New data from the FDA is forcing makers of zolpidem sleep aids to knock back the recommended doses of the drugs, and the agency is adding a label change that prompts physicians to make gender-based dose recommendations.
The regulator said in conference call Thursday that the new recommended doses will be 5mg for immediate-sleep versions of the drug and 6.25mg for extended release iterations. The new guidelines will affect drugs including Sanofi's Ambien, Ambien CR and generic versions thereof. Transcept/Purdue Pharma drug Intermezzo, which is also a zolpidem sleep aid, will not have to issue a new label, as its 3.5mg dose is below the FDA's new threshold, but the drug makers' driving study is the force behind the FDA's new guidelines.
“Risk mitigation is a difficult business,” Ellis Unger, of the FDA's Center for Drug Evaluation and Research said, by way of explaining that patients will awaken with levels of zolpidem in their bloodstreams, but at lower levels, with the new recommendations.
Despite the lower dose, Intermezzo's PI also includes warnings that consumers may be impaired in the morning.
Unger said the agency had received adverse event reports for drugs zolpidem drugs since 2007, but could not create a one-to-one connection with effects such as impaired driving because driving incidents could have been associated with additional factors such as consumption of other drugs or alcohol, or when the sleep aid had been taken. The Intermezzo driving studies, which accompanied the drug maker's application, changed that.
The agency was able to use the Intermezzo driving studies as backdrop for other information the regulator already had on hand from other manufacturers. Cross-referencing the information allowed the agency to conclude that the blood levels of the other drugs were associated with morning impairment. Unger said the information check was not prompted by a particular incident, but was done because the agency had the data to do it.
Unger said that although all sleep drugs have drowsiness listed as a side effect, the new information is distinct because “alertness can be impaired even in people who don't feel drowsy.” He also said the gender-based recommendation is due to the different ways men and women metabolize the agent: women need a lower dose because it stays in their blood longer.
Unger said that the driving study will be sufficient for current zolpidem drugs, but that the agency does want driving information on all sleep aids and this latest finding will mean applications for new sleep aids will have to be accompanied by driving data.
Consumers are also advised to keep taking their sleep aids until they can discuss doses with their physicians. Data from the Centers for Disease Control shows that eliminating a drug for sleeplessness can also have an effect – its latest data, from 2009, shows that 7.2% of sleep deprived 25-to-35-year-olds fell asleep while driving, and 5.7% of sleepy adults between 35 and 45 also nodded behind the wheel. The CDC said the National Transportation Safety Board estimates that “drowsy driving” is linked to almost 1,600 deaths and 40,000 nonfatal injuries every year.
Although the new safety information could be read as giving Intermezzo an edge, spokeswoman Libby Holman told MM&M in an email that it does not expect the latest news from the FDA will boost sales. Holman, who also noted that the drug has different indication than those of Ambien and its peers (it is for patients with interrupted sleep), also said the company does not expect today's news will alter the DTC campaign that started running in November 2012 and will continue through March. Intermezzo already includes a gender-based dosing recommendation.