Usage
- Eszopiclone is prescribed for the short-term treatment of insomnia, characterized by difficulty falling asleep, staying asleep, or both.
- Pharmacological classification: Sedative-hypnotic; Non-benzodiazepine hypnotic of the pyrazolopyrimidine class.
- Mechanism of action: Eszopiclone enhances the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system. By binding to specific GABA-A receptor subtypes, it increases the inhibitory effects of GABA, leading to sedation and promoting sleep.
Alternate Names
- International and regional variations: There are no widely used international variations of the name “eszopiclone”.
- Brand names: Lunesta
How It Works
- Pharmacodynamics: Eszopiclone binds selectively to specific subtypes of the GABA-A receptor, increasing the inhibitory effects of GABA and leading to sedation and sleep.
- Pharmacokinetics:
- Absorption: Eszopiclone is rapidly absorbed after oral administration, reaching peak plasma concentrations in approximately 1 to 1.3 hours. Absorption may be slowed if taken with or immediately after a heavy, high-fat meal.
- Metabolism: Primarily metabolized in the liver, involving CYP3A4 enzymes, to inactive metabolites.
- Elimination: Excreted primarily in urine (less than 10% as unchanged drug) and feces. The elimination half-life is approximately 6 hours, implying that most of the drug will be cleared from the body within a day.
- Mode of action: Eszopiclone acts by binding selectively to GABA-A receptor subtypes, particularly those containing the alpha-1 subunit. This binding enhances the inhibitory effects of GABA, reducing neuronal excitability and promoting sleep.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Eszopiclone binds to GABA-A receptors and modulates GABA neurotransmission by increasing the frequency of chloride channel opening. It does not directly inhibit CYP enzymes but can be affected by drugs that inhibit or induce CYP3A4.
- Elimination pathways: Eszopiclone is primarily metabolized by hepatic CYP3A4 enzymes, with subsequent renal excretion of metabolites. A small amount is excreted unchanged in urine.
Dosage
Standard Dosage
Adults:
- Initial dose: 1 mg orally, immediately before bedtime.
- Dose increase: May be increased to 2 mg or 3 mg if clinically indicated, based on individual response and tolerability.
- Maximum dose: 3 mg once daily.
- Administration: Take immediately before bedtime, preferably on an empty stomach. Allow at least 7-8 hours of sleep time after taking the medication.
Children:
- Eszopiclone is not recommended for use in children under 18 years of age, as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Initial dose: 1 mg immediately before bedtime. Maximum dose: 2 mg once daily. Start low and go slow due to increased sensitivity and higher risk of next-day impairment.
- Patients with Renal Impairment: No dose adjustment is typically required, but caution is advised.
- Patients with Hepatic Dysfunction:
- Mild to moderate impairment: No dose adjustment is typically required.
- Severe impairment: Initial dose: 1 mg immediately before bedtime. Maximum dose: 2 mg once daily.
- Patients with Comorbid Conditions: Use with caution in patients with respiratory disorders (e.g., COPD, sleep apnea), psychiatric disorders, history of substance abuse, or depression. Adjust dosage or consider alternatives as needed.
Clinical Use Cases
Eszopiclone is primarily indicated for the short-term treatment of insomnia and is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations.
Dosage Adjustments
- Concomitant CYP3A4 Inhibitors: Reduce the eszopiclone dose, starting with 1 mg and not exceeding 2 mg if needed.
- Hepatic Impairment (severe): Maximum dose: 2 mg.
- Elderly or Debilitated Patients: Maximum dose: 2 mg.
- Concomitant CNS Depressants: Adjust dosage to avoid additive effects.
Side Effects
Common Side Effects
- Unpleasant taste (dysgeusia)
- Headache
- Dry mouth
- Drowsiness
- Dizziness
Rare but Serious Side Effects
- Severe allergic reactions (anaphylaxis, angioedema)
- Complex sleep behaviors (sleepwalking, sleep-driving, eating while asleep)
- Worsening of depression or suicidal thoughts
- Hallucinations
- Amnesia
Long-Term Effects
- Potential for dependence and withdrawal symptoms with prolonged use (rebound insomnia, anxiety, tremors).
