SLEEPGABA 3

Indications

• Insomnia
• Sleep maintenance difficulties
• Sleep onset difficulties

Dosage

Children: Eszopiclone is not recommended for use in children and adolescents under 18 years of age. Please refer to appropriate guidelines for alternative treatments.

Adults: The recommended starting dose is 2 mg taken immediately before bedtime. If necessary, the dose may be increased to a maximum of 3 mg. Dosing should be individualized based on patient response and tolerability.

Mechanism of action

The exact mechanism of action of eszopiclone is unknown, but it is believed to involve binding to GABA receptor complexes at sites near benzodiazepine receptors. It has a particular affinity for GABA-A receptor subunits 1, 3, and 5, which increases GABA-A channel currents, leading to central nervous system depression.

Pharmacodynamics

Eszopiclone induces sleep rapidly and decreases sleep latency while aiding in maintaining sleep, thus preventing frequent awakenings. It exhibits central nervous system depressant effects, which can impair alertness and motor coordination, particularly the following morning. Patients are advised against engaging in activities requiring full mental alertness and to avoid alcohol or other CNS depressants while using eszopiclone.

Pharmacokinetics

Eszopiclone is rapidly absorbed following oral administration, with peak plasma concentrations typically occurring within 1 hour. It has a half-life of approximately 6 hours, allowing for effective sleep maintenance. The drug is metabolized primarily in the liver via cytochrome P450 enzymes, with renal excretion of metabolites as the main route of elimination.

Contra-indications

• Hypersensitivity to eszopiclone or any component of the formulation
• Severe respiratory insufficiency
• Sleep apnea syndrome

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Headache
• Nausea
• Complex sleep behaviors (e.g., sleep-driving)
• Next-day sedation
• Anaphylaxis

Interactions

• CNS depressants (e.g., alcohol, benzodiazepines) may enhance sedative effect
• Strong CYP3A4 inhibitors (e.g., ketoconazole) may increase eszopiclone levels
• Strong inducers of CYP3A4 (e.g., rifampicin) may decrease eszopiclone levels

Precautions

• Use with caution in elderly patients due to increased sensitivity
• Risk of dependence and abuse, though lower than with other hypnotics
• Patients should be monitored for signs of complex sleep behaviors
• Caution advised while driving or performing tasks requiring mental alertness

Pregnancy

Eszopiclone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available.

Breast-feeding

It is not known whether eszopiclone is excreted in human milk. Caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets: 1 mg, 2 mg, 3 mg

Mechanism of action

The exact mechanism of action of eszopiclone is unknown at this time but is thought to occur via binding with the GABA receptor complexes at binding sites located near benzodiazepine receptors, possibly explaining its hypnotic and sedative effects. It has particular affinity for GABA-A (or GABAA) receptor subunits 1, 3 and 5. Eszopiclone increases GABA-A channel currents significantly. GABA-A channels are major inhibitory channels that cause CNS depression when their receptors are activated. Eszopiclone, the S-enantiomer of zopiclone (not commercially available in the US), is a sedative and hypnotic agent that is structurally unrelated to benzadiazepines and other sedative and hypnotic agents that are commercially available in the US, including barbiturates, imidazopyridines (e.g., zolpidem), and pyrazolopyrimidines (e.g., zaleplon). Eszopiclone is pharmacologically similar to zaleplon and zolpidem; all of these agents have been shown to interact with the CNS gamma-aminobutyric acid (GABA) receptor complex at binding domains located close to or allosterically coupled to benzodiazepine receptors. The precise mechanism of action of eszopiclone as a hypnotic is unknown. Its pharmalogic effect is believed to result from its interaction with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors.

Pharmacodynamics

Eszopiclone rapidly induces sleep and decreases sleep latency. It also aids in the maintenance of sleep, preventing frequent awakenings. This drug has shown anticonvulsant and muscle relaxant properties in animals but is used in humans for its sedating effects. Eszopiclone is a central nervous system depressant with various effects. These include changes in alertness and motor coordination and the risk of next morning impairment, increasing with the amount of eszopiclone administered. Exercise caution and advise against driving a motor vehicle or activities that require full mental alertness the next morning. Complex sleep behaviors may result from eszopiclone use. Eszopiclone should be discontinued in these cases. Avoid the use of alcohol and other CNS depressants when eszopiclone is administered. Advise patients to skip the eszopiclone dose if alcohol has been consumed before bed or during the evening. Use the smallest dose of eszopiclone as possible, especially in elderly patients, who may experience exaggerated drug effects. Though the potential for dependence and abuse with eszopiclone is lower than for other hypnotic drugs, this drug has been abused and is known to cause dependence.