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Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
Chemical Name: (5S - 6 - (5 - chloro - 2 - pyridinyl) - 6,7 - dihydro - 7 - oxo - 5H - pyrrolol[3,4 - b]pyrazin - 5 - yl - ester - 4 - methyl - 1 - piperazinecarboxylic acid
Molecular Formula: C17H17ClN6O3
CAS Number: 138729-47-2
Brands: Lunesta


Sedative and hypnotic; pyrrolopyrazine derivative; structurally unrelated to benzodiazepines.1 1 2 3 5 10 11

Uses for Eszopiclone


Management of transient and chronic insomnia.1 2 3 11

Decreases sleep latency and prolongs total sleep time in patients with chronic or transient insomnia;1 2 3 reportedly effective with repeated (i.e., nightly) use for periods up to 6 months in duration.1 2 3

Slideshow: Insomnia Treatment with Non-Benzodiazepines Ambien, Lunesta & Sonata

Sleep architecture (i.e., the percentage of time spent in each sleep stage) generally is preserved at usual dosages.5

Evidence is lacking to suggest that sleep improvement is maintained following discontinuance;13 some clinicians suggest that use of hypnotic agents in the management of chronic insomnia should be reserved for patients nonresponsive to psychotherapy/behavioral therapies (e.g., relaxation techniques, sleep hygiene education, sleep curtailment, stimulus control therapy).6 7 8

Eszopiclone Dosage and Administration


Oral Administration

Administer only immediately before retiring (when ready to sleep) or after retiring when experiencing difficulty falling asleep.1

Swallow tablets intact; do not chew, crush, or divide.1

Avoid administration with or immediately after a heavy, high-fat meal; may decrease rate of absorption and effect on sleep latency.1

Use only when able to get ≥8 hours of sleep before it is necessary to be active again.1


Individualize dosage;1 use smallest effective dosage to minimize adverse effects.1

If used concomitantly with a potent CYP3A4 inhibitor, adjustment of eszopiclone dosage is recommended.1 (See Interactions.)



Adults <65 years of age: Initially, 2 mg.1 May consider an initial dosage of 3 mg or an increase in dosage to 3 mg if clinically indicated; 3-mg dosage is more effective than 2-mg dosage for sleep maintenance.1

Special Populations

Hepatic Impairment

In patients with severe hepatic impairment, 1 mg initially;1 doses >2 mg not recommended.1

No dosage adjustment required in patients with mild to moderate hepatic impairment.1

Renal Impairment

No dosage adjustment required.1

Geriatric Patients

In adults ≥65 years of age experiencing difficulty falling asleep, 1 mg initially.1 May increase dosage to 2 mg if clinically indicated.1

In adults ≥65 years of age experiencing difficulty staying asleep, 2 mg.1

Do not exceed 2 mg daily in adults ≥65 years of age.1

Debilitated Patients

Do not exceed 1 mg.1 13

Cautions for Eszopiclone


  • None known.1



Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.1

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric and/or medical condition.1

Adverse Psychiatric Events

Abnormal thinking and behavioral changes (e.g., decreased inhibition, uncharacteristic extroversion and aggressiveness, bizarre behavior, agitation, hallucinations, depersonalization, amnesia) may occur unpredictably.1 Immediately evaluate any new behavioral sign or symptom.1

Complex Sleep-related Behaviors

Potential risk of complex sleep-related behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), making phone calls, or preparing and eating food while asleep.14

Withdrawal Effects

Rapid dosage reduction or abrupt discontinuance of sedatives or hypnotics has resulted in signs and symptoms of withdrawal.1 3

Rebound insomnia of 1 day’s duration reported in clinical trials of eszopiclone.1

Abuse Potential

Abuse potential of high doses (2–4 times recommended hypnotic dose) in individuals with a history of benzodiazepine abuse appeared to be similar to that of benzodiazepines (e.g., diazepam 20 mg).1

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.1

CNS Effects

Rapid onset of CNS effects (short-term memory impairment, hallucinations, impaired coordination, dizziness, lightheadedness); administer only immediately before going to bed or after unsuccessfully attempting to sleep.1

Performance of activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) may be impaired the day after ingestion.1

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.1 (See Specific Drugs under Interactions.)

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema; may occur as early as with the first dose of drug.14

General Precautions

Concomitant Disease

Limited experience in patients with concomitant systemic disease.1 Use with caution in patients with diseases affecting metabolism and/or hemodynamic response.1

Respiratory depression was not reported in clinical studies to date in healthy individuals receiving doses 2.5-fold higher than the recommended dose;1 however, caution is advised in patients with impaired respiratory function.1

Debilitated Patients

Potential increased sensitivity to sedatives and hypnotics or impaired motor or cognitive performance after repeated exposure.1 Reduce dosage and monitor closely.1 (See Debilitated Patients under Dosage and Administration.)


