Safety overview of postmarketing and clinical experience of sodium oxybate (Xyrem): abuse, misuse, dependence, and diversion.
OBJECTIVE
This study reviewed the cumulative postmarketing and clinical safety experience with sodium oxybate (Xyrem), a treatment approved for cataplexy and excessive daytime sleepiness in narcolepsy. Study objectives were to investigate the occurrence of abuse/misuse of sodium oxybate since first market introduction in 2002, classify cases using DSM-IV criteria for substance abuse and dependence, and describe specific characteristics of these cases.


METHODS
We retrospectively reviewed postmarketing spontaneous adverse event (AE) reports from 15 countries for all cases containing reporting terminology related to abuse/misuse to determine its occurrence. All death cases independent of causality were reviewed to identify associated risk factors.


RESULTS
Approximately 26,000 patients worldwide received sodium oxybate from first market introduction in 2002 through March 2008. Of those 26,000 patients, 0.2% reported > or = 1 of the events studied. These included 10 cases (0.039%) meeting DSM-IV abuse criteria, 4 cases (0.016%) meeting DSM-IV dependence criteria, 8 cases (0.031%, including 3 of the previous 4) with withdrawal symptoms reported after discontinuation of sodium oxybate, 2 confirmed cases (0.008%) of sodium oxybate-facilitated sexual assault, 8 cases (0.031%) of overdose with suicidal intent, 21 deaths (0.08%) in patients receiving sodium oxybate treatment with 1 death known to be related to sodium oxybate, and 3 cases (0.01%) of traffic accidents involving drivers taking sodium oxybate. During this period, approximately 600,000 bottles of sodium oxybate were distributed, and 5 incidents (0.0009%) of diversion were reported.


CONCLUSIONS
Cumulative postmarketing and clinical experience indicates a very low risk of abuse/misuse of sodium oxybate.
Wang
Y Grace
YG
Jazz Pharmaceuticals, Inc. Palo Alto, CA 94304, USA. Grace.Wang@jazzpharma.com
Swick
Todd J
TJ
Carter
Lawrence P
LP
Thorpy
Michael J
MJ
Benowitz
Neal L
NL
D000063:Accidents, Traffic / Q000706:statistics & numerical data; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy*; D062787:Drug Overdose / Q000453:epidemiology; D004363:Drug Utilization; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D011358:Product Surveillance, Postmarketing; D011902:Rape / Q000706:statistics & numerical data; D012306:Risk; D012978:Sodium Oxybate / Q000009:adverse effects*; D019966:Substance-Related Disorders / Q000453:epidemiology
D002492:Central Nervous System Depressants; D012978:Sodium Oxybate