12-Month Evaluation Of A Novel Risk Management Program For Responsible Distribution Of Sodium Oxybate Treatment For Cataplexy

July 13, 2004

Stahl PJ, Nelson JA - Orphan Medical, Inc., Minnetonka, MN, USA
Ritzinger CA - Medical Information and Drug Safety, Orphan Medical, Inc., Minnetonka, MN, USA
Smith D - Specialty Distribution Services, Express Scripts, Inc., Maryland Heights, MO, USA

Xyrem® (sodium oxybate) oral solution, indicated as a treatment for cataplexy in patients with narcolepsy, was approved by the FDA in conjunction with a Risk Management Program in July 2002.

The program was designed to encourage appropriate use of Xyrem through physician and patient education while taking steps to minimize the risk for diversion. The ability of the Risk Management Program to limit diversion was evaluated following the first 18 months of commercial use beginning October 1, 2002. 

Although twenty-two reports of potential diversion have been received, there have been no reports of actual diversion. At this time it appears that the goals of the program are being met.

Introduction

Xyrem® (sodium oxybate) oral solution, indicated as a treatment for cataplexy in patients with narcolepsy, was approved by the FDA in conjunction with a Risk Management Program in July 2002. The active ingredient, sodium oxybate, is also known as GHB, a drug with a history of abuse.

The Risk Management Program was designed to maximize physician and patient education about the safe use of sodium oxybate and minimize potential diversion or abuse of the approved drug by limiting distribution through a central pharmacy.

The ability of the Risk Management Program to limit diversion was evaluated following the first 12 months of commercial use beginning October 1, 2002.

Methods

Four tools are employed to evaluate the effectiveness of the Risk Management Program in preventing diversion, defined as utilizing an otherwise legitimate product for an unlawful use: (1) Prescribers are proactively sent Post-Marketing Evaluation Program forms and requested to report “inappropriate use” of sodium oxybate at months 3 and 6 of treatment, including premature refill requests, reports of theft or loss, difficulty in using or preparing drug and “other” inappropriate use; (2) Prescriber credentials are verified prior to filling a prescription; additionally, the pharmacy maintains a registry of all valid prescribers. (3) The central pharmacy confirms delivery of each sodium oxybate shipment and reports theft, loss or other spontaneous reports of potential diversion; (4) A system is also in place for receiving and documenting spontaneous complaints or safety issue.

Results

By September 30, 2003, prescriptions had been filled for 2021 patients, and 334 Post-Marketing Evaluation Program reports were submitted for 228 unique patients. There were no reports of inappropriate use.

The screening of physician credentials resulted in the pharmacy declining registry of six physicians. Four Diversion Risk Reports included the reported theft of product from a patient’s car; report of non-delivery because a prescription delivery was left at a patient’s doorstep due to courier error; a bottle was inadvertently left at a hotel while traveling; and a hospital pharmacy lost a sodium oxybate supply bottle while a patient was hospitalized for an unrelated stay.

There was one case of accidental overdose and one incident of possible withdrawal syndrome was reported; however, in that case the reporter was unclear if the withdrawal symptoms were due to sodium oxybate, anticholinergic (diphenhydramine) toxicity or both.

Conclusion

The Risk Management Program was designed to encourage safe use of sodium oxybate through physician and patient education while taking steps to minimize the risk for diversion. There have been no reports of actual diversion through the Risk Management Program, although there were thirteen cases of potential diversion. At this time it appears that the goals of the program are being met.