FDA Requires Stronger Boxed Warnings for Insomnia Medication Adverse Events

FDA Acting Commissioner Ned Sharpless, MD

Ned Sharpless, MD

The FDA has announced that it will require an additional boxed warning to be added to the label of certain prescription treatments for insomnia: eszopiclone (Lunesta, Sepracor), zaleplon (Sonata, Pfizer), and zolpidem (Ambien, Sanofi-Aventis; as well as Ambien CR, Edluar, Intermezzo, and Zolpimist).¹

The Drug Safety Communication’s boxed warning, which is the agency’s most prominent, has been issued as a response to a number of reports of rare, but serious and varying complex sleep behaviors resulting in injuries and deaths after taking these medications.

“We recognize that millions of Americans suffer from insomnia and rely on these drugs to help them sleep better at night,” said acting FDA Commissioner Ned Sharpless, MD, in a statement. “While these incidents are rare, they are serious and it’s important that patients and health care professionals are aware of the risk. These incidents can occur after the first dose of these sleep medicines or after a longer period of treatment and can occur in patients without any history of these behaviors and even at the lowest recommended doses.”

Ultimately, the FDA advised patients to halt their insomnia medication and contact their healthcare provider if complex sleep behaviors occur which result in them engaging in activities while they are not fully awake or that they do not recall. The agency advised against prescribing eszopiclone, zaleplon, or zolpidem to patients who have previously experienced these complex sleep behaviors after taking any of those medicines.²

Healthcare professionals are being asked to notify all patients that although the incidents are rare, the behaviors caused by these medicines have led to serious injuries or death, and that they should discontinue the medicine upon any occurrence of an episode of complex sleep behavior.

“Today’s action is an important step in our ongoing effort to call more attention to these critical safety issues and serves as an example of our ongoing commitment to ensuring that patients and health care professionals have the information they need to make informed treatment decisions,” Sharpless said.

The medications’ current drug labels already include the association between complex sleep behaviors and the drugs, as well as additional safety issues which have arisen for each individual medication.

The FDA reviewed 66 cases which were reported to the FDA Adverse Event Reporting System or recorded in the literature, which included 46 reports of non-fatal serious injuries, including accidental overdoses, falls, burns, near-drowning, exposure to extreme cold temperatures leading to loss of limb or near death, and self-injuries such as gunshot wounds and apparent suicide attempts. The additional 20 reports were fatal incidents and included carbon monoxide poisoning, drowning, fatal falls, hypothermia, fatal motor vehicle collisions with the patient driving, and apparent suicide.

“We have closely watched the safety profile of these drugs since they were approved. When our ongoing safety monitoring recently reflected the risk of more serious injuries and deaths from patients on these medications who experienced complex sleep behaviors, we determined there was a need to take stronger steps to inform the public,” said Janet Woodcock, MD, director, FDA Center for Drug Evaluation and Research, in a statement. “We’ll continue to monitor and evaluate these risks associated with insomnia medications and communicate with the public or consider further actions, as appropriate.”

The FDA advises health care professionals and patients to report adverse events from eszopiclone, zaleplon, zolpidem or other medicines to the FDA’s MedWatch program.

REFERENCES

1. FDA requires stronger warnings about rare but serious incidents related to certain prescription insomnia medicines [press release]. Silver Spring, MD: Published April 30, 2019. fda.gov/news-events/press-announcements/fda-requires-stronger-warnings-about-rare-serious-incidents-related-certain-prescription-insomnia. Accessed April 30, 2019.

2. FDA Boxed Warning. Certain Prescription Insomnia Medicines: New Boxed Warning - Due to Risk of Serious Injuries Caused by Sleepwalking, Sleep Driving and Engaging in Other Activities While Not Fully Awake. FDA website. Published April 30, 2019. fda.gov/safety/drug-safety-labeling-changes/certain-prescription-insomnia-medicines-new-boxed-warning-due-risk-serious-injuries-caused. Accessed April 30, 2019.