Sodium oxybate

This article describes the status of Xyrem as a prescription drug. To learn about the chemical and its biological mode of action, see the article on gamma-hydroxybutyric acid.

Xyrem is a trade name for gamma-hydroxybutyric acid or GHB, an endogenous neurochemical involved in regulating metabolism, especially regarding sleep or hibernation. In medical contexts GHB is often called sodium oxybate, which is an alternate term for the sodium salt of the chemical.

Approval process and legal status

GHB has a long history as a sleep aid, nutritional supplement, and recreational drug. In the 1980s research studies indicated that it was helpful as a treatment for narcolepsy, and in 2002 the company Orphan Medical was approved by the U.S. Food and Drug Administration (FDA) to market GHB as a treatment for narcolepsy with cataplexy. Jazz Pharmaceuticals, which acquired Orphan Medical in 2005, is currently conducting Phase III clinical trials to evaluate sodium oxybate for the treatment of fibromyalgia as well, based on clinical trials showing that it reduces pain and disability associated with the disease. Xyrem is currently marketed in the United States by Jazz Pharmaceuticals. There are also ongoing tests to see if Xyrem could prove helpful with other medical conditions, such as Parkinson's, Chronic Fatigue Syndrome (ME), and Schizophrenia.[1].

Xyrem is an orphan drug, meaning that the U.S. government recognizes it as worth developing even though the condition it treats is relatively rare. Orphan Medical received special incentives from the U.S. government for bringing it to market, in order to help them recoup the costs of testing. In this case Orphan Medical did not have any development expenses, since GHB is inexpensive to synthesize and was already recognized as a potential narcolepsy treatment. They did, however, need to gather extensive information demonstrating that the drug was safe, as well as showing low potential for addiction or tolerance when used under a doctor's supervision. They are also required to operate a distribution program that tightly controls who can receive Xyrem and under what circumstances. This process entails sending the package through FedEx Priority Overnight with direct signature required at a base cost of about $50 for a standard delivery compared to the average monthly cost of about $1.7k for treatment. Xyrem is distributed directly from the manufacturer and cannot be accessed by licensed pharmacists. It is therefore more tightly controlled than other drugs on Schedule III, and even some on Schedule II. This of course means that the manufacturer enjoys a larger share of the profits being that there are no middle men "adding value" to the pharmacoeconomic chain.

Xyrem is also the only drug to be on two drug schedules at once under U.S. law: GHB is on schedule I, meaning that it is considered a highly dangerous and addictive drug with no medical uses, but GHB marketed as Xyrem and prescribed for specific conditions is on schedule III, which includes many drugs considered safe when used properly. This is unusual because the schedule system is built around the assumption that a drug's risks are due to the chemical itself, without reference to the user or the circumstances of its use. However, the government cites pragmatic reasons for the distinction: recreational drugs are often of unknown origin, may contain contaminants, and are difficult to take at a precise dose, while the same substance in prescription form is easier to use as intended. The involvement of a doctor also helps reduce the risk of dependency or of recreational, rather than medical use. This is similar to the justification for offering Marinol under schedule III, while marijuana is schedule I, but it differs in that pharmaceutical THC (referred to as Marinol or dronabinol) is a pure version of one of the many active chemicals in marijuana, whereas GHB and Xyrem are chemically identical. The law is inconsistent in this regard, as other drugs such as amphetamine and fentanyl fall under a single schedule, regardless of whether they are in pharmaceutical form or have been illicitly synthesized for recreational use.

Criminal charges over marketing

In 2007, the makers of Xyrem, Orphan Medical, which is now part of Jazz Pharmaceuticals, pleaded guilty to a felony charge of marketing Xyrem for unapproved uses. These off-label uses included treatments for conditions such as fatigue, pain, and psychiatric disorders.

The lawsuit claimed that the manufacturers:

• Sponsored events where speakers bombarded the doctors with the message that Xyrem should be used to treat a variety of medical conditions;
• Paid unrestricted grants to physicians as a reward or inducement to prescribe Xyrem for off-label purposes;
• Targeted physicians who were already prescribing Xyrem for aggressive sales calls to encourage off-label prescriptions;
• Paid speaker fees to doctors who promoted the use of Xyrem for off-label purposes, such as insomnia and psychiatric disorders.

For example, one physician had made well over $100,000 in just one year for giving such speeches. The doctor, Peter Gleason, admitted to giving speeches and seminars without following "evidence-based guidelines". It was said that he once claimed "table salt is more dangerous" than Xyrem.

Cost

According to First DataBank price reporting service, the current WAC (Wholesale Acquisition Cost) of Xyrem is $800 (180 mL bottle, 500 mg/mL). The effective dose range of Xyrem is 6 to 9 grams per night which equates to a Wholesale Acquisition Cost of $1,600 - $2,400 per month. Wholesale Acquisition Cost (WAC) is the manufacturer’s reported list price for a prescription pharmaceutical for sale to wholesalers.

Xyrem is covered by most insurance companies 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 manufacture offers a coupon program for the small number of patients with larger copays. Some insurance companies may require physicians to fill out an insurance form called a Prior Authorization as part of the prescribing process.

Additionally, the manufacture offers a Patient Assistance Program to patients that are unable to afford their Xyrem prescription. Approximately 8% of Xyrem patients currently participate in this program and receive their prescription for free. Patients may learn more about this program or apply by contacting the XYREM Success Program for (1-866-XYREM88).

Xyrem Success Program

Xyrem is available by prescription only through a restricted distribution program, called the "Xyrem Success Program". This restricted program was implemented due to safety concerns associated with the use of Xyrem.

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 60ml of water, Crystal Light, or sugar-free Kool-Aid (water is sometimes substituted for Crystal Light or sugar-free Kool-Aid in order to improve the unpleasant taste of the medication). The first dose is taken at bedtime, and the second is taken 2.5 to 4 hours later.

Use by athletes

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

See also

• Gamma-hydroxybutyric acid
• Narcolepsy

External links

• Website for Xyrem