Use with caution in depressed patients.1 Potential for suicidal tendencies; overdosage more frequent in such patients.1 Prescribe and dispense drug in the smallest feasible quantity.1

Specific Populations


Category C.1


Not known whether distributed into human milk;1 however, racemic zopiclone is distributed into milk.4 Use not recommended.1 13

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Pharmacokinetic changes in geriatric patients compared with younger adults.1 (See Absorption and also Elimination, under Pharmacokinetics.)

Possibility exists of greater sensitivity to pharmacologic and adverse effects of sedatives and hypnotics in patients ≥65 years of age;1 reduce initial and maximum dosages.1 (See Geriatric Patients under Dosage and Administration.)1

The adverse effect profile of the 2-mg dosage in geriatric patients (median age: 71 years) was similar to that observed in clinical trials of the drug in younger adults.1

Hepatic Impairment

Use with caution.1 Systemic exposure increased twofold in patients with severe hepatic impairment compared with healthy individuals.1 Reduce dosage for severe hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Headache,1 3 dry mouth,1 3 dizziness,1 3 somnolence,1 nervousness,1 dyspepsia,1 nausea,1 3 infection,1 unpleasant taste.1 3

Interactions for Eszopiclone

Metabolized principally by CYP3A4 and CYP2E1.1

Does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4.1

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (increased plasma eszopiclone concentrations).1 In patients receiving a potent CYP3A4 inhibitor, initial eszopiclone dosage should not exceed 1 mg; dosage may be increased to 2 mg if clinically indicated.1

Inducers of CYP3A4: potential pharmacokinetic interaction (decreased plasma eszopiclone concentrations).1

Protein-bound Drugs

Pharmacokinetic interaction unlikely; not highly bound to plasma proteins.1

Specific Drugs




Antifungals, azoles (itraconazole, ketoconazole)

Increased plasma eszopiclone concentrations; 2.2-fold increase in eszopiclone exposure reported following concomitant use of eszopiclone 3 mg and ketoconazole 400 mg1

Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1

CNS depressants (e.g., psychotropic drugs, anticonvulsants, antihistamines, alcohol)

Possible additive CNS-depressant effects1

Do not use with alcohol; consider dosage reduction if eszopiclone is used concomitantly with other CNS depressants1


Pharmacokinetic or pharmacodynamic interactions unlikely1

HIV protease inhibitors (nelfinavir, ritonavir)

Increased plasma eszopiclone concentrations1

Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1


No clinically important pharmacokinetic or pharmacodynamic interactions observed following single-dose administration of eszopiclone 3 mg with lorazepam 2 mg1 13

Macrolide antibiotics (clarithromycin, troleandomycin)

Increased plasma eszopiclone concentrations1

Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1


Increased plasma eszopiclone concentrations1

Initial eszopiclone dosage should not exceed 1 mg; may increase dosage to 2 mg if clinically indicated1


Decreased psychomotor performance noted following single-dose administration of eszopiclone 3 mg with olanzapine 10 mg;1 pharmacokinetic interaction unlikely1


Pharmacokinetic or pharmacodynamic interactions unlikely; concomitant use (eszopiclone 3 mg and paroxetine 20 mg daily for 7 days) did not alter relevant parameters1


Decreased plasma eszopiclone concentrations1


Pharmacokinetic or pharmacodynamic (PT) interactions unlikely1 13

Eszopiclone Pharmacokinetics



Rapidly absorbed following oral administration, with peak plasma concentration attained in about 1 hour.1 2 3 4


High-fat meal decreases peak plasma concentration by 21% and prolongs the time to peak plasma concentration by about 1 hour;1 effect on sleep onset may be decreased.1

Special Populations

In geriatric patients, AUC is increased by 41% compared with younger adults.1

In patients with severe hepatic impairment, systemic exposure is 2 times higher than in healthy individuals.1


Plasma Protein Binding

Approximately 52–59%.1



Extensively metabolized via oxidation and demethylation, principally by CYP3A4 and CYP2E1 to 2 major metabolites; (S)-N-desmethyl zopiclone is considerably less active than the parent drug, and (S)-zopiclone-N-oxide is inactive.1 2

Elimination Route

Racemic zopiclone excreted principally in urine (75%), mainly as metabolites.1 Similar excretion profile expected for eszopiclone, the S-isomer of racemic zopiclone;1 <10% of eszopiclone dose excreted unchanged in urine.1


