Lower doses for certain zolpidem-containing drugs

Abstract

In January 2013, FDA alerted health professionals of the risk of nextmorning impairment after use of insomnia drugs containing zolpidem (http://apha.us/XP5ngM). FDA recommended lowering the bedtime dose of Ambien and Ambien CR (Sanofi), Edluar (Meda), and Zolpimist (NovaDel) because of new data showing that in some patients, the drugs may impair activities requiring alertness, including driving, the next morning. In January 2013, FDA alerted health professionals of the risk of nextmorning impairment after use of insomnia drugs containing zolpidem (http://apha.us/XP5ngM). FDA recommended lowering the bedtime dose of Ambien and Ambien CR (Sanofi), Edluar (Meda), and Zolpimist (NovaDel) because of new data showing that in some patients, the drugs may impair activities requiring alertness, including driving, the next morning. FDA urged health professionals to caution all patients who use Zolpidem products about the risks of next-morning impairment for activities that require mental alertness, including driving. The risk is highest for patients taking extended-release forms (Ambien CR and generics). Women appear to be more susceptible because they eliminate Zolpidem from their bodies more slowly.■FDA required manufacturers to lower the recommended dose of zolpidem products because of risk of next morning impairment.■Women are more susceptible to drowsiness than men. ■FDA required manufacturers to lower the recommended dose of zolpidem products because of risk of next morning impairment.■Women are more susceptible to drowsiness than men. Because lower doses result in lower morning blood levels, FDA required Sanofi, Meda, and NovaDel to lower their recommended doses. For women, the dose was lowered from 10 mg to 5 mg for immediate-release products (Ambien, Edluar, and Zolpimist) and from 12.5 mg to 6.25 mg for extended-release products (Ambien CR). Both lower doses are also recommended for men. Intermezzo, a Zolpidem product approved in November 2011 for middle-of-the-night awakenings, already recommended a lower dosage for women (http://apha.us/Ya4SQE). Drugs for insomnia can impair driving and activities that require alertness the morning after use. Drowsiness is already listed in the labeling as a common adverse effect, along with warnings that patients may feel drowsy the next day. According to driving simulation and laboratory studies recently submitted to FDA, Zolpidem blood levels above about 50 ng/mL appear capable of impairing driving and increasing the risk of a motor vehicle accident. In pharmacokinetic trials of Ambien 10 mg (or equivalent) including approximately 250 men and 250 women, about 15% of women and 3% of men had Zolpidem concentrations exceeding 50 ng/mL approximately 8 hours postdose. Three women and one man had Zolpidem concentrations of at least 90 ng/mL about 8 hours after use. More male and female patients experienced potentially impairing morning Zolpidem levels after use of extended-release products. In pharmacokinetic trials of extended-release Zolpidem 12.5 mg, approximately 33% of women and 25% of men had Zolpidem blood concentrations exceeding 50 ng/mL approximately 8 hours postdose. About 5% of patients had concentrations of at least 100 ng/mL. In studies of extended-release Zolpidem 6.25 mg, at 8 hours after dosing, about 15% of adult women and 5% of adult men had a Zolpidem blood concentration of at least 50 ng/mL, whereas in elderly men and women, about 10% had a concentration that high. FDA will continue to evaluate the risk of next-morning impairment with insomnia drugs.Table 1Zolpidem dosing recommendations for nonelderly adultsDosing recommendations in current drug label for zolpidemFDA's proposed new dosing recommendations for zolpidemAmbien, Edluar, ZolpimistMen and women: 10 mg once daily, immediately before bedtimeWomen: 5 mg once daily, immediately before bedtime Men: 5 mg or 10 mg once daily, immediately before bedtimeAmbien CRMen and women: 12.5 mg once daily, immediately before bedtimeWomen: 6.25 mg once daily, immediately before bedtime Men: 6.25 mg or 12.5 mg once daily, immediately before bedtime Open table in a new tab Following are points to consider when providing guidance to physicians or counseling patients or their caregivers.■Recommend the lowest doses of Zolpidem or other insomnia drugs.■Extended-release Zolpidem may not be the right choice for those who need full alertness the next morning.■Caution all patients who fill prescriptions for these products about the risks of next-morning impairment for activities that require alertness, including driving.■OTC insomnia medicines should not be considered safer than prescription insomnia medicines for next-morning alertness and driving.■The recommended Zolpidem doses for women and men are different because women eliminate Zolpidem from their bodies more slowly.■Patients may be impaired from sleep drugs even if they feel fully awake.■Encourage patients to read the Medication Guide when they receive their Zolpidem prescription.■Pharmacists and patients should report adverse events to FDA Med- Watch (www.fda.gov/medwatch).