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. |
| Molecular Weight | 388.81 |
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 | Limited human data; animal studies show increased risk of fetal malformations at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient data; avoid use due to potential risks. |
| 3rd trimester | Use near term may cause neonatal respiratory depression and withdrawal symptoms. Avoid use in late pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for LUNESTA (LUNESTA).
| Placental transfer | Eszopiclone crosses the placenta, as evidenced by measurable concentrations in cord blood. The degree of transfer is moderate. |
| Breastfeeding | Eszopiclone is excreted into human breast milk in small amounts. Caution is advised due to potential sedative effects on the infant. Monitor infant for drowsiness and feeding difficulties. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to eszopicloneHistory of substance abuseSevere hepatic impairmentMyasthenia gravisNarrow-angle glaucoma
| 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 |
| Food/Dietary | High-fat meals delay absorption and reduce peak concentration. Avoid grapefruit juice (may increase exposure). Alcohol increases CNS depression and may impair motor function; avoid concurrent use. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| 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 | 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. |
| Clinical Pearls | LUNESTA (eszopiclone) is a nonbenzodiazepine hypnotic used for insomnia. Onset is rapid; instruct patients to take immediately before bed with at least 7-8 hours of sleep remaining. Avoid coadministration with other CNS depressants. Dose adjustment needed in hepatic impairment (max 2 mg). Use lowest effective dose, particularly in elderly (start 1 mg) due to fall risk. Do not exceed 3 mg/day. Discontinue gradually after prolonged use to avoid rebound insomnia. |
| Patient Advice | Take LUNESTA only when you have at least 7-8 hours to sleep. · Do not take with or after a high-fat meal as it may delay onset. · Avoid alcohol and other sedatives while taking this medication. · Do not drive or operate machinery until you know how LUNESTA affects you. · May cause daytime drowsiness, memory problems, or unusual behaviors (e.g., sleep-driving). Stop and contact your doctor if these occur. · Do not take more than prescribed; risk of dependence increases with higher doses and longer use. · Inform your doctor if you have liver disease, depression, or a history of substance abuse. |