FDA Drug Safety Podcast: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem

Narrator:Welcome to the FDA Drug Safety Podcast for Healthcare Professionals from the Division of Drug Information. Today’s topic: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem.

U.S. Public Health Service Pharmacist LCDR Jennifer Shepherd in the Division will provide you with additional information about this Communication.

Guest Speaker: On January 10, 2013, the Food and Drug Administration issued a Drug Safety Communication notifying the public of new information about zolpidem. FDA recommends that the bedtime dose be lowered 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. This announcement focuses on zolpidem products approved for bedtime use, which are marketed as generics and under the brand names Ambien, Ambien CR, Edluar, and Zolpimist.

FDA is also reminding the public that all drugs taken for insomnia can impair driving and activities that require alertness the morning after use. Drowsiness is already listed as a common side effect in the drug labels of all insomnia drugs, along with warnings that patients may still feel drowsy the day after taking these products. Patients who take insomnia drugs can experience impairment of mental alertness the morning after use, even if they feel fully awake.

FDA urges healthcare 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. For zolpidem products, data show the risk for next-morning impairment is highest for patients taking the extended-release forms of these drugs (marketed as Ambien CR and generics). Women appear to be more susceptible to this risk because they eliminate zolpidem from their bodies more slowly than men.

Because use of lower doses of zolpidem will result in lower blood levels in the morning, FDA is requiring manufacturers of Ambien, Ambien CR, Edluar, and Zolpimist to lower the recommended dose. 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. FDA also informed the manufacturers that, for men, the labeling should recommend that healthcare professionals consider prescribing the lower doses―5 mg for immediate-release products and 6.25 mg for extended-release products.

The recommended doses of Intermezzo, a lower dose zolpidem product approved for middle-of-the-night awakenings, are not changing. At the time of Intermezzo’s approval, the label already recommended a lower dosage for women than for men.

FDA is continuing to evaluate the risk of impaired mental alertness with other insomnia drugs, including over-the-counter drugs available without a prescription.

To decrease the potential risk of impairment with all insomnia drugs, healthcare professionals should prescribe, and patients should take, the lowest dose capable of treating the patient’s insomnia. Patients who drive or whose activities require full alertness the morning after use of an insomnia drug should discuss the appropriateness of their medicine with their healthcare professional.

A summary of the FDA requirements for manufacturers of zolpidem products follows:

• FDA is requiring the manufacturers of certain immediate-release zolpidem products (Ambien, Edluar, and Zolpimist) to lower the recommended dose. FDA has informed manufacturers of these products that:

• The recommended initial dose for women should be lowered from 10 mg to 5 mg, immediately before bedtime.
• The drug labeling should recommend that healthcare professionals consider prescribing a lower dose of 5 mg for men. In many men, the 5 mg dose provides sufficient efficacy.
• The drug labeling should include a statement that, for both men and women, the 5 mg dose could be increased to 10 mg if needed, but the higher dose is more likely to impair next-morning driving and other activities that require full alertness.

• FDA is also requiring the manufacturer of extended-release zolpidem (Ambien CR) to lower the recommended dose. FDA has informed the manufacturer that:

• The recommended initial dose for women should be lowered from 12.5 mg to 6.25 mg, immediately before bedtime.
• The drug labeling should recommend that healthcare professionals consider prescribing a lower dose of 6.25 mg in men. In many men, the 6.25 mg dose provides sufficient efficacy.
• The drug labeling should include a statement that, for both men and women, the 6.25 mg dose can be increased to 12.5 mg if needed, but the higher dose is more likely to impair next-morning driving and other activities that require full alertness.

At this time FDA recommends that Healthcare Professionals be aware of the following:

• Recommended zolpidem doses for women and men are different because women eliminate zolpidem from their bodies at a slower rate than men.
• For zolpidem and other insomnia drugs, the lowest dose that treats the patient’s symptoms should be prescribed.
• All patients who use these products should be cautioned about the risks of next-morning impairment for activities that require complete mental alertness, including driving.
• Impairment from sleep drugs can be present despite feeling fully awake.
• Patients should be encouraged to read the Medication Guide when they receive their zolpidem prescription.
• And adverse events involving zolpidem or other insomnia drugs should be reported to the FDA MedWatch program at www.fda.gov/medwatch. 

Narrator: Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. A link to this communication as well as the complete Data Summary can be found at www.fda.gov/DrugSafetyCommunications. If you have drug questions, you can reach us at druginfo@fda.hhs.gov.

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