Xyrem - sodium oxybate

What is Xyrem?

Xyrem is an oral solution containing the active substance sodium oxybate (500 mg / ml).

What is Xyrem used for?

Xyrem is used in the treatment of narcolepsy with cataplexy in adult patients. Narcolepsy is a sleep disorder that causes excessive daytime sleepiness. Cataplexy is a symptom of narcolepsy characterized by a sudden muscle weakness caused by strong emotions such as anger, fear, joy, laughter or surprise. Sometimes cataplexy can cause falls.

Because the number of patients with narcolepsy is low, the disease is considered "rare" and Xyrem was designated an "orphan medicine" (a medicine used in rare diseases) on 3 February 2003.

The medicine can only be obtained with a special prescription.

How is Xyrem used?

Xyrem therapy should be started and performed under the guidance of a doctor experienced in treating sleep disorders. Due to the potential abuse of sodium oxybate, the doctor must

evaluate patients with a positive history of drug abuse.

The dose is 4.5 up to 9 g per day, divided into two equal doses. The maximum daily dose is 9 g. The recommended starting dose is two doses of 2.25 g (4.5 ml) per day. The dosage can then be adjusted at one to two week intervals based on the patient's response. In patients with liver disorders the initial dose should be halved. Patients with kidney problems must follow a low sodium intake diet. Patients taking Xyrem should avoid the use of alcoholic beverages, as alcohol can enhance the effects of the drug.

Xyrem is supplied with a graduated measuring device and a measuring cup. Before taking, each dose of Xyrem must be diluted in water. The first dose of the day should be taken before bedtime, at least 2-3 hours after a meal. The second dose should be taken 2.5-4 hours later. For more information, see the package leaflet.

How does Xyrem work?

The active substance in Xyrem, sodium oxybate, is a depressant of the central nervous system. The precise mechanism of action of sodium oxybate is not yet known, but it is believed that this substance binds to specific receptive molecules present on the surface of some brain cells. In this way it induces changes in brain activity, favoring slow-wave (delta) sleep and stabilizing nocturnal sleep. When taken before bedtime, Xyrem increases deep sleep and nighttime sleep, thereby decreasing the number of sleep attacks during the day. This improves the symptoms of narcolepsy.

How has Xyrem been studied?

The effects of Xyrem in narcolepsy with cataplexy were examined in 707 patients over four studies. In all of the studies, Xyrem was given at a daily dose of 3 to 9 g and compared with placebo (a dummy treatment). The first study (136 patients) examined the effects of Xyrem on the number of cataplexy episodes during 4 weeks of treatment. The second study, conducted on 56 patients treated with Xyrem for at least 6 months, compared a group of patients who continued treatment at the dose established with a group instead switched to placebo. The study measured the number of cataplectic episodes over 2 weeks. The other two studies (516 patients) analyzed the effects of Xyrem on excessive daytime sleepiness and on other symptoms of narcolepsy, both in monotherapy and in association with the therapy already taken by the patient (modafinil: a stimulant used to treat narcolepsy). The main measure of effectiveness was the change in daytime sleepiness.

What benefit has Xyrem shown during the studies?

Xyrem was more effective than placebo in reducing symptoms. In the first study, the daily dose of 9 g reduced the number of cataplexy episodes by 16.1 (from 23.5 to 8.7) a week compared to a decrease of 4.3 per week in placebo-treated subjects. The second study showed that Xyrem continued to prevent cataplexy attacks after long-term treatment: the number of episodes in patients who continued treatment with Xyrem remained unchanged over 2 weeks, while in the subjects who were after the placebo there was an increase of 21.0. Xyrem also reduced daytime sleepiness in both patients who continued to take modafinil and those who received Xyrem alone.

What is the risk associated with Xyrem?

The most commonly reported adverse reactions with Xyrem (in more than 1 in 10 patients) are dizziness, headache and nausea. Nausea is more common in women than in men. Xyrem can also cause respiratory depression (inhibition of breathing). For the full list of all side effects reported with Xyrem, see the Package Leaflet.

Xyrem should not be used in people who may be hypersensitive (allergic) to sodium oxybate or any of the other substances. It must also not be taken by people with "deficiency of succinic semialdehyde dehydrogenase (a rare metabolic disorder) or by people treated with opioid drugs (such as some painkillers) or barbiturates (for example, some anesthetics and medicines used to prevent seizures). Because of the potential for abuse of sodium oxybate, the doctor must carefully evaluate patients taking Xyrem.

Why has Xyrem been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Xyrem's benefits are greater than its risks for the treatment of narcolepsy with cataplexy in adult patients. Although the 9 g dose was the most effective, high levels of adverse reactions were observed with this dose, so the committee recommended an initial dose of 4.5 g per day. Since the effective dose is close to that for which the side effects become serious, dose increases should be carried out strictly under the supervision of a doctor who specializes in treating sleep disorders. The committee recommended that Xyrem be given marketing authorization.

What measures are being taken to ensure the safe use of Xyrem?

The company that makes Xyrem will reduce the risk of drug abuse by providing information material to healthcare professionals and patients, strictly controlling the distribution of the medicine and monitoring its use.