Approximately 6 hours.1

Special Populations

In geriatric patients, half-life is approximately 9 hours.1





25°C (may be exposed to 15–30°C).1


  • Interacts with the CNS GABAA-receptor complex at binding domains located close to or allosterically coupled to benzodiazepine receptors.1 2 10 11

  • Pharmacologically similar to zaleplon and zolpidem.1 2 10 11

  • Structurally unrelated to benzodiazepines and other sedative and hypnotic agents that are commercially available in the US, including barbiturates, imidazopyridines (e.g., zolpidem), and pyrazolopyrimidines (e.g., zaleplon).1 2 3 5 10

  • S-enantiomer of zopiclone (a hypnotic agent not commercially available in the US).1

  • Binding affinity (in vitro) for benzodiazepine receptors is about 50 times that of the R-enantiomer of racemic zopiclone.2 10

Advice to Patients

  • Provide patient with a copy of manufacturer’s patient information.1

  • Importance of administering immediately before retiring or after attempting to fall asleep.1

  • Importance of taking only when able to get a full night’s sleep (i.e., ≥8 hours) before being active again.1

  • Importance of taking only as prescribed (e.g., not with or immediately after a high-fat meal); do not increase dosage or duration of therapy unless otherwise instructed by a clinician.1

  • Potential for drug to cause somnolence, dizziness, and/or coordination difficulties; importance of exercising caution when operating machinery or performing hazardous tasks.1

  • Advise of the possibility of adverse effects such as unpleasant taste, headache, and cold-like symptoms.1

  • Importance of reporting to clinicians any unusual and/or disturbing thoughts or behavior, memory impairment, or dependence/withdrawal symptoms after multiple dosing.1

  • Advise of possible rebound insomnia for 1 or 2 nights after discontinuance.1

  • Importance of avoiding alcohol-containing beverages or products.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as concomitant or past illnesses (e.g., depression, substance abuse).1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.1



Dosage Forms


Brand Names



Tablets, film-coated

1 mg

Lunesta (C-IV)


2 mg

Lunesta (C-IV)


3 mg

Lunesta (C-IV)


Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lunesta 1MG Tablets (SUNOVION PHARMACEUTICALS): 30/$228.99 or 90/$653.98

Lunesta 2MG Tablets (SUNOVION PHARMACEUTICALS): 30/$226.00 or 90/$661.96

Lunesta 3MG Tablets (SUNOVION PHARMACEUTICALS): 30/$230.99 or 90/$662.95

AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


1. Sepracor Inc. Lunesta (eszopiclone) tablets prescribing information. Marlborough, MA; 2005 Feb.

2. Mack A, Salazar JO. Eszopiclone: a novel cyclopyrrolone with potential benefit in both transient and chronic insomnia. Formulary. 2003; 38:582-93.

3. Krystal AD, Walsh JK, Laska E et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003; 26:793-9. [IDIS 527792] [PubMed 14655910]

4. Fernandez C, Martin C, Gimenez F et al. Clinical pharmacokinetics of zopiclone. Clin Pharmacokinet. 1995; 29:431-41. [PubMed 8787948]

5. Rosenberg R, Caron J, Roth T et al. An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults. Sleep Med. 2005; 6:15-22. [IDIS 528997] [PubMed 15680290]

6. Schenck CH, Mahowald MW, Sack RL. Assessment and management of insomnia. JAMA. 2003; 289:2475-9. [IDIS 499774] [PubMed 12759306]

7. Jacobs GD, Pace-Schott EF, Stickgold R et al. Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med. 2004; 164:1888-96. [IDIS 524535] [PubMed 15451764]

8. Morin CM, Colecchi C, Stone J et al. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999; 281:991-9. [IDIS 421436] [PubMed 10086433]

9. Walsh JK. Pharmacologic management of insomnia. J Clin Psychiatry. 2004; 65(suppl 16):41-5. [IDIS 526373] [PubMed 15575804]

10. Georgiev V. (S)-Zopiclone Sepracor. Curr Opin Investig Drugs. 2001; 2:271-3. [PubMed 11816843]

11. Anon. Eszopiclone (Lunesta), a new hypnotic. Med Lett Drugs Ther. 2005; 47:17-9. [PubMed 15767972]

12. Zammit GK, McNabb LJ, Caron J et al. Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin. 2004; 20:1979-91. [IDIS 528996] [PubMed 15701215]

13. Sepracor, Marlborough, MA: Personal communication.

14. Food and Drug Administration. Lunesta (eszopiclone) tablets. [March 14, 2007: Sepracor] MedWatch drug labeling changes. Rockville, MD; April 2007. From FDA websites and