What is Eszopiclone (Lunesta, a non-benzodiazepine hypnotic agent)?

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From the Guidelines

Eszopiclone (brand name Lunesta) is a non-benzodiazepine sedative-hypnotic medication primarily used for treating insomnia, with a typical starting dose of 1 mg taken immediately before bedtime, and it can be increased to 2-3 mg if needed, with elderly patients generally starting at lower doses (1 mg) 1.

Key Points

  • Eszopiclone works by enhancing the activity of GABA, an inhibitory neurotransmitter in the brain that promotes sleep, helping patients fall asleep faster and stay asleep longer, with effects typically lasting 6-8 hours 1.
  • Common side effects include unpleasant taste, headache, dizziness, and morning drowsiness 1.
  • Patients should take eszopiclone only when they have 7-8 hours available for sleep to avoid next-day impairment, and it's generally recommended for short-term use (2-4 weeks), though some patients may use it for longer periods under medical supervision 1.
  • Patients should avoid alcohol while taking eszopiclone as it can dangerously increase sedation effects, and abrupt discontinuation after prolonged use may cause withdrawal symptoms, so tapering is often recommended 1.

Considerations

  • The U.S. Food and Drug Administration recently released a safety announcement on the risk for serious injuries caused by sleep behaviors (sleepwalking, sleep driving, and other activities while not fully awake) associated with nonbenzodiazepine BZRAs, including eszopiclone 1.
  • To minimize the incidence of adverse events, eszopiclone should be administered at the lowest effective dose and for the shortest possible duration, and all patients offered this agent should be counseled on the potential risks 1.
  • Nonpharmacologic behavioral interventions, such as cognitive-behavioral therapy for insomnia (CBT-I), are considered more effective than pharmacologic therapies for treatment of chronic insomnia disorder, but eszopiclone may be considered for patients who are unable or unwilling to receive CBT-I 1.

From the FDA Drug Label

Eszopiclone is a nonbenzodiazepine hypnotic agent that is a pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is believed to result from its interaction with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors Eszopiclone is a white to light-yellow crystalline solid. Eszopiclone has a single chiral center with an (S)-configuration.

Eszopiclone (Lunesta) is a non-benzodiazepine hypnotic agent. It is a pyrrolopyrazine derivative of the cyclopyrrolone class. The mechanism of action is not fully understood, but it is believed to interact with GABA-receptor complexes. 2 2

From the Research

Definition and Mechanism of Action

  • Eszopiclone, also known as Lunesta, is a non-benzodiazepine hypnotic agent used for the treatment of insomnia 3, 4, 5, 6, 7.
  • It is the S-isomer of racemic zopiclone, a cyclopyrrolone with sedative-hypnotic activity 3, 5.
  • Eszopiclone acts by binding to the GABA(A) receptor, with more selectivity for certain subunits compared to benzodiazepine hypnotics 3.

Pharmacokinetics and Pharmacodynamics

  • Eszopiclone is rapidly absorbed after oral administration, with peak plasma concentrations attained 1.0-1.6 hours after a 3 mg dose 3.
  • The mean elimination half-life is 6 hours, increasing to about 9.0 hours in patients 65 years or older 3.
  • Eszopiclone's pharmacokinetic profile is not substantially modified in patients with renal failure or mild-to-moderate hepatic impairment 3.

Efficacy and Safety

  • Eszopiclone has been shown to significantly improve sleep onset and maintenance, as well as reduce sleep onset latency, number of awakenings, and wake time after sleep onset 3, 4, 6, 7.
  • It has also been found to improve daytime functioning and health-related quality of life in patients with primary insomnia 4, 6, 7.
  • Common side effects include unpleasant or bitter taste, headache, dyspepsia, pain, diarrhea, dry mouth, and dizziness 3, 5, 6.
  • Eszopiclone has been found to be generally well tolerated, with no evidence of tolerance during 12 months of treatment and no rebound insomnia or serious withdrawal effects upon discontinuation 4, 6, 7.

Clinical Use

  • Eszopiclone is approved for the treatment of insomnia in adults, including those with difficulty falling asleep and those with difficulty staying asleep 4, 6, 7.
  • It is also used for the treatment of co-morbid insomnia, where insomnia coexists with other conditions that disturb sleep 4, 7.
  • The recommended starting dosage is 2 mg immediately before bedtime, with adjustment to 3 mg if clinically indicated 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Eszopiclone: its use in the treatment of insomnia.

Neuropsychiatric disease and treatment, 2007

Research

Eszopiclone.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2006

Research

Eszopiclone for the treatment of insomnia.

Expert opinion on pharmacotherapy, 2006

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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