Xyrem

Xyrem (sodium oxybate) is a prescription medication manufactured by Jazz Pharmaceuticals, and is approved by the US Food and Drug Administration (FDA) for the treatment of cataplexy associated with narcolepsy and Excessive Daytime Sleepiness (EDS) associated with narcolepsy. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid.

The American Academy of Sleep Medicine (AASM) recommends Xyrem as a standard of care for the treatment of cataplexy, daytime sleepiness, and disrupted sleep due to narcolepsy in its Practice Parameters for the Treatment of Narcolepsy and other Hypersomnias of Central Origin. These recommendations are based upon careful review of the medical literature, and the designation "standard" of care "reflects a high degree of clinical certainty" based on strong empirical evidence.

Xyrem is a prescription medication used to treat narcolepsy, which is a rare medical condition that has been documented worldwide, with a prevalence ranging from 0.002% in Israel to 0.18% in Japan. Prevalence in the US is approximately 0.05%. The pentad of clinical symptoms includes: Excessive Daytime Sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis, and fragmented sleep. EDS and cataplexy are the most common daytime symptoms of narcolepsy.

Development

Xyrem is designated as an orphan drug, which is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy in many countries, and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development. In the last 20 years efforts have been made to encourage companies to develop orphan drugs. The Orphan Drug Act in the US (1983) was succeeded by similar legislation in Japan (1985), Australia (1997), and the European Community (2000).

The development of Xyrem (sodium oxybate) oral solution as a prescription medication was initiated by the Office of Orphan Products Development (OOPD). The OOPD is a department of the FDA dedicated to promoting the development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. In 1994, the OOPD petitioned a pharmaceutical company called Orphan Medical to investigate sodium oxybate as a potential treatment for narcolepsy. In 2002, Xyrem received approval from the FDA for the treatment of cataplexy in patients with narcolepsy.

There are also ongoing tests to see if Xyrem could prove helpful with other medical conditions, such as Parkinson's disease, chronic fatigue syndrome (ME), schizophrenia, binge eating, essential tremor and other non-Parkinson's movement disorders.

Mechanism of action

Cost

Orphan drugs by their nature are very specialized and have relatively few patients to spread the costs associated with bringing them to market. The average cost of a specialty drug in the US is $2,875 per month or $34,500 annually, however drug prices vary by country.

In European Union (EU) countries, the government either provides national health insurance (as in the UK and Italy) or strictly regulates quasi-private social insurance funds (as in Germany, France, and the Netherlands). These government agencies are the sole purchaser (or regulator) of medical goods and services and have the power to set prices. The cost of pharmaceuticals, including Xyrem, tend to be lower in these countries. and the effective dose range is 6–9 grams per night which equates to $1,950–2,925 per month. Xyrem is covered by most insurance plans including Medicare and Medicaid and approximately 90% of Xyrem patients have a flat monthly co-pay. 75% of Xyrem insurance copays are less than $50 and 42% are less than $25 for a one-month supply. The manufacturer offers a coupon program for the small number of patients with larger co-pays. Some insurance companies may require physicians to fill out an insurance form called a Prior Authorization as part of the prescribing process. Additionally, the manufacturer offers a Patient Assistance Program to patients that do not have insurance and are unable to afford their Xyrem prescription. Approximately 8% of Xyrem patients currently participate in this program and receive their prescription for free.

Existing US Patents on Xyrem prevent other companies from manufacturing it as a drug. Xyrem is protected by US Patents 6472431, and 6780889 which are set to expire in 2019 and 2022, respectively.

Distribution

A number of measures have been put in place by Xyrem's manufacture to ensure that it is used safely and appropriately. Xyrem requires a prescription and can only be obtained through a restricted distribution program, called the "Xyrem Success Program". This restricted distribution program is required by the FDA as part of a Risk Management Program (RMP) to manage product safety and prevent abuse.

The program involves many risk management components, such as:

Physician education

Registration

Patient education

Detailed patient surveillance

The program includes a single centralized pharmacy with a toll-free number.

Initial dosages are set by the prescribing physician. Each bottle of Xyrem is shipped with a graduated syringe (measured in grams) and two dosing cups. Each night, the patient mixes two doses with 60 ml of water (sometimes substituted with a calorie-free beverage to cover the unpleasant taste of the medication). The first dose is taken at bedtime, and the second is taken 2.5 to 4 hours later.

Safety

Xyrem has been safely used by patients with narcolepsy for more than seven years. In Canada and the European Union (EU), it is classified as a Schedule III and a Schedule IV controlled substance, respectively. Some patients treated with Xyrem have also experienced moderate to significant weight loss. This may be due to the fact that Xyrem improves sleep architecture and increases the length of deep sleep stages, resulting in increased production of human growth hormone (GH) and changes in energy metabolism.

Use by athletes

Xyrem has been instrumental in allowing cyclist Franck Bouyer to resume his career and is the only treatment for narcolepsy approved by the World Anti-Doping Agency.

See also

Narcolepsy

Cataplexy

Excessive daytime sleepiness

References

Further reading

External links

Xyrem Official Website Jazz Pharmaceuticals

Xyrem Package Insert

WebMD – Xyrem

Category:Orphan drugs Category:Sleep Category:Sleep medicine Category:Sleep disorders