By Yatin Shah
On May 14, 2013, the FDA issued a much-delayed safety alert concerning next-day sleepiness and increased risk of traffic accidents caused by a group of drugs containing zolpidem (sold as Zolfresh, Zoldem, Nidra, Zleep, etc. in India, and Ambien, Edluar, Intermezzo, etc. in the United States), which are widely-prescribed insomnia drugs. Zolpidem has also been linked to next-day memory loss of activities from the previous night. The drug was approved in November 2011, despite concerns about high levels of the drug remaining in the blood the morning after administration, which had led to two previous FDA rejections.
Since approval, FDA has received 700 reports of driving mishaps. Although blood tests were positive for zolpidem in those incidents, the information received by FDA through their Adverse Event Reporting System did not definitively conclude that zolpidem was the cause of the accidents. But it has been shown that zolpidem exhibits tremendous individual variation. For instance, women exhibit higher levels of zolpidem in their blood than men, which is what led FDA to require a lower dose for women. And the American Geriatric Society marks zolpidem as a potentially inappropriate medication for the elderly because it has been shown that both elderly men and women exhibited an increased Cmax after drug administration.
Zolpidem also has varied metabolism, and it is almost impossible to predict the level of the drug in a given individual’s blood, how long the drug will stay in the body, and thus how any one individual will respond. The drug’s pharmacokinetic profile is characterized by rapid absorption from the gastrointestinal tract, and it has a short elimination shelf-life of 2.4 hours, although its duration in the system can be up to six hours, which varies depending on whether you’re male or female. Total protein binding was found to be 92.5 ± 0.1%, which shows that the protein binding results in a long action time for the drug. The potentially long duration of zolpidem in the body, plus the patient-to-patient variation, ultimately makes it hard to know whether or not you’re safe in taking this medication.
Because of these concerns and the FDA’s safety alert, the Ministry of Health and Family Welfare in India (MOHFW) now covers zolpidem in Schedule H1. So with these concerns expressed by FDA, MOHFW, and many other organizations, are you going to risk that morning fender bender?