Eszopiclone
(LunestaTM)
Classification:
non-benzodiazepine sedative hypnotic
Pharmacology:
The sedative-hypnotic properties of eszopiclone are thought to be a result of modulation at
the GABAA receptor chloride channel complex. The primary site of activity is at the alpha
subunit, which is also known as the benzodiazepine or omega receptor. Three subtypes of
the omega receptor have been identified; and like benzodiazepines, eszopiclone binds nonselectively to all three receptors. Because of this, eszopiclone provides a sedative effect
similar to that of benzodiazepines.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract; absorption delayed by high-fat meals
Peak plasma concentrations reached within one hour of a single oral dose
Distribution: 52-59% protein bound
Metabolism: Hepatic oxidation and demethylation occur through CYP3A4 and 2E1. Two
metabolites are produced; one with diminished activity compared to
eszopiclone, the other having no activity.
Elimination: Elimination t1/2 ~6 hours
Urinary elimination: 75% excreted as metabolites, <10% excreted unchanged
Indication:
Hypnotic agent for the treatment of chronic or transient insomnia
Dosage and Administration:
Initial dose: 2mg immediately before bedtime, may be titrated to a maximum dose of 3mg
Elderly patients: difficulty falling asleep: 1mg, may be titrated to 2mg
difficulty staying asleep: 2mg
Severe hepatic impairment: 1mg
Administration of eszopiclone with or immediately after a high-fat meal is not recommended,
as this has been shown to substantially delay Tmax.
Contraindications:
There are no known contraindications.
Precautions:

Pregnancy category C

Known hypersensitivity to this product or any ingredient in this product

Respiratory diseases, such as COPD or sleep apnea

Significant hepatic impairment; dosage adjustment required if severe

Elderly/debilitated patients; dosage adjustment required

Symptoms of depression or suicidal ideation

Concomitant use of CNS depressants

Concomitant use of potent 3A4 inhibitors

Avoid driving/operating heavy machinery following administration

Activities following administration should be limited to those necessary to prepare for bed

Abrupt discontinuation may lead to withdrawal symptoms
Interactions:
Eszopiclone is a substrate of 3A4 (major) and 2E1 (minor). Inhibitors of CYP3A4 (i.e.
ciprofloxacin, clarithromycin, doxycycline, erythromycin, fluoxetine, fluvoxamine, isoniazid,
protease inhibitors, verapamil) can significantly increase the levels and effects of
eszopiclone. Likewise, inducers of CYP3A4 (i.e. carbamazepine, phenobarbital, phenytoin)
can decrease the levels and effects of eszopiclone.
Concomitant use of ethanol or other CNS depressants can increase the risk of sedation.
Adverse Reactions:
Sleep related behaviors such as sleep-driving, sleep-walking, eating while sleeping, or
making phone calls while sleeping may possibly be experienced while taking eszopiclone.
Other side effects include headache, unpleasant taste, somnolence, dizziness,
nervousness, depression, hallucinations, rash, and xerostomia.
Cost comparison of sedative-hypnotics:
Generic Name
Brand Name
eszopiclone
Lunesta®
zaleplon
Sonata®
zolpidem
Ambien®
Strength
1, 2, 3mg
5mg
5mg
Unit Price
$4.09
$2.67
$0.05
Shape
Round tablet
Round tablet
Round tablet
Imprint
S190
S191
S193
Monitoring Parameters:
No standard monitoring is required.
Product Identification:
Dose
1mg
2mg
3mg
Color
Light blue
White
Dark blue
Efficacy:
The efficacy of eszopiclone in reducing sleep latency and improving sleep maintenance
was established in six placebo controlled studies involving 2100 patients with chronic and
transient insomnia.
Chronic insomnia: Five controlled trials studied the effectiveness of eszopiclone on chronic
insomnia; three studies in adult subjects, and two in elderly subjects.
 Adults with chronic insomnia were studied in a 6-week double-blind trial comparing
eszopiclone 2mg and 3mg with placebo. Overall, both the 2mg and 3mg
eszopiclone were superior to placebo.
 Adults with chronic insomnia were evaluated for safety and efficacy of eszopiclone
3mg compared to placebo in a 6 month double-blind trial. Eszopiclone was shown to
be superior to placebo using subjective measures.
 Adults with chronic insomnia were studied in a 6 period cross-over polysomnograph
trial comparing eszopiclone doses of 1 to 3mg. Response was shown to be dose
related.
 Elderly subjects with chronic insomnia were evaluated in 2 double-blind trials lasting
2 weeks, comparing eszopiclone 1 and 2 mg to placebo. Both studies showed
eszopiclone to be superior to placebo.
Transient insomnia: Healthy adults with transient insomnia were evaluated in a double-blind
single-night trial comparing eszopiclone to placebo. Eszopiclone was superior to placebo
on all measures of sleep latency and maintenance.
Conclusions:
Eszopiclone has been shown to be effective in reducing sleep latency and improving sleep
maintenance in both chronic and transient insomnia. Despite the added benefit of approval
for long-term use, the cost-effectiveness of eszopiclone remains unclear without head-tohead clinical trials comparing the efficacy of eszopiclone to the other sedative-hypnotic
agents available. In addition, other less costly agents, such as zolpidem, have also
demonstrated efficacy and tolerability on a long-term basis in clinical trials.
Recommendation:
Addition to the formulary is not recommended.
References:
1. Amato DA, Caron J, Krystal AD, Roach J, Roth T, Rubens R, et al. Nightly treatment of
primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and
work limitations. Sleep 2007; 30(8):959-68.
2. Amato DA, Erman M, McCall W, Rosenberg R, Seiden D, Scharf M, et al. A 2-week
efficacy and safety study of eszopiclone in elderly patients with primary insomnia. Sleep
2005; 28(6):720-7.
3. Erman M, Krystal AD, McCall W, Rosenberg R, Scharf M, Wessel T, et al. A
polysomnography study of eszopiclone in elderly patients with insomnia. Current
Medical Research and Opinion 2006; 22(9):1633-42.
4. Erman M, Krystal AD, Roth T, Soubrane MD, Zammit GK. Long-term efficacy and
safety of zolpidem extended release 12.5 mg, administered 3 to 7 nights per week for
24 Weeks, in patients with chronic primary insomnia: a 6-month, randomized, doubleblind, placebo-controlled, parallel-group, multicenter study. Sleep 2008; 31(1):71-90.
5. Krystal AD, Roehrs T, Roth T, Walsh J, Wessel T. An evaluation of the efficacy and
safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep
Medicine 2005; 6(6):487-98.
6. Krystal AD, McCall W, Perlis ML, Walsh JK. Long-term, non-nightly administration of
zolpidem in the treatment of patients with primary insomnia. Journal of Clinical
Psychiatry 2004; 65(8):1128-37.
7. LunestaTM (eszopiclone) [package insert]. Marlborough, MA: Sepracor Incorporated;
April 2006.
Prepared by:
Angela Bird
Pharmacy Volunteer
April 2008