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FDA Requests Stronger Label Warnings on Sleep Drugs

In March, the FDA asked manufacturers of sleeping pills to use stronger product label warnings about the risks of severe allergic reactions, severe facial swelling, and complex sleep-related behaviors, such as sleep-driving and sleep-eating.

Since December 2006, the FDA has been working with manufacturers to update labeling, notify health care providers about the new warnings, and develop medication guides to inform consumers about risks and precautions.

There have been anecdotal reports of complex motor behaviors like sleep-eating and sleep-driving, but no hard data from randomized, controlled studies on incidence, and experts told Neurology Today that the risk for these complex behaviors appears to be low because they do not occur that often.

But the experts also said they supported the FDA's insistence on stronger labeling to warn patients about side effects, and that patients should be encouraged to report adverse events and stop using sleeping drugs if they have problems. They noted that adverse effects could be avoided in almost all cases by following simple instructions, like not drinking alcohol with medication.


“Post-dose amnesia is most common with zolpidem (Ambien) and triazolam (Halcion), and this phenomenon is common in patients who delay going to bed or who take higher doses,” said Mark G. Goetting, MD, medical director of Sleep Health, a tertiary insomnia center in Portage, MI.

Michael H. Silber, MD, professor of neurology at the Mayo Clinic College of Medicine in Rochester, MN, said that sleep-eating is most often seen in patients taking zolpidem, perhaps because it is the most commonly prescribed hypnotic drug.

Experts commented, however, that they had not observed anaphylaxis (severe allergic reaction) and angioedema (severe facial swelling) related to these drugs, and it is uncertain as to whether the drugs carry a heavier risk of these effects than other medications.

The FDA list includes 13 drugs representing several pharmacological classes with different mechanisms of action and side effect profiles. While all sedative drugs have side effects, with the exception of ramelteon (Rozerem) — which is not associated with amnesia or complex motor behavior — most patients using these drugs benefit from them and do not suffer ill effects, Dr. Goetting emphasized.

Although the warnings should not discourage physicians from prescribing hypnotics to appropriate patients, said Dr. Silber, they may “cause clinicians to consider addressing the underlying factors causing sleep problems before quickly prescribing a medication,” Daniel Cohen, MD, noted. Dr. Cohen, a neurologist at Beth Israel Deaconess Medical Center and the Sleep Disorders Center affiliated with Harvard Medical School, added that physicians should be aware of alternative therapies such as cognitive-behavioral therapy, which could be as effective as hypnotics and carries less risk.

But one sleep specialist thought the FDA warning was more media-driven than good medicine. Clifford B. Saper, MD, PhD, chairman of the department of neurology at Harvard Medical School, said: “The problem of sleep behaviors has received a lot of press, but little study. We do not know the incidence with these drugs, or even if it occurs with many of them.” He continued, “I think they [FDA] are running scared because of recent bad publicity, and they are trying to look proactive and responsive to recent media stories. …This is just political grandstanding, not medicine.”


The revised labeling affects the following 13 products:

  • Ambien/Ambien CR (zolpidem, Sanofi Aventis)
  • Butisol Sodium (butabarital, Medpointe Pharm HLC)
  • Carbrital (pentobarbital and carbroma, Parke-Davis)
  • Dalmane (flurazepam, Valeant Pharm)
  • Doral (quazepam, Questcor Pharms)
  • Halcion (triazolam, Pharmacia & Upjohn)
  • Lunesta (eszopiclone, Sepracor)
  • Placidyl (ethchlorvynol, Abbott)
  • Prosom (estazolam, Abbott)
  • Restoril (temazepam, Tyco Healthcare)
  • Rozerem (ramelteon, Takeda)
  • Seconal (secobarbital, Lilly)
  • Sonata (zaleplon, King Pharmaceuticals)