BETHESDA, MD 10 January 2013—FDA this morning announced safety-related changes to the labeling for zolpidem-containing drugs, including a recommendation to halve the recommended dosage for women.
Ellis Unger, a director in FDA's Office of New Drugs, said that new pharmacokinetics data from driving-simulation studies show that after taking a nighttime dose of zolpidem, enough drug may remain in the patient's bloodstream the next morning to impair driving and other activities that require alertness.
According to FDA, extended-released formulations of these sleep medications are more likely than immediate-release products to cause morning impairment, but the problem occurs with all versions of the drug.
To combat the problem, FDA is requiring that manufacturers revise the dosage recommendations in the labeling for zolpidem-containing extended- and immediate-release drug products.
For immediate-release zolpidem products, the new recommended dosage for women is 5 mg taken once daily at bedtime. For men, the revised labeling recommends 5 or 10 mg taken once daily at bedtime.
The new dosage recommendation for extended-release products is 6.25 mg taken at bedtime for women and 6.25 or 12.5 mg taken at bedtime for men.
The labeling for Intermezzo, a sublingual formulation of zolpidem, already recommends a reduced dosage of the drug for women.
Unger said it's very unusual for FDA to recommend different drug dosages for men and women.
"We've learned here, rather recently, that women appear to me more susceptible to the risk of next-morning impairment because they eliminate zolpidem from their bodies more slowly than men," he explained.
He said it is not known why men and women metabolize the drug at different rates.
According to FDA, the revised labeling will state that the lower dosage is effective for many men, and prescribers should consider starting men at that dosage. The labeling will also state that the dosage can be increased for men and women, if necessary, but will increase the likelihood of next-morning impairment.
Although today's action applies only to zolpidem-containing drugs, the agency views next-morning impairment as a general risk of insomnia remedies.
"All sleep drugs have the potential to cause this," Unger said. "For all sleep medications, health care professionals should prescribe and patients should take the lowest dose that's capable of preventing insomnia."
Unger said FDA will require drug companies with insomnia treatments under review to perform driving-simulation studies as part of the approval process. He said the agency has requested but not demanded similar data from manufacturers of marketed insomnia drugs other than zolpidem.
"We want driving data on all of the sleep medications," he said.