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

From the Guidelines

Eszopiclone should be prescribed at the lowest effective dose and for the shortest possible duration to minimize the incidence of adverse events, such as serious injuries caused by sleep behaviors, as recommended by the U.S. Food and Drug Administration 1. Eszopiclone is a non-benzodiazepine sedative-hypnotic medication primarily used for the treatment of insomnia.

• It's typically prescribed at doses of 1-3 mg taken orally at bedtime, with 1 mg recommended for elderly patients or those with hepatic impairment.
• The medication works by enhancing the activity of GABA, an inhibitory neurotransmitter in the brain, which helps induce sleep.
• Patients should take eszopiclone immediately before bedtime and ensure they have at least 7-8 hours available for sleep to avoid next-day impairment.
• Common side effects include unpleasant taste, headache, dizziness, and morning drowsiness.
• Eszopiclone is generally recommended for short-term use (2-4 weeks) due to potential for dependence, though some patients may use it for longer periods under medical supervision, as benefits seemed to outweigh potential harms, according to a systematic review that included 17 RCTs studying the efficacy of different formulations, doses, and frequency of administration of 4 nonbenzodiazepine BZRAs, including eszopiclone 1.
• Patients should avoid alcohol while taking this medication and should not abruptly discontinue use after extended treatment as withdrawal symptoms may occur.
• If insomnia persists beyond a few weeks of treatment, patients should consult their healthcare provider to evaluate for underlying conditions contributing to sleep difficulties, as the work group advised against use of benzodiazepines or trazodone for treatment of chronic insomnia disorder, due to the widely known harms and adverse effects of benzodiazepines, including risk for dependency and diversion, falls and cognitive impairment in older patients, hypoventilation in patients with respiratory conditions, and neuromuscular diseases 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY SECTION 12. 1 Mechanism of Action 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 nonbenzodiazepine hypnotic that is a pyrrolopyrazine derivative of the cyclopyrrolone class with a chemical structure unrelated to pyrazolopyrimidines, imidazopyridines, benzodiazepines, barbiturates, or other drugs with known hypnotic properties.

The mechanism of action of eszopiclone is believed to result from its interaction with GABA-receptor complexes.

• The precise mechanism is unknown.
• Eszopiclone is a nonbenzodiazepine hypnotic.
• It has a chemical structure unrelated to other drugs with known hypnotic properties 2.

From the Research

Overview of Eszopiclone

• Eszopiclone is a nonbenzodiazepine hypnotic agent used for the treatment of insomnia in adults 3, 4, 5, 6, 7.
• It is the S-isomer of racemic zopiclone and 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, and a mean elimination half-life of 6 hours 3.
• The half-life increases with age, 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, but patients with severe hepatic insufficiency should have a reduced dose 3.

Efficacy and Safety

• Eszopiclone has been shown to significantly improve sleep onset and maintenance, reduce sleep onset latency, and increase total sleep time in adults with primary insomnia 3, 4, 5, 6, 7.
• The drug is generally well tolerated, with common side effects including unpleasant taste, headache, dry mouth, and dizziness 3, 4, 5, 6, 7.
• There is no evidence of tolerance during 12 months of treatment with eszopiclone, and no significant rebound insomnia or withdrawal effects have been reported 3, 4, 6.

Clinical Use

• Eszopiclone is approved for the treatment of insomnia in adults, including those with difficulty falling asleep and those with difficulty staying asleep 3, 4, 5, 6, 7.
• The recommended starting dosage is 2 mg immediately before bedtime, with adjustment to 3 mg if clinically indicated, and dosage adjustment is necessary in patients with severe hepatic disease 3, 5.
• Eszopiclone has been shown to be effective in both non-elderly and elderly patients, and in patients with co-morbid insomnia 4, 6, 7.