- Cognitive impairment.
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Angioedema
- Complex sleep behaviors
- Severe CNS depression
Contraindications
- Known hypersensitivity to eszopiclone.
- History of complex sleep behaviors while taking eszopiclone or similar medications.
Drug Interactions
- CNS Depressants (alcohol, benzodiazepines, opioids): Additive CNS depression.
- CYP3A4 Inhibitors (ketoconazole, itraconazole, clarithromycin): Increased eszopiclone levels.
- CYP3A4 Inducers (rifampicin, carbamazepine, St. John’s Wort): Decreased eszopiclone levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (animal studies have shown adverse effects, but there are no adequate and well-controlled studies in pregnant women).
- Fetal risks: Potential for fetal harm, especially in the first trimester.
- Breastfeeding: Eszopiclone is excreted in breast milk. Use with caution or consider an alternative if breastfeeding.
Drug Profile Summary
- Mechanism of Action: Enhances GABAergic neurotransmission by binding to GABA-A receptors.
- Side Effects: Unpleasant taste, headache, dry mouth, drowsiness, dizziness, complex sleep behaviors, worsening of depression, suicidal thoughts.
- Contraindications: Hypersensitivity to eszopiclone, history of complex sleep behaviors with similar drugs.
- Drug Interactions: CNS depressants, CYP3A4 inhibitors and inducers.
- Pregnancy & Breastfeeding: Category C; use with caution. Excreted in breast milk.
- Dosage: Adults: 1-3 mg HS; Elderly: 1-2 mg HS.
- Monitoring Parameters: Observe for adverse effects, especially complex sleep behaviors, next-day impairment, and signs of dependence or withdrawal.
Popular Combinations
Eszopiclone is generally not used in combination with other hypnotics. Concomitant use with other CNS depressants should be carefully monitored.
Precautions
- General Precautions: Evaluate for underlying sleep disorders, psychiatric conditions, and substance abuse. Monitor for adverse effects, particularly complex sleep behaviors and next-day impairment.
- Specific Populations: See “Dosage - Special Cases” section.
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. Do not drive or operate machinery until the effects of the medication have worn off.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Eszopiclone?
A: Adults: Initial dose is 1 mg orally immediately before bedtime. It can be increased to 2 mg or 3 mg if needed. Elderly patients: 1 mg initially, maximum 2 mg. Do not exceed 3 mg per day for adults or 2 mg per day for elderly patients.
Q2: How should Eszopiclone be taken?
A: Take it orally, immediately before bedtime, on an empty stomach. Allow for at least 7-8 hours of sleep time.
Q3: What are the common side effects of Eszopiclone?
A: Common side effects include unpleasant taste, headache, dry mouth, drowsiness, and dizziness.
Q4: Who should not take Eszopiclone?
A: Patients with known hypersensitivity to eszopiclone or a history of complex sleep behaviors with similar drugs.
Q5: What are the serious side effects of Eszopiclone?
A: Severe allergic reactions, complex sleep behaviors (sleepwalking, sleep-driving), worsening of depression, suicidal thoughts, and hallucinations.
Q6: Does Eszopiclone interact with other medications?
A: Yes, it can interact with CNS depressants (alcohol, benzodiazepines, opioids), CYP3A4 inhibitors, and CYP3A4 inducers.
Q7: Can Eszopiclone be used during pregnancy or breastfeeding?
A: Use with caution during pregnancy (Category C). Eszopiclone is excreted in breast milk; use with caution or consider an alternative.
Q8: Can I develop dependence on Eszopiclone?
A: Prolonged use can lead to dependence and withdrawal symptoms upon discontinuation. Use it for the shortest duration necessary.
Q9: What should I do if I experience complex sleep behaviors while taking Eszopiclone?
A: Discontinue the medication immediately and contact your doctor.
Q10: Does Eszopiclone affect driving ability?
A: Yes, eszopiclone can cause next-day drowsiness and impair cognitive function. Avoid driving or operating machinery after taking it.
