THURSDAY, June 7, 2001 (HealthDayNews) -- The government should approve the use of a controversial drug for temporary paralysis linked to narcolepsy, but not for daytime sleepiness associated with the condition, a divided panel of sleep experts recommended yesterday.
The panelists were more united in strongly urging the Food and Drug Administration (FDA) to make sure the drug, sodium oxybate, doesn't fall into the wrong hands. The advisory group to the FDA said the agency should develop a risk management plan for the medication.
The division was fitting given the controversy over the drug, which is made under the brand name Xyrem by Orphan Medical of Minnetonka, Minn. Xyrem's active ingredient is gamma-hydroxybutyrate (GHB), a controlled substance known as the "date-rape drug." GHB has been linked to at least 71 deaths and an estimated 5,500 emergency room visits for overdoses.
GHB, which is used as a sleep aid for anesthesia in Europe, became a controlled substance last year under the Date-Rape Drug Prohibition Act. The drug, and precursor chemicals like GBL, which the body converts into GHB, can kill by suppressing the central nervous system.
The panel voted 6-3 to recommend approval of 9-gram doses of Xyrem for the treatment of cataplexy, which is the sudden loss of muscle control that affects approximately 75,000 of the nation's 125,000 narcoleptics. The panel was divided 5-4 on whether 6 grams was effective for the sudden-sleeping condition.
However, they voted to discourage approval of the drug for treatment of excessive daytime sleepiness (EDS). The advisory group also divided 4-4, with one abstention, over whether Orphan Medical had shown convincing evidence of Xyrem's safety.
And by an 8-1 margin, the panelists said the FDA should come up with a risk-management plan for the drug, including limiting prescriptions to patients with narcolepsy marked by cataplexy.
Dr. LaRoy Penix, a neurologist at Morehouse School of Medicine in Atlanta and a member of the FDA panel, says he believes Xyrem would be useful for people with cataplexy. But he was among the specialists who didn't find it effective for EDS, and he voted with the group that found its safety data lacking.
"I had a question about the possibility of side effects," says Penix. Information from the company says Xyrem's side effects in clinical trials included dizziness, nausea, headaches, sleepwalking, and urinary incontinence during sleep, know as enuresis.
Penix says the abuse potential of the drug and the fact that it's a controlled substance led him to urge that, if the FDA approves Xyrem it should caution doctors to offer it only to patients with cataplexy. "Legally, we cannot [prevent off-label use of a drug], but I think it's highly recommended in this case," Penix says.
John Bullion, Orphan's chief executive officer, says the company is working with the FDA to minimize the risks of abuse of Xyrem by narrowing the way it will distribute the drug. Rather than use conventional distribution channels, Orphan has proposed to ship Xyrem through a single outlet, which will receive faxed requests from physicians and forward the drug by overnight courier to patients.
Such a system is now in place for a few other drugs, including thalidomide, Bullion says. To further reduce the risk of cheating, the pharmacy will call doctors who've written prescriptions for Xyrem to verify the order and keep track in a computer registry of how often it's prescribed and by whom. On the other end, patients or an approved nominee will have to sign for the package.
"It couldn't just be delivered to the house, dropped off and anyone sign for it," says Dr. William Houghton, Orphan's chief medical officer.
The FDA's decision should come by early July, Orphan says. Although the agency isn't bound by its panelists' advice, it generally follows their recommendations.
Last year, Stanford University researchers showed that most patients with narcolepsy lack the brain protein hypocretin, which appears to help promote wakefulness.
What To Do
For more on narcolepsy, check out the Narcolepsy Network or the Stanford Center for Narcolepsy.
To learn more about known uses of GHB, visit the U.S. Department of Justice.
