What are the recommended dosing, duration, contraindications, and safety precautions for Lunesta (eszopiclone) in adults, including elderly patients and those with hepatic impairment?

Lunesta (Eszopiclone) for Insomnia: Dosing, Duration, and