General Information

Lunesta (eszopiclone formerly referred to as Estorra) is a nonbenzodiazepine hypnotic agent approved for the long term treatment of insomnia and sleep maintenance.

Lunesta is indicated for the treatment of patients who experience difficulty falling asleep as well as for the treatment of patients who are unable to sleep through the night (sleep maintenance difficulty).

Eszopiclone was designated as a Schedule IV controlled substance in April 2005 by the Federal Register. It should not be used in conjunction with other prescription or nonprescription sleep aids, by pregnant women, or by patients with known psychiatric illness without medical supervision. Patients taking eszopiclone, or any hypnotic agent, may develop dependence and experience withdrawal symptoms when discontinuing use.

The product is available in 1 mg, 2 mg, and 3 mg tablets. The recommended starting dose for Lunesta for most non-elderly adults is 2 mg immediately before bedtime. Dosing can be initiated at or raised to 3 mg if clinically indicated, since 3 mg is more effective for sleep maintenance.

For elderly patients whose primary complaint is difficulty falling asleep is 1 mg immediately before bedtime. In these patients, the dose may be increased to 2 mg if clinically indicated. For elderly patients whose primary complaint is difficulty staying asleep, the recommended dose is 2 mg immediately before bedtime.

Clinical Results

FDA approval of Lunesta was based on results from six clinical trials enrolling a total of 2100 subjects with chronic and transient insomnia. The FDA's decision to approve Lunesta for the long-term treatment of insomnia was based on a six-month, double-blind, placebo-controlled trial enrolling 788 subjects. The total NDA for Lunesta contained data from a total of 24 clinical trials.

Transient Insomnia

• In a double-blind, parallel-group, single-night trial 436 healthy adults were evaluated in a model of transient insomnia sleep laboratory in a comparing two doses of eszopiclone and placebo. Results showed that Lunesta 3 mg was superior to placebo on measures of sleep latency and sleep maintenance, including polysomnographic (PSG) parameters of latency to persistent sleep (LPS) and WASO.

Chronic Insomnia

The treatment of chronic insomnia was established in five controlled studies. Three controlled studies were in adult subjects, and two controlled studies were in elderly subjects with chronic insomnia.

• In the first study, 308 adults were evaluated in a double-blind, parallel-group trial of 6 weeks’ duration comparing Lunesta 2 mg and 3 mg with placebo. Objective endpoints were measured for 4 weeks. Clinical results showed that both 2 mg and 3 mg were superior to placebo on LPS at 4 weeks. In addition, data showed that the 3 mg dose was superior to placebo on WASO.
• In the second study, 788 adults were evaluated using subjective measures in a double-blind, parallel-group trial comparing the safety and efficacy of Lunesta 3 mg with placebo administered nightly for 6 months. Clinical results showed that Lunesta was superior to placebo on subjective measures of sleep latency, total sleep time, and WASO.
• A 6-period cross-over PSG study evaluated eszopiclone doses of 1 to 3 mg, each given over a 2-day period, demonstrated effectiveness of all doses on LPS, and of 3 mg on WASO. A dose-related response was observed in the study.

Elderly

• Elderly subjects (ages 65-86) with chronic insomnia were evaluated in two double-blind, parallel-group trials of 2 weeks’ duration. One study (n=231) compared the effects of Lunesta with placebo on subjective outcome measures, and the other (n=292) on objective and subjective outcome measures. The first study compared 1 mg and 2 mg of Lunesta with placebo, while the second study compared 2 mg of Lunesta with placebo. Results showed that all doses were superior to placebo on measures of sleep latency. In both studies, 2 mg of Lunesta was superior to placebo on measures of sleep maintenance.

Side Effects

Adverse events associated with the use of Lunesta may include (but are not limited to) the following:

• Drowsiness
• Viral Infection
• Dry Mouth
• Dizziness
• Hallucinations
• Infection
• Rash
• Unpleasant Taste

Mechanism of Action

Lunesta is a nonbenzodiazepine hypnotic agent that is a pyrrolopyrazine derivative of the cyclopyrrolone class. It is the S-isomer of the marketed non-benzodiazepine rapid-acting hypnotic zopiclone. Lunesta raises levels of an amino acid called Gamma-Aminobutyric Acid (GABA). GABA slows down brain activity so that your mind and body can relax, enabling you to fall asleep and stay sleep.

Literature References

Drug Enforcement Administration, Department of Justice. Schedules of controlled substances: placement of Zopiclone into schedule IV. Final rule. Fed Regist. 2005 Apr 4;70(63):16935-7.

Eszopiclone: Esopiclone, Estorra, S-Zopiclone, Zopiclone - Sepracor. Drugs R D. M2005; 6(2):111-115.

Rosenberg R, Caron J, Roth T, Amato D.An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults. Sleep Med. 2005 Jan;6(1):15-22. Epub 2004 Dec 25.

Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T. Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin. 2004 Dec; 20(12):1979-91.

Additional Information

For additional information regarding Lunesta or insomnia, please contact The Lunesta Web Site