LUNESTA™ (eszopiclone) TABLETS
1 mg, 2 mg, 3 mg
PRESCRIBING INFORMATION
DESCRIPTION:
LUNESTA (eszopiclone) is a nonbenzodiazepine hypnotic agent that is a pyrrolopyrazine
derivative of the cyclopyrrolone class. The chemical name of eszopiclone is (+)-(5S)-6-
(chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b] pyrazin-5-yl 4-methyl- piperazine-1-
carboxylate. Its molecular weight is 388.81, and its empirical formula is C17H17ClN6O3.
Eszopiclone has a single chiral center with an (S)-configuration. It has the following chemical
structure:
N
N
N
N
O
C N N CH3
Cl
O
O
H
Eszopiclone is a white to light-yellow crystalline solid. Eszopiclone is very slightly soluble in
water, slightly soluble in ethanol, and soluble in phosphate buffer (pH 3.2).
Eszopiclone is formulated as film-coated tablets for oral administration. LUNESTA tablets
contain 1 mg, 2 mg, or 3 mg eszopiclone and the following inactive ingredients: calcium
phosphate, colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose, magnesium
stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide, and triacetin. In
addition, both the 1 mg and 3 mg tablets contain FD&C Blue #2.
 
Pharmacodynamics
The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is
believed to result from its interaction with GABA-receptor complexes at binding domains
located close to or allosterically coupled to benzodiazepine receptors. Eszopiclone is a
nonbenzodiazepine hypnotic that is a pyrrolopyrazine derivative of the cyclopyrrolone class with
a chemical structure unrelated to pyrazolopyrimidines, imidazopyridines, benzodiazepines,
barbiturates, or other drugs with known hypnotic properties.
Pharmacokinetics
The pharmacokinetics of eszopiclone have been investigated in healthy subjects (adult and
elderly) and in patients with hepatic disease or renal disease. In healthy subjects, the
pharmacokinetic profile was examined after single doses of up to 7.5 mg and after once-daily
administration of 1, 3, and 6 mg for 7 days. Eszopiclone is rapidly absorbed, with a time to peak
concentration (tmax) of approximately 1 hour and a terminal-phase elimination half-life (t1/2) of
approximately 6 hours. In healthy adults, LUNESTA does not accumulate with once-daily
administration, and its exposure is dose-proportional over the range of 1 to 6 mg.
Absorption And Distribution
Eszopiclone is rapidly absorbed following oral administration. Peak plasma concentrations are
achieved within approximately 1 hour after oral administration. Eszopiclone is weakly bound to
plasma protein (52-59%). The large free fraction suggests that eszopiclone disposition should
not be affected by drug-drug interactions caused by protein binding. The blood-to-plasma ratio
for eszopiclone is less than one, indicating no selective uptake by red blood cells.
Metabolism
Following oral administration, eszopiclone is extensively metabolized by oxidation and
demethylation. The primary plasma metabolites are (S)-zopiclone-N-oxide and (S)-N-desmethyl
zopiclone; the latter compound binds to GABA receptors with substantially lower potency than
eszopiclone, and the former compound shows no significant binding to this receptor. In vitro
studies have shown that CYP3A4 and CYP2E1 enzymes are involved in the metabolism of
eszopiclone. Eszopiclone did not show any inhibitory potential on CYP450 1A2, 2A6, 2C9,
2C19, 2D6, 2E1, and 3A4 in cryopreserved human hepatocytesPharmacokinetics
The pharmacokinetics of eszopiclone have been investigated in healthy subjects (adult and
elderly) and in patients with hepatic disease or renal disease. In healthy subjects, the
pharmacokinetic profile was examined after single doses of up to 7.5 mg and after once-daily
administration of 1, 3, and 6 mg for 7 days. Eszopiclone is rapidly absorbed, with a time to peak
concentration (tmax) of approximately 1 hour and a terminal-phase elimination half-life (t1/2) of
approximately 6 hours. In healthy adults, LUNESTA does not accumulate with once-daily
administration, and its exposure is dose-proportional over the range of 1 to 6 mg.
Absorption And Distribution
Eszopiclone is rapidly absorbed following oral administration. Peak plasma concentrations are
achieved within approximately 1 hour after oral administration. Eszopiclone is weakly bound to
plasma protein (52-59%). The large free fraction suggests that eszopiclone disposition should
not be affected by drug-drug interactions caused by protein binding. The blood-to-plasma ratio
for eszopiclone is less than one, indicating no selective uptake by red blood cells.
Metabolism
Following oral administration, eszopiclone is extensively metabolized by oxidation and
demethylation. The primary plasma metabolites are (S)-zopiclone-N-oxide and (S)-N-desmethyl
zopiclone; the latter compound binds to GABA receptors with substantially lower potency than
eszopiclone, and the former compound shows no significant binding to this receptor. In vitro
studies have shown that CYP3A4 and CYP2E1 enzymes are involved in the metabolism of
eszopiclone. Eszopiclone did not show any inhibitory potential on CYP450 1A2, 2A6, 2C9,
2C19, 2D6, 2E1, and 3A4 in cryopreserved human hepatocytes.