodium oxybate is contraindicated in patients with succinic semialdehyde dehydrogenase deficiency. This rare disorder is an inborn error of metabolism variably characterized by mental retardation, hypotonia, and ataxia.[1]

Warnings

XYREM^® is a CNS depressant and should not be used in combination with alcohol, sedative hypnotics, or other CNS depressants[1]
Potential to impair respiratory drive. Use caution in patients with already compromised respiratory function
Elderly patients should be monitored closely for impaired motor and/or cognitive function when taking XYREM, as there is limited experience in this group[1]
Both doses should be taken when seated in bed
Patients should not drive or operate machinery for at least 6 hours after taking XYREM
In clinical trials of patients treated with XYREM (n=717):
- 2.6% of patients experienced confusion
- 3.2% reported depressive symptoms
- Other neuropsychiatric events included psychosis, paranoia, hallucinations, and agitation. Two suicides and one attempted suicide were recorded in patients with a previous history of depressive psychiatric disorder.[1]

Precautions for special populations

Daily sodium intake should be considered in patients with heart failure, hypertension, or compromised renal function.
Patients with compromised liver function should have their starting dose decreased by one half and response to dose increments monitored closely.
Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed.
Safety and effectiveness in patients under 16 years of age have not been established.
See full Prescribing Information for precautions about sleepwalking (4% in clinical trials) and incontinence (7% in clinical trials).[1]

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]

Boxed warning

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

References:

^ XYREM (sodium oxybate) [prescribing information]. Palo Alto, Calif: Jazz Pharmaceuticals; 2005.

Important Safety Information

1. XYREM^® is a controlled substance. Controlled substances are medicines that, if abused, may lead to varying degrees of physical or psychological dependence. XYREM is a Schedule III drug — which means that it has a moderate dependence liability. If you sell, distribute, or give your XYREM to anyone else or use it for purposes other than what it was prescribed for, you may be punished under federal and state law by jail and fines.

2. It is very important to keep XYREM out of reach of children and pets.

3. XYREM can cause serious side effects including trouble breathing while asleep, confusion, abnormal thinking, depression and loss of consciousness. Tell your doctor if you have any of these problems while taking XYREM.

BOXED WARNING:

!Warning

Central Nervous System Depressant with Abuse Potential. Should not be used with alcohol or other CNS depressants. Sodium oxybate is a form of GHB, a known drug of abuse. Abuse has been associated with some important central nervous system (CNS) adverse events (including death). Even at recommended doses, use has been associated with confusion, depression, and other neuropsychiatric events. Reports of respiratory depression occurred in clinical trials. Almost all of the patients who received sodium oxybate during clinical trials were receiving CNS stimulants.

Important CNS adverse events associated with abuse of GHB include seizure, respiratory depression and profound decreases in level of consciousness, with instances of coma and death. For events that occurred outside of clinical trials, in people taking GHB for recreational purposes, the circumstances surrounding the events are often unclear (e.g., dose of GHB taken, the nature and amount of alcohol or any concomitant drugs).

XYREM is available through the XYREM Success Program^®, using a centralized pharmacy 1-866-XYREM88^® (1-866-997-3688). The Success Program provides educational materials to the prescriber and the patient explaining the risks and proper use of sodium oxybate, and the required prescription form. Once it is documented that the patient has read and/or understood the materials, the drug will be shipped to the patient. The XYREM Success Program also recommends patient follow-up every 3 months. Physicians are expected to report all serious adverse events to the manufacturer.