Regulatory Focus™ > News Articles > FDA to Require Sleep Drug Manufacturers to Alter Dosing Recommendation

FDA to Require Sleep Drug Manufacturers to Alter Dosing Recommendation

Posted 10 January 2013 | By

The US Food and Drug Administration (FDA) has announced that it will require the manufacturers of widely used sleep drugs containing the active ingredient zolpidem to lower the recommended doses contained within their products to hedge regulators' concerns that patients taking the drug were more likely to awake in a state that could impair activity such as driving.

That activity was of particular concern to FDA regulators, including Ellis Unger, director of the Office of Drug Evaluation I. " "To decrease the potential risk of impairment with all insomnia drugs, health care professionals should prescribe, and patients should take, the lowest dose capable of treating the patient's insomnia," said Unger. "Patients who must drive in the morning or perform some other activity requiring full alertness should talk to their health care professional about whether their sleep medicine is appropriate."

The new requirements, he said, are aimed at making sure patients wake up with a reduced amount of zolpidem remaining in the blood stream, reducing the chance that they will get into an accident or otherwise harm themselves or others by participating in an activity while impaired. "In some individuals, zolpidem blood levels the morning after use appear capable of impairing driving to a degree that increases the risk of a motor vehicle accident," FDA officials wrote.

"Over the years, FDA has received spontaneous adverse event reports of driving impairment and motor vehicle accidents associated with zolpidem, but these reports lacked the information necessary to fully understand whether and how zolpidem affected people's mental alertness and ability to drive," Unger continued. "Recently, data from clinical trials and other types of studies have become available, which allowed FDA to better characterize the risk of next-morning impairment."

Affected drugs include Sanofi's Ambien and Ambien CR, Meda Pharmaceuticals' Edluar and Novadel's Zolpimist, a spray version of the drug. Another drug, Intermezzo, a lower-dose zolpidem product, already meets the proposed changes, FDA said.

Prior to the changes, the drugs were prescribed at either the 10mg or 12.5mg doses. The new proposed dosing recommendations will see men and women prescribed to differently, something Unger referred to as "unusual."


Current Drug Label

Proposed Drug Label

Ambien, Edluar, Zolpimist

Men and Women: 10 mg once daily

Women: 5 mg once daily

Men: 5 or 10 mg once daily

Ambien CR

Men and Women: 12.5 mg once daily

Women: 6.25 mg once daily

Men: 6.25 or 12.5 mg once daily

In a press call, Unger also said that future zolpidem-based drugs will be "required to submit driving study data" to support approval, and that all other sleep aid drugs will benefit from driving simulation studies as well. "One driving study will be sufficient for a drug so long as it is conducted well," explained Unger. The agency is reportedly in the process of assessing other sleep drugs and will make determinations about requirements at a later date.

Unger added that the process for making changes to the drug's labeling will be required within 30 days, as prescribed under the FDA Amendments Act of 2007.

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