Sanofi-Aventis' Ambien CR (zolpidem tartrate extended-release)

Carolyn Soo, PharmD, and Maryellen Dascoli
Published Online: Wednesday, February 1, 2006
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Insomnia is a disorder of initiating or maintaining sleep or of excess sleepiness that is characterized as a disturbance in the quantity, quality, or timing of sleep.1 The 1-year prevalence of insomnia is estimated to be between 30% and 40% of all adults. It is greater among the elderly.1

Current pharmacologic treatments include benzodiazepines (BZDs), tricyclic antidepressants, antihis-tamines, and selective BZD receptor agonists, including zolpidem. Since the addition of zolpidem in 1993, it has become one of the more commonly prescribed sleep medications. In September 2005, Sanofi- Aventis announced FDA approval of its extended-release formulation of zolpidem, Ambien CR.2

Pharmacology

Zolpidem, an imidazopyridine, is a sedative-hypnotic that alters GABA activity by selectively binding to BZD1 receptors in the brain. Because of its selectivity, it has more predominant hypnotic effects and less anxiolytic, anticonvulsant, and myorelaxant effects than nonselective BZDs.3

Ambien CR is a 2-layer tablet, with the first layer releasing drug immediately and the second allowing a slower release of drug. The mean elimination half-life is 2.8 hours.4

Clinical Trials

Two randomized, controlled trials were conducted to evaluate the use of extended-release zolpidem in patients with primary insomnia. One study evaluated 212 adults in a double-blind, randomized, parallel-group, placebo-controlled, 3-week trial of Ambien CR 12.5 mg. The study found Ambien CR to decrease wake after sleep onset (WASO) for the first 7 hours during the initial 2 nights of sleep and for the first 5 hours after 2 weeks of treatment. Polysomnography recordings showed superiority over placebo in decreasing latency to persistent sleep on the first 2 nights of treatment and after 2 weeks.4

The second study evaluated Ambien CR in 205 elderly participants over the age of 65 with primary insomnia. The trial design was similar to that of the first trial, although the dose of Ambien CR was reduced to 6.25 mg. A decreased WASO also was observed for the first 7 hours during the initial 2 nights and for the first 5 hours after 2 weeks. Ambien CR was superior to placebo in decreasing latency to persistent sleep on the first 2 nights of treatment and after 2 weeks.4

Safety

The safety of Ambien CR is expected to be comparable to that of the immediate-release formulation. The most common adverse events associated with zolpidem include central nervous system (CNS) effects such as nausea, dizziness, and drowsiness.3 Because elderly patients may have impaired motor and/or cognitive performance, it is recommended that the dose for them be reduced to 6.25 mg.4

Ambien CR is a schedule IV medication, and it is in pregnancy category C. There is limited evidence of any significant drug interactions with zolpidem. Precaution should be taken, however, if it is used concomitantly with other CNS depressants.

Outlook

Ambien CR has been shown to be safe and effective for both sleep induction and sleep maintenance. Ambien CR may be favorable, compared with other sleep medications, because of its tolerability and its side-effect profile.

The recommended dose is 12.5 mg for adults and 6.25 mg for elderly patients. Ambien CR should be taken close to bedtime because of its rapid onset, although the onset may be prolonged if it is taken with food.4

Dr. Soo is a senior research pharmacist with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Ms. Dascoli is a sixth-year PharmD candidate from Northeastern University, currently on clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.




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