General Information

Xyrem (sodium oxybate) is a central nervous system (CNS) depressant.

Xyrem is specifically indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

Xyrem is supplied as an oral solution. 

Dosing in Adults:

The recommended starting dosage is 4.5 grams (g) per night administered orally, divided into two doses: 2.25 g at bedtime and 2.25 g taken 2.5 to 4 hours later. Increase the dosage by 1.5 g per night at weekly intervals (additional 0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later) to the effective dosage range of 6 g to 9 g per night orally. The dosage may be gradually titrated based on efficacy and tolerability. Doses higher than 9 g per night have not been studied and should not ordinarily be administered.

Dosing in Children:

Xyrem is administered orally twice nightly. The recommended starting pediatric dosage, titration regimen, and maximum total nightly dosage are based on patient weight, as specified in the drug label. The dosage may be gradually titrated based on efficacy and tolerability.

Side Effects

Adverse effects associated with the use of Xyrem oral solution may include, but are not limited to, the following:

• nausea
• dizziness
• vomiting
• somnolence
• enuresis
• tremor 
• headache
• weight decreased
• decreased appetite
• sleepwalking

The Xyrem drug label comes with the following Black Box Warning: Central Nervous System Depression: Xyrem is a CNS depressant, and respiratory depression can occur with Xyrem use.   Abuse and Misuse: Xyrem is the sodium salt of gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB is associated with CNS adverse reactions, including seizure, respiratory depression, decreased consciousness, coma, and death. Xyrem is available only through a restricted program called REMS.

Mechanism of Action

The mechanism of action of Xyrem in the treatment of narcolepsy is unknown. Sodium oxybate is the sodium salt of gamma-hydroxybutyrate (GHB), an endogenous compound and metabolite of the neurotransmitter GABA. It is hypothesized that the therapeutic effects of Xyrem on cataplexy and excessive daytime sleepiness are mediated through GABAB actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.

Clinical Trial Results

Xyrem was evaluated at 3 g, 6 g, and 9 g doses in a in a placebo-controlled, double-blind study. 136 subjects suffering from cataplexy associated with narcolepsy recorded their symptoms over a baseline period of two to three weeks after which they were treated with one of the three doses of Xyrem or placebo for a four-week period. Results of this study showed a 68.6% reduction in the median number of cataplexy attacks in subjects treated with 9 g dose of Xyrem compared to baseline. When compared to placebo, subjects receiving the 9 g dose of Xyrem showed a highly statistically significant clinical improvement. The 6 g dose of Xyrem approached significance, while the 3 g dose of Xyrem showed no statistical significance when compared to placebo. In a follow-on trial, in which 118 subjects continued taking Xyrem at clinically effective levels, the 6 g and 9 g Xyrem groups demonstrated maximum improvement at seven weeks and then sustained the clinical benefit throughout the rest of the 30-week treatment period.