Introduction
Lunesta (eszopiclone) is a non-benzodiazepine hypnotic agent approved by the FDA for the treatment of insomnia. It belongs to the cyclopyrrolone class of medications and is classified as a Schedule IV controlled substance due to its potential for abuse and dependence.
Mechanism of Action
Eszopiclone exerts its therapeutic effects through positive allosteric modulation of the gamma-aminobutyric acid (GABA-A) receptor complex. By enhancing GABAergic inhibition in the central nervous system, it promotes sedation, reduces sleep latency, and improves sleep maintenance.
Indications
- Treatment of insomnia characterized by difficulty with sleep initiation and/or sleep maintenance
- Short-term management of insomnia (typically 7-10 days, with longer use requiring reevaluation)
Dosage and Administration
Adults:- Initial dose: 1 mg immediately before bedtime
- May increase to 2-3 mg if clinically indicated
- Maximum recommended dose: 3 mg
- Severe hepatic impairment: Initial dose should not exceed 1 mg
- Elderly/debilitated patients: Initial dose of 1 mg recommended
- Concomitant use with CYP3A4 inhibitors: Consider dose reduction
- Take immediately before bedtime
- Ensure at least 7-8 hours dedicated to sleep
- Do not take with or immediately after a high-fat meal
Pharmacokinetics
Absorption: Rapidly absorbed with peak concentrations occurring approximately 1 hour post-administration. High-fat meals may delay absorption. Distribution: Volume of distribution approximately 59 L. Protein binding is 52-59%. Metabolism: Extensively metabolized primarily by CYP3A4 and to a lesser extent by CYP2E1. Major metabolites include (S)-N-desmethyl zopiclone and eszopiclone N-oxide. Elimination: Half-life of approximately 6 hours. Excreted primarily in urine (75%) as metabolites, with feces accounting for the remainder.Contraindications
- Hypersensitivity to eszopiclone or any component of the formulation
- History of complex sleep behaviors while taking eszopiclone
Warnings and Precautions
Boxed Warning:- Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake
- CNS depressant effects: Risk of impaired alertness and coordination
- Next-day impairment: May occur even if patient feels fully awake
- Tolerance and dependence: Risk of abuse, dependence, and withdrawal symptoms
- Worsening depression/suicidal ideation: Monitor patients with depression carefully
- Respiratory depression: Use with caution in patients with compromised respiratory function
- Anaphylaxis and angioedema: Has been reported
Drug Interactions
Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): Increase eszopiclone exposure - reduce dose to 1 mg CNS depressants (e.g., alcohol, opioids, benzodiazepines): Additive CNS depression CYP3A4 inducers (e.g., rifampin, carbamazepine): May decrease eszopiclone efficacyAdverse Effects
Common (≥2%):- Unpleasant taste (dysgeusia)
- Headache
- Somnolence
- Dizziness
- Dry mouth
- Nervousness
- Complex sleep behaviors
- Anaphylaxis
- Angioedema
- Memory impairment
- Depression/suicidal ideation
- Respiratory depression
Monitoring Parameters
- Sleep patterns and quality
- Daytime alertness and cognitive function
- Signs of tolerance or dependence
- Mood changes, especially in patients with depression
- Adverse effects, particularly CNS depression
- Renal and hepatic function in patients with impairment
Patient Education
- Take immediately before bedtime with at least 7-8 hours available for sleep
- Do not consume alcohol while taking Lunesta
- Report any episodes of sleep-walking, sleep-driving, or other unusual behaviors
- Be aware of possible next-day impairment when driving or operating machinery
- Do not increase dose without consulting healthcare provider
- Inform healthcare provider of all medications being taken
- Report any signs of allergic reaction or mood changes
- Avoid abrupt discontinuation after prolonged use
References
1. FDA Prescribing Information: Lunesta (eszopiclone) tablets 2. Krystal AD, et al. Sleep Med. 2003;4(1):13-18 3. Zammit GK, et al. J Clin Sleep Med. 2009;5(6):571-581 4. Roth T, et al. Sleep Med. 2005;6(5):427-434 5. American Academy of Sleep Medicine. J Clin Sleep Med. 2017;13(2):307-349 6. Scharf MB, et al. J Clin Psychiatry. 2005;66(4):469-476 7. Drug Facts and Comparisons. Facts & Comparisons [database online]
Note: This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.