Eszopiclone is a benzodiazepine receptor agonist that is used for the treatment of insomnia. Eszopiclone has not been implicated in causing serum enzyme elevations or clinically apparent liver injury.


Eszopiclone (es zoe' pi klone) is a non-benzodiazepine, benzodiazepine receptor agonist of the cyclopyrrolone class that acts by binding to the benzodiazepine (BZ) site on the GABA receptor complex, causing neural inhibition and helping to induce sleep. Eszopiclone has selectivity for certain BZ receptor subtypes, and does not have the neuromuscular relaxation or anticonvulsant effects of the standard benzodiazepines. Eszopiclone has a relatively short half life and rapid onset of action. In multiple placebo controlled trials, eszopiclone was shown to decrease the latency to onset of sleep and improve perceived sleep quality, with few next day residual effects and minimal evidence of rebound insomnia after withdrawal. Eszopiclone is the S-isomer of zopiclone that has been available in other countries for more than 20 years. Eszopiclone was approved for use in the United States in 2004 for the treatment of insomnia and remains in common use. Eszopiclone is available in 1, 2 and 3 mg tablets generically and under the brand name Lunesta. The recommended dose is 1 to 3 mg taken orally immediately before bedtime. Like the other benzodiazepine receptor agonists, eszopiclone is classified as a Schedule IV controlled substance (low potential for abuse and limited physical or psychological dependence). Side effects are uncommon, usually mild and may include unpleasant taste (bitter), headache, nausea, dizziness, dry mouth and drowsiness.


In multiple premarketing randomized controlled trials, eszopiclone was not associated with an increased rate of serum enzyme elevations in comparison to placebo therapy, and no instance of clinically apparent liver injury was reported. Since its approval and widescale use, eszopiclone has not been implicated in causing clinically apparent liver disease, although hepatitis and liver injury are listed as a rare adverse reactions in the product label. Eszopiclone is metabolized in the liver by the cytochrome P450 system (predominantly CYP 3A4 and 2E1). Nevertheless, drug-drug interactions appear to be uncommon. Thus, eszopiclone induced liver injury must be rare, if it occurs at all.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Drug Class: Sedatives and Hypnotics

Other Drugs in the Subclass, Benzodiazepine Receptor Agonists: Zaleplon, Zolpidem



Eszopiclone – Generic, Lunesta®


Sedatives and Hypnotics


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 20 February 2018

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    (45 year old woman found to have minor serum ALT elevations [1.5-3 times ULN] without jaundice or symptoms while taking zolpidem, which improved on stopping, but which were subsequently shown to be due to severe sleep apnea).
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    (Controlled trial of 44 days of two doses of eszopiclone vs placebo in 308 patients with insomnia; adverse events were uncommon, but included headache, dry mouth and drowsiness; "there was no evidence of drug-related effects on...laboratory...measures").
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    (Controlled trial of 4 doses of eszopiclone vs placebo given for one night in 436 patients; most common side effect was unpleasant taste and changes in laboratory test results "were similar across all treatment groups, including placebo").
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    (Controlled trial of 12 week course of eszopiclone vs placebo in 288 elderly patients with insomnia; the only adverse event that was more frequent with eszopiclone was unpleasant taste [12.4% vs 1.5%]; one treated patient developed cholecystitis which was considered unrelated to therapy).
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    (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to a sleeping aid, despite the fact that zopiclone and zolpidem are among the 25 most commonly prescribed drugs in Iceland).
  • Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]
    (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, but none were attributed to eszopiclone or other sedatives or sleeping aids).
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    (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 82 [9%] were attributed to agents active in the central nervous system, but none were due to eszopliclone or other sedatives or sleeping aids).
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