Generic Name

Lunesta

Mechanism

Lunesta (generic name *eszopiclone*) is a non‑benzodiazepine hypnotic that selectively augments GABA‑A receptor activity.
• Binds to the benzodiazepine site on the β3 subunit of GABA‑A receptors, especially the α1 subunit, enhancing chloride influx.
• Produces rapid onset (5–15 min) and facilitates sleep initiation and maintenance with minimal disinhibition of other CNS functions.

Pharmacokinetics

• Absorption: Rapid, peak plasma concentration in 0.5–1 h.
• Metabolism: Primarily hepatic via CYP3A4/5; metabolite *N‑deethyl‑eszopiclone* is inactive.
• Elimination half‑life: 6–6.5 h (short‑acting hypnotic).
• Excretion: 44 % renal, 56 % biliary; no active metabolites accumulate with standard dosing.

Indications

• Short‑term treatment of primary insomnia (sleep onset or maintenance).
• Approved for up to 4 weeks in adults; extended use may be considered with careful monitoring.

Contraindications

• Absolute contraindications:
• Severe hepatic impairment (Child‑Pugh B/C).
• Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir).
• Cautions:
• Elderly patients—higher risk of sedation, impaired cognition, and falls.
• History of substance abuse—possible dependence.
• Severe respiratory conditions (COPD, asthma) may worsen sleep‑disordered breathing.

Dosing

• Take bedtime, with a full glass of water.
• Use a sleep diary to gauge efficacy and adjust dose.

Adverse Effects

• Common (≥10 %):
• Somnolence, dizziness, dry mouth, dysgeusia (taste alteration).
• Mild gastrointestinal upset.
• Serious (≤1 %):
• Drug‑induced sleep‑walking, complex behavior (e.g., eating, driving).
• Amnesia of episodes.
• Respiratory depression in overdose or with CNS depressant co‑therapy.
• Rare (≤0.1 %):
• Hallucinations, suicidal ideation, paradoxical agitation.

Monitoring

• Baseline: Liver function tests, renal profile, CBC if at risk of bone marrow suppression.
• During therapy:
• Cognitive/neurologic assessment (especially in elderly).
• Falls risk evaluation.
• Sleep logs and adverse event interviews at each visit.
• Laboratory: Consider periodic monitoring in patients with hepatic or renal impairment.

Clinical Pearls

• Start Low, Go Slow: Initiate at the lowest dose; many patients achieve satisfactory sleep with 1 mg in the elderly.
• Avoid Alcohol: Alcohol potentiates GABAergic sedative effect, increasing fall and overdose risk.
• CYP3A4 Interactors: Patients on macrolide antibiotics or antifungals may need dose reduction – consider a 1‑week washout if necessary.
• Morning Residual Sedation: Some patients use an “over‑the‑counter” mid‑dose strategy; avoid one‑hour intervals—this can lead to accumulation and next‑day sedation.
• Sleep Architecture: Unlike benzodiazepines, *eszopiclone* minimally reduces REM sleep, making it preferable for patients with REM‑behavior disorders.

> *Note: Always tailor therapy to the individual's comorbidities and concurrent meds to mitigate risk of dependence or respiratory depression.*