The U.S. Food and Drug Administration (FDA) last month ordered
manufacturers of sedative/hypnotic medications to add stronger language to
their products' labels warning prescribers and patients of the potential for
anaphylactic reactions and angioedema. The agency also called for new language
warning of the potential for what it calls "complex sleep-related
In addition, the FDA is requiring manufacturers to send "Dear
Healthcare Practitioner" letters to prescribers outlining the new
warning language. Starting later this year, patients who fill prescriptions
for sedative/hypnotic medications will receive a required patient medication
guide with each prescription dispensed.
Russel Katz, M.D., director of the FDA's Division of Neurology Products,
said during a media conference call that the agency decided to order the new
warnings even though the events are "relatively rare" because the
events occur to patients who have taken a medication intended to alter their
level of consciousness and, as such, the patient may not be able to alert
anyone if an event were to occur.
Katz said the actual number of cases reported wasn't available; however, he
characterized the reports of anaphylactic reactions and angioedema as having
occurred with each of the 13 medications in the sedative/hypnotic category and
as possibly totaling as many as "several dozen."
Katz characterized the reports of "complex sleep-related
behaviors" as less common. "We became aware [of these problems]
about a year ago, based on reports that were made public, and we went back and
looked at all the drugs again," Katz told reporters.
While not all sedative/hypnotic medications are associated with reports of
complex sleep-related behaviors, "we've looked at the entire class and
believe that the entire class is capable of producing those events."
He noted that the FDA had received "a couple dozen" reports of
patients "driving, eating, making phone calls, and even having
sex" during the middle of the night, while "under the influence of
It isn't clear, Katz continued, whether the patients characterized in the
reports were awake or asleep, but "they were certainly able to engage in
complex behaviors such as driving." The behaviors, he added, aren't
simple sleepwalking. "People get out of bed, go get their keys, and they
go driving. That's very different from getting out of bed, taking a few steps,
and bumping into the wall."
Katz added that the reports of sleep driving and other sleep behaviors were
significantly more common in patients who had taken higher than labeled doses
of the medications, and they often combined the medication with alcohol.
Because the adverse-event reports that sparked the new warnings are
generated from spontaneous reports to the FDA's Adverse Events Reporting
System, it is nearly impossible to estimate how frequently the events may
occur. The only certainty, Katz said, is that the number of reports received
by the system is lower than the number of events that have actually
These are the 13 medications required to carry the new warnings:
More information on the FDA's warnings on sleep medications is