Eszopiclone

Approved Indications:

• Insomnia:
  Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Clinically Accepted Off-Label Uses:

• Short-term management of other sleep disorders as determined by the physician.
• Occasionally used in patients with psychiatric disorders to improve sleep quality.

Route: Oral

Adults:

• Initial Dose: 1 mg immediately before bedtime.
• Maintenance Dose: May be increased to 2 mg or 3 mg depending on efficacy and tolerability.
• Maximum Dose: 3 mg daily.

Elderly or Debilitated Patients:

• Start at 1 mg once daily at bedtime. Dose titration should be cautious.

Pediatrics:

• Safety and efficacy not established; not recommended.

Hepatic Impairment:

• Use with caution; no specific dose adjustment recommended but close monitoring advised.

Renal Impairment:

• No specific adjustment needed; monitor for increased sedation.

Administration Instructions:

• Take immediately before bedtime.
• Ensure at least 7–8 hours available for sleep.
• Avoid taking after a heavy meal (which can delay onset).

Eszopiclone is a non-benzodiazepine hypnotic of the cyclopyrrolone class that selectively binds to the benzodiazepine site on the GABA_A receptor complex. By enhancing GABAergic inhibitory neurotransmission, it increases the frequency of chloride channel opening, resulting in neuronal hyperpolarization and CNS depression. This action facilitates the initiation and maintenance of sleep by promoting sedation and reducing sleep latency without significant muscle relaxation or anticonvulsant effects.

• Absorption: Rapid oral absorption; peak plasma concentration reached in approximately 1 hour.
• Bioavailability: Approximately 75–80%.
• Distribution: Widely distributed; crosses the blood-brain barrier.
• Metabolism: Primarily hepatic via CYP3A4 and CYP2E1 pathways to inactive metabolites.
• Half-life: Approximately 6 hours (range 5–7 hours).
• Excretion: Mainly renal elimination of metabolites.

• Pregnancy:
  Classified as FDA Pregnancy Category C. Animal studies have shown adverse effects on the fetus, but no adequate human studies exist. Use only if clearly needed and benefits outweigh risks.
• Lactation:
  Excreted in breast milk in small amounts; caution advised. Breastfeeding is generally not recommended during treatment.

• Primary Class: Hypnotic/Sedative
• Subclass: Non-benzodiazepine sedative-hypnotic (Cyclopyrrolone class)

• Known hypersensitivity to eszopiclone or any formulation components.
• Patients with a history of complex sleep behaviors (e.g., sleepwalking) related to sedative use.
• Severe respiratory impairment or sleep apnea syndrome (due to CNS depressant effects).
• Myasthenia gravis (risk of worsening muscle weakness).
• Severe hepatic impairment (use with extreme caution).

• CNS Depression: Potential for next-day impairment; caution in activities requiring full alertness (e.g., driving).
• Complex Sleep Behaviors: Sleepwalking, sleep-driving, and other activities with no memory of the event. Discontinue if these occur.
• Dependence and Withdrawal: Risk of physical and psychological dependence; taper doses rather than abrupt discontinuation.
• Respiratory Depression: Use cautiously in patients with compromised respiratory function.
• Suicidal Ideation: Monitor patients for worsening depression or emergent suicidal thoughts.
• Elderly: Increased sensitivity; risk of falls and cognitive impairment.
• Use Duration: Recommended for short-term use (typically 2–4 weeks); extended use only under medical supervision.

Common Side Effects:

• Dysgeusia (bitter or metallic taste)
• Headache
• Somnolence
• Dry mouth
• Dizziness
• Fatigue

Serious/Rare Side Effects:

• Complex sleep behaviors (sleepwalking, sleep-driving)
• Allergic reactions including anaphylaxis and angioedema
• Cognitive and memory impairment
• Depression worsening or suicidal ideation
• Respiratory depression in susceptible individuals

Timing:

• Side effects typically appear early in treatment and may diminish with continued use.

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase eszopiclone plasma levels, increasing sedation risk.
• CYP3A4 inducers (e.g., rifampin, carbamazepine): May reduce efficacy by increasing metabolism.
• CNS Depressants (e.g., alcohol, opioids, benzodiazepines): Additive sedative and respiratory depressant effects; avoid concurrent use or use cautiously.
• Other hypnotics or sedatives: Increased risk of sedation and cognitive impairment.

• Updated clinical guidelines emphasize caution with hypnotics in elderly patients due to fall risk and cognitive effects.
• FDA safety communications highlight risks of complex sleep behaviors; boxed warnings reinforced.
• Newer guidelines recommend the lowest effective dose and shortest duration to mitigate dependence and adverse events.

• Store at 20°C to 25°C (68°F to 77°F), with permitted excursions between 15°C and 30°C (59°F to 86°F).
• Protect from moisture and light.
• Keep in original container tightly closed.
• Keep out of reach of children.
• No special reconstitution or refrigeration required.