LUNESTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LUNESTA (LUNESTA).
Nonbenzodiazepine hypnotic that binds to GABA-A receptors at the benzodiazepine binding site, enhancing GABAergic inhibitory neurotransmission.
| Metabolism | Primarily via CYP3A4; also CYP2E1 involvement; active metabolite (desmethylzopiclone) has some activity. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2E1; renal excretion of metabolites accounts for approximately 80% of total clearance, with about 2-4% excreted unchanged in urine. Fecal excretion contributes less than 10%. |
| Half-life | Terminal elimination half-life is approximately 6 hours in young adults and about 9 hours in elderly patients. This supports once-nightly dosing for insomnia. |
| Protein binding | 52% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 4.0 L/kg, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 80%. |
| Onset of Action | Oral: Onset of sleep induction occurs within 30 minutes to 1 hour after oral administration. |
| Duration of Action | Duration of hypnotic effect is approximately 6-8 hours, supporting sleep maintenance with minimal next-day residual effects due to its intermediate half-life. |
1 mg, 2 mg, or 3 mg orally once immediately before bedtime; not to exceed 3 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment. |
| Liver impairment | Child-Pugh Class A or B: 1 mg initially, not to exceed 2 mg; Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for patients under 18 years; safety and efficacy not established. |
| Geriatric use | Initial dose 1 mg orally once at bedtime; total daily dose not to exceed 2 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LUNESTA (LUNESTA).
| Breastfeeding | Eszopiclone is excreted into breast milk (M/P ratio approximately 0.5, estimated infant dose 1.4% of maternal weight-adjusted dose). Avoid breastfeeding due to potential sedation and respiratory effects in the infant. |
| Teratogenic Risk | Limited human data; animal studies show increased fetal loss and delayed ossification at high doses. First trimester: risk unknown, avoid unless essential. Second and third trimesters: risk of neonatal withdrawal, respiratory depression, and hypotonia if used near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Previous allergic reaction to eszopiclone or zopiclone"]
| Precautions | ["Complex sleep behaviors (e.g., sleep-driving, sleep-eating; discontinue if occurs)","CNS depressant effects (additive with alcohol and other sedatives)","Anaphylaxis and angioedema","Depression and suicide risk","Next-day impairment (especially with higher doses or long-acting formulations)","Elderly/debilitated patients: increased risk of falls","Abuse and dependence potential","Tolerance and withdrawal symptoms"] |
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| Monitor for fetal growth, amniotic fluid index, and fetal heart rate patterns during chronic use. Near term, assess neonatal respiratory status, muscle tone, and withdrawal symptoms (irritability, tremors). |
| Fertility Effects | No known significant impairment of fertility in animal studies. In humans, no data suggesting detrimental effects on fertility. |