Pharmacology Update

Eszopiclone Tablets (LunestaTM)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD

A new nonbenzodiazepine hypnotic has been approved by the FDA for the treatment of insomnia. Eszopiclone is the active (S)-isomer of zopiclone that is available outside of the United States. It shares pharmacological characteristics with other nonbenzodiazepine agents such as zolpidem and zaleplon. Eszopiclone is marketed by Sepracor as LunestaTM.

Indications

Eszopiclone is indicated for the treatment of insomnia.1

Dosage

The recommended starting dose is 2 mg immediately before bedtime for those with difficulty in falling asleep. The dose may be increased to 3 mg for sleep maintenance. For elderly patients the recommended dose is 1 mg and 2 mg respectively.1

Eszopiclone is available as 1 mg, 2 mg, and 3 mg tablets.

Potential Advantages

Zolpiclone appears to have greater anxiolytic activity than zolpidem or zaleplon.2 Eszopiclone may provide better relief of anxiety with less sedation compared to zopiclone.3,4 Unlike zolpidem or zaleplon, eszopiclone is not limited to short-term use by FDA-approved labeling.

Potential Disadvantages

Eszopiclone has an elimination half-life of approximately 6 hours. It may be less effective in reducing sleep latency than agents with shorter half-lives (eg, zaleplon), and it may be more likely to have residual next day effects.5 The racemic form of zopiclone has been associated with residual effects on driving, divided attention, and memory compared to zaleplon and more rebound on discontinuation than zolpidem.6,7 Most common adverse events associated with eszopiclone are headache (17-21% vs 13% for placebo) and unpleasant taste (17-34% vs 3%).1

Comments

Eszopiclone is the pure (S)-isomer of zopiclone one of the 3 nonbenzodiazepine hypnosedatives. They offer some advantages over benzodiazepines in terms of tolerance, dependence, and withdrawal.2 In a randomized, double-blind, placebo-controlled study eszopiclone significantly improved sleep latency, wake time after sleep onset, number of awakenings, sleep time, and quality of sleep compared to placebo.8 No evidence of tolerance was reported. After 6-weeks of use, discontinuation-emergent effect appeared to be mild and, while sleep efficiency was reduced, it appeared to be resolved by the second night after discontinuation.1 There are currently no published comparative trials with other nonbenzodiazepine agents as comparative trials have been with the racemic form. Zopiclone is associated with more cognitive and memory affect than zaleplon and with more withdrawal effects than zaleplon and zolpidem.9 The group has a whole has been associated with a low incidence of dependence compared to benzodiazepine.10

The wholesale cost of eszopiclone ranges from $2.80 to $3 per day and is about 50 cents to $1 higher than zolpidem or zaleplon.

Clinical Implications

Eszopiclone does not appear to offer any clear clinical advantages over available nonbenzodiazepine drugs such as zaleplon and zolpidem.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Lunesta Product Information. Sepracor Inc. December 2004.

2. Drover DR. Clin Pharmacokinet. 2004;43(4):227-238.

3. Carlson JN, et al. Eur J Pharmacol. 2001;415(2-3): 181-189.

4. Georgiev V. Curr Opin Investig Drugs. 2001;2:271-273.

5. Nakajima T, et al. Psychiatry Clin Neurosci. 2000; 54(1):37-40.

6. Vermeeren A, et al. Sleep. 2002;15:25(2):224-231.

7. Tsutusi S, et al. J Int Med Res. 2001;29(3):163-177.

8. Krystal AD, et al. Sleep. 2003;26(7):793-799.

9. Terzano MG, et al. Drug Safety. 2003;26(4):261-282.

10. Hajak G, et al. Addiction. 2003;98(10):1371-1378.