FDA requires lower recommended doses for certain sleep drugs


The U.S. Food and Drug Administration announced Jan. 10 new, lower dosing requirements for certain sleep drugs that contain zolpidem, including Ambien, Ambien CR, Edluar, and ZolpiMist. Ambien and Ambien CR are also available as generics. The move comes on the heels of new data from driving simulation and laboratory studies showing that zolpidem blood levels in some individuals may be high enough the morning after use to impair activities that require alertness, including driving.

"After analyzing these new data we felt it necessary to add new drug safety information to the labeling, including lowering of the recommended dose," Dr. Ellis Unger, director of the Office of Drug Evaluation in the FDA’s Center for Drug Evaluation and Research, said during a Jan. 10 teleconference. "We hope that use of lower doses of zolpidem will mean that less drug will be in the bloodstream in the morning hours. We urge health care professionals to caution all patients who use these products about the risks of next morning impairment for activities that require complete mental alertness."

For women, the FDA now recommends that the dose of zolpidem should be lowered from 10 mg to 5 mg for immediate-release products and from 12.5 mg to 6.25 mg for extended-release products. (Ambien and Ambien CR are also available as generics.) "We have learned rather recently that women appear to be more susceptible to the risk of next morning impairment, because they eliminate zolpidem more slowly from their bodies than men," Dr. Unger said, noting that reasons for this association remain unclear. The supposition that women are smaller in size, compared with men, "is the first thing that one would think of," he said. "But if you correct the drug level data for patient size, that doesn’t account for the difference between men and women [in how the drug is eliminated]." For men, the FDA advises health care professionals to consider these same lower doses (5 mg for immediate-release products and 6.25 mg for extended release products).

More details about the development can be found in a Drug Safety Communication that was issued concomitantly. Despite the new recommendations, Dr. Unger emphasized that patients who are currently taking the higher doses of these sleep drugs "should continue to take the drug as it’s been prescribed until they discuss their situation with their health care provider and figure out how to continue to take the medication safely. We know that each patient is unique. The appropriate dose should be discussed with their health care professional."

Dr. Unger also explained that next morning impairment is not limited to sleep drugs that contain zolpidem. "All sleep drugs have the potential to cause this," he said. "So for all sleep medications all health care professionals should prescribe the lowest dose that is capable of preventing insomnia. The lower doses will decrease the potential for next morning impairment. Patients who must drive the next morning or perform other activities requiring full alertness should talk to their health care professional about whether sleep medicine is appropriate for them."

He concluded his remarks by noting that the FDA is continuing to evaluate the risk of impaired mental alertness with other insomnia drugs, including those sold over the counter.

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