Pharmaceutical Approval Update: Sodium Oxybate Oral Solution (Xyrem)

Sodium Oxybate Oral SolutionSodium Oxybate Oral Solution (Xyrem)

Manufacturer: Jazz Pharmaceuticals, Palo Alto, CA Indication: Sodium oxybate is indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug was originally approved as the first and only treatment for cataplexy in patients with narcolepsy. (Cataplectic patients experience a sudden loss of muscle tone and fall to the floor.)

Biological Class: Sodium oxybate is a sodium salt of gamma-hydroxybutyrate (GHB). GHB is a substance that is frequently abused when acquired illicitly and used illegally.

Uniqueness of Drug: Sodium oxybate is a Schedule III drug under the Controlled Substances Act and is available only through a restricted distribution system called the Xyrem Success Program. silagra tablets

Boxed Warning: This is a CNS depressant with abuse potential and should not be used with alcohol or other CNS depressants.

Abuse of GHB has been associated with CNS adverse drug events (ADEs), including death. Even at recommended doses, its use has been associated with confusion, depression, and other neuropsychiatric events. Almost all of the patients who received sodium oxybate during clinical trials were receiving CNS stimulants; whether this affected respiration at night is unknown.

Important ADEs associated with abuse of GHB include seizures, respiratory depression and profound decreases in levels of consciousness, with some instances of coma and death. For people who were using GHB for recreational purposes, the circumstances surrounding the ADEs have not always been clear. For example, the dose of GHB taken, the nature and amount of alcohol imbibed, or any concomitant drugs ingested could not always be determined.

Under the Xyrem Success Program, this agentis made available to prescribers through a single centralized pharmacy and with the following procedures:

1. The prescriber contacts the centralized pharmacy, which provides educational materials that explain the drug’s risks and proper use as well as details of the program. canadian antibiotics

2. After the prescriber reads the materials and returns the necessary form, the pharmacy ships educational materials to the patient.

3. After it has been documented that the patient has read the materials, the drug is shipped to the patient.

The program also provides for detailed surveillance. Patients are to be seen no less frequently than every three months, and physicians are expected to report all serious ADEs to the manufacturer and to disseminate information to help minimize the risks of inadvertent use.


Incontinence. During clinical trials, 9% of narcoleptic patients receiving sodium oxybate experienced either a single episode of sporadic nocturnal urinary incontinence; fewer than 1% experienced a single episode of nocturnal fecal incontinence. Fewer than 1% of patients discontinued taking the drug as a result of incontinence. Incontinence was reported for all doses tested.
If a patient experiences urinary or fecal incontinence during therapy, the prescriber should attempt to rule out underlying causes, such as worsening sleep apnea and nocturnal seizures. However, there is no evidence to suggest that incontinence has been associated with seizures in patients treated with this agent.

Sleepwalking. The term “sleepwalking” refers to confused behavior occurring at night and, at times, behavior that is associated with wandering. It is unclear whether these episodes correspond to true somnambulism, which is a para-somnia occurring during non-rapid-eye movement sleep, or to any other specific medical disorder.

Sleepwalking was reported in 7% of 448 treated patients in clinical trials. Fewer than 1% of these patients discontinued therapy because of sleepwalking. In controlled trials of up to four weeks’ duration, the incidence of sleepwalking was 1% with both placebo and sodium oxybate. In one independent uncontrolled trial, sleepwalking was reported by 32% of treated patients for periods up to 16 years. Fewer than 1% of these patients stopped taking sodium oxybate because of sleepwalking.

Several instances of significant or potential injury were associated with sleepwalking during one trial. These included a patient falling down, clothing being set on fire while the patient attempted to smoke, the attempted ingestion of nail polish remover, and an overdose of oxybate. Episodes of sleepwalking should be fully evaluated, and appropriate interventions should be considered. suhagra

Sodium Intake. Daily sodium intake in patients taking sodium oxybate ranges from 0.5 g for a 3-g dose to 1.6 g for a 9-g dose. The dosage should be considered in patients with heart failure, hypertension, or compromised renal function.

Hepatic Insufficiency. Patients with compromised liver function have an increased elimination half-life and systemic exposure to sodium oxybate. The starting dose should therefore be decreased by one-half in such patients, and patient responses to dose increments should be monitored closely.

Renal Insufficiency. No studies have been conducted in patients with renal failure. Because less than 5% of sodium oxybate is excreted via the kidneys, no dose adjustment should be necessary in patients with renal impairment. The sodium load associated with the administration of sodium oxybate should be considered in patients with renal insufficiency.

Dosage and Administration. The dose varies among patients. The usual initial dose is 1.5 g at bedtime and three to four hours later. The usual maximal dose is 4.5 g at bedtime and three to four hours later. Carefully monitored higher doses may sometimes be required.

Commentary: GHB is a natural substance, found in cells throughout the body. Approximately 150,000 Americans are afflicted with narcolepsy. Research shows that GHB is an excellent treatment against narcolepsy and is definitely beneficial for such patients.

Given at bedtime, GHB reduces the number of daytime sleep attacks, cataplexy, hypnogogic hallucinations, and sleep paralysis.
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GHB is also effective in reducing nocturnal sleep disruptions and consolidating nocturnal sleep. It is associated with an “alerting effect” during the day; that is, patients seem to be able to cope with a lower dose of stimulant medication and are able to stay alert during the day.

Because sodium oxybate is a Schedule III drug under the Controlled Substances Act and is available only through a restricted distribution system, there is adequate protection against abuse. The expanded indication for use in treating excessive daytime sleepiness is a positive therapeutic achieve­ment for patients with narcolepsy.

Category: Blood Pressure Drugs

Tags: Erlotinib, Nelarabine, Xyrem

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