Section 10 · Monograph

Eszopiclone

Reviewed Nov 2026FDA label

LunestaNonbenzodiazepine hypnotic (Z-drug)

Black Box Warning

COMPLEX SLEEP BEHAVIORS: Complex sleep behaviors, including sleepwalking, sleep-driving, and engaging in other activities while not fully awake, may occur following use of Lunesta. Some of these events have resulted in serious injuries, including death.
These behaviors appear to be more likely when Lunesta is taken with alcohol or other CNS depressants, and at doses exceeding the maximum recommended dose, but can occur with recommended doses and after a single dose.
Discontinue immediately if a patient experiences an episode of complex sleep behavior.
Lunesta is contraindicated in patients who have experienced a complex sleep behavior after taking eszopiclone.

Treatment of insomnia in adults, to improve sleep onset and/or sleep maintenance (studied in controlled trials up to 6 months).FDA-labeled

Adjunctive treatment for insomnia associated with generalized anxiety disorder (studied in combination with escitalopram).Off-label
Insomnia associated with major depressive disorder as adjunct to antidepressant therapy.Off-label
Perimenopausal/menopausal-associated insomnia.Off-label

Eszopiclone is a nonbenzodiazepine hypnotic of the cyclopyrrolone (pyrrolopyrazine) chemical class; it is the active S-enantiomer of racemic zopiclone.
Exact mechanism is unknown, but its hypnotic effect is believed to result from interaction with GABA-A receptor complexes at (or near) benzodiazepine binding sites, potentiating GABAergic inhibitory neurotransmission.
Structurally unrelated to benzodiazepines, zolpidem, or zaleplon, but pharmacologically shares sedative properties with the benzodiazepine class.

Adults: initiate at 1 mg orally immediately before bedtime, with at least 7-8 hours remaining before planned awakening; may titrate to 2 mg or 3 mg based on clinical response and tolerability. Maximum recommended dose is 3 mg once daily.
This 1 mg universal starting dose reflects an FDA-mandated May 2014 label revision that lowered the prior starting dose (previously 2 mg for most adults) for both men and women, based on next-morning driving-simulator and psychomotor/memory testing showing that the 3 mg dose produced impairment persisting up to 11.5 hours post-dose — even in patients who felt fully awake.
Elderly or debilitated patients: start at 1 mg; maximum 2 mg once daily.
Concomitant use with moderate or potent CYP3A4 inhibitors (e.g., ketoconazole): maximum 2 mg once daily.
Avoid dosing with or immediately after a high-fat/heavy meal.
Avoid abrupt discontinuation after extended nightly use due to risk of withdrawal/rebound insomnia; taper if used long-term.

History of complex sleep behaviors (e.g., sleepwalking, sleep-driving) after taking eszopiclone.
Known hypersensitivity to eszopiclone.

CNS depressants (opioids, benzodiazepines, alcohol, tricyclic antidepressants, antipsychotics): additive CNS and psychomotor depression; additive respiratory depression risk with opioids.
Ethanol: additive impairment of psychomotor performance; avoid concurrent use.
Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, nefazodone): ketoconazole increased eszopiclone exposure ~2.2-fold; reduce eszopiclone dose to a maximum of 2 mg.
CYP3A4 inducers (rifampin): decreased eszopiclone AUC by ~80%, which may reduce hypnotic efficacy.
No clinically significant pharmacokinetic interaction identified with digoxin or warfarin.
Other sedating agents (olanzapine): additive decrease in psychomotor performance reported.

Unpleasant/bitter taste (dysgeusia) — the most common adverse reaction and shows the clearest dose-response relationship.
Headache, somnolence, dizziness, dry mouth, nasopharyngitis/upper respiratory infection, anxiety, rash, hallucinations, viral infection.
Next-day psychomotor and memory impairment, which can occur even in the absence of subjective sleepiness.
Complex sleep behaviors — boxed warning.
Abnormal thinking/behavioral changes: decreased inhibition, aggression, agitation, hallucinations, depersonalization.
Worsening depression and emergence/worsening of suicidal ideation.
Rare anaphylaxis/angioedema (tongue, glottis, larynx).
Withdrawal/rebound insomnia with abrupt discontinuation after prolonged use.
Physical and psychological dependence potential (Schedule IV).

Screen for personal/family history of substance use disorder before prescribing.
Reassess if insomnia fails to improve within 7-10 days of treatment.
Monitor for emergence of complex sleep behaviors, especially early in treatment or after dose increases.
Monitor mood and for emergence/worsening of depression or suicidal ideation.
Assess for residual next-day sedation/psychomotor impairment, particularly at the 3 mg dose.
Monitor hepatic function and adjust dosing in hepatic impairment.
Periodically reassess ongoing need for therapy; prescribe minimum quantity feasible in patients at risk for intentional overdose.
Monitor for tolerance, dose escalation, or withdrawal symptoms with long-term use.

Pregnancy: Available human data are insufficient to establish a drug-associated risk of major birth defects or miscarriage. Neonates exposed late in pregnancy are at risk for sedation and/or respiratory depression. Animal studies did not show teratogenicity but showed decreased offspring body weight and survival at high maternal exposures.
Lactation: No data on presence in human milk, effects on the breastfed infant, or on milk production; monitor infants for sedation if used during breastfeeding.
Use in pregnancy is not recommended; weigh risks/benefits and consider non-pharmacologic therapy first-line.