The FDA’s recent recommendation that the bedtime dose be lowered came about because new data show that blood levels may be high enough the morning after use to impair activities that require alertness.
The FDA’s recent recommendation that the bedtime dose of zolpidem, a widely prescribed insomnia drug, be lowered came about because new data show that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving.
The FDA focused on certain zolpidem products approved for bedtime use and marketed as generics but also reminded the public that all drugs taken for insomnia can impair driving and activities that require alertness the morning after use.
The FDA provided an overview of this issue with the following questions and answers:
Q:What is zolpidem?
A: Zolpidem, a sedative-hypnotic medicine used in adults for managing insomnia, is available as an oral tablet (Ambien and generics), an extended-release tablet (Ambien CR and generics), a sublingual (under-the-tongue) tablet (Edluar), and an oral spray (Zolpimist). Zolpidem also is available under the brand name Intermezzo, a lower dose sublingual tablet.
Q:Why is the FDA requiring the manufacturers of certain zolpidem-containing products to revise the labeling to lower the recommended dose of zolpidem for women and to recommend consideration of the lower dose in men?
A: Next-morning blood levels of zolpidem may be high enough to impair activities that require alertness, including driving. Patients with high levels of zolpidem may be impaired even if they feel fully awake. Because zolpidem is eliminated from the body more slowly in women, the drug can stay in their systems longer.
Q:What should patients currently taking the 10 mg or 12.5 mg dose of zolpidem-containing insomnia medicines do now?
A: They should continue taking their prescribed dose as directed until they have contacted their health care professional to ask for instructions on how to safely continue to take the medicine.
Q:Will a lower dose of zolpidem be effective in managing insomnia?
A: The FDA has informed the manufacturers that the recommended dose of zolpidem for women should be lowered from 10 mg to 5 mg for immediate-release products and from 12.5 mg to 6.25 mg for extended-release products. For men, the FDA has informed the manufacturers that the labeling should recommend that health care professionals consider prescribing these lower doses, which will be effective in most women and many men.
Q:Is the FDA requiring the manufacturer of Intermezzo sublingual tablets to also change the dosing recommendations?
A: No. When Intermezzo was FDA-approved, the label already recommended a lower dosage in women compared with men.
Q:Do any other factors, such as a patient’s age, weight, or ethnicity, have an effect on zolpidem levels?
A: No relationship was evident between the zolpidem blood level and patients’ body weight or ethnicity in data from pharmacokinetic trials. Zolpidem blood levels may be higher in older patients and the lower doses are already recommended. In contrast to younger patients, zolpidem blood levels in older patients are not affected by gender.
Q:Why is the FDA informing the public about this safety risk now, after zolpidem has been on the market for nearly 20 years?
A: The FDA has been continually monitoring zolpidem’s safety profile since its approval. Over the years, the FDA has received reports of possible driving impairment and motor vehicle accidents associated with zolpidem; in most cases, however, determining whether the driving impairment was related to zolpidem or to specific zolpidem blood levels was difficult because information about time of dosing and time of the impairment often was not reported. Recently, data from clinical trials and driving simulation studies allowed the FDA to better characterize the risk of driving impairment caused by specific blood levels of zolpidem and to recognize the increased risk of driving-impairing blood levels of zolpidem in women, resulting in the requirement that the manufacturers of certain zolpidem-containing products revise the dosing recommendations.
Q:Is next-morning impairment the same as complex sleep-related behaviors?
A: Next-morning impairment occurs when patients are awake the next morning but levels of the insomnia medicine in their blood remain high enough to impair activities that require alertness, including driving. Complex sleep-related behaviors occur when patients get out of bed while not fully awake and sleep walk or perform an activity, such as drive a car or prepare and eat food. Both problems are worsened by high levels of zolpidem.
Q:Is the FDA requiring the manufacturers of other insomnia medicines to revise their dosing recommendations?
A: Currently, only the manufacturers of certain zolpidem-containing products are being required to revise their dosing recommendations.
Q:Do other insomnia medicines have the same gender effect as zolpidem?
A: The FDA currently is evaluating other insomnia medicines to determine whether they affect men and women differently.
Q:Do over-the-counter insomnia medicines that are available without a prescription have a risk of next-morning impairment?
A: Yes. The FDA is not recommending that patients who currently are taking prescription insomnia medicines switch to over-the-counter insomnia medicines. Patients who drive or perform activities that require full alertness the next morning should discuss with their health care professional whether the insomnia medicine they are using is right for them.
Q:What can patients do to decrease their risk of next-morning impairment with insomnia medicines?
A: They can take the lowest dose of their insomnia medicine that manages their symptoms and take their insomnia medicine exactly as prescribed. Taking a higher dose than prescribed or using more than one insomnia medicine is dangerous if patients drive or perform activities that require full alertness the next morning, even if the drugs are taken at the beginning of the night.
The FDA urges health care professionals to caution all patients who use these zolpidem products about the risks of next-morning impairment for activities that require complete mental alertness, including driving.