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The Xyrem® Risk Management Program

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Abstract

Sodium oxybate, also known as gamma-hydroxybutyric acid (GHB), was discovered in 1960 and has been described both as a therapeutic agent with high medical value and, more recently, a substance of abuse. The naturally occurring form of this drug is found in various body tissues but has been studied most extensively in the CNS where its possible function as a neurotransmitter continues to be studied. Sodium oxybate has been approved in different countries for such varied uses as general anaesthesia, the treatment of alcohol withdrawal and addiction, and, most recently, cataplexy associated with narcolepsy.

During the 1980s, easy access to GHB-containing products led to various unapproved uses, including weight loss, bodybuilding and the treatment of sleeplessness, sometimes with serious long-term effects. The availability of these unapproved and unregulated forms of the drug led to GHB and its analogues1 being popularised as substances of abuse and subsequent notoriety as agents used in drug-facilitated sexual assault, or ‘date rape’, eventually leading to the prohibition of GHB sales in the US.

Legal efforts to control the sale and distribution of GHB and its analogues nearly prevented the clinical development of sodium oxybate for narcolepsy in the US. However, following extensive discussions with a variety of interested parties, a satisfactory solution was devised, including legislative action and the development of the Xyrem® Risk Management Program.

Amendments to the US Controlled Substances Act made GHB a schedule I drug, but also contained provisions that allow US FDA-approved products to be placed under schedule III. This unique, bifurcated schedule for sodium oxybate/GHB allowed the clinical development of sodium oxybate to proceed and, in July 2002, it was approved by the FDA as an orphan drug for the treatment of cataplexy in patients with narcolepsy as Xyrem® (sodium oxybate) oral solution.

To promote the safe use of sodium oxybate, as well as alleviate concerns over possible diversion and abuse following product approval, a proprietary restricted drug distribution system was created, called the Xyrem® Success ProgramSM. Components of the programme include a centralised distribution and dispensing system, a physician and patient registry, compulsory educational materials for patients and physicians, a specially trained pharmacy staff, a method for tracking prescription shipments, and an initial post-marketing surveillance programme. The system has created a unique opportunity to provide both physician and patient education and ongoing patient counselling, promoting greater drug safety and enhanced patient compliance.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

  2. In the US, only federal agencies may impose such restrictions.

  3. Off-label use refers to the use of a drug for a purpose other than the approved indication.

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Acknowledgements

The authors of this manuscript are all employees of Orphan Medical Inc.

The authors wish to acknowledge Patti Engel, President and CEO of Engage Health and Bob Gagne, Public Affairs Counsel of Colle & McVoy and the many, many stakeholders involved in this project who together helped make the Xyrem® Risk Management Program possible. The authors have no conflicts of interest that are directly relevant to the contents of this manuscript.

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Authors and Affiliations

  1. Orphan Medical Inc., 13911 Ridgedale Drive, Suite 250, Minnetonka, Minnesota, 55305, USA

    David E. Fuller,  Carl S. Hornfeldt, Judy S. Kelloway, Pamela J. Stahl & Todd F. Anderson

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  1. David E. Fuller
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  2. Carl S. Hornfeldt
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  3. Judy S. Kelloway
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  4. Pamela J. Stahl
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  5. Todd F. Anderson
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Corresponding author

Correspondence to Carl S. Hornfeldt.

Additional information

In this article, the term analogue refers to substances that are either structurally related to, or have pharmacological activity similar to GHB.

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Fuller, D.E., Hornfeldt, C.S., Kelloway, J.S. et al. The Xyrem® Risk Management Program. Drug-Safety 27, 293–306 (2004). https://doi.org/10.2165/00002018-200427050-00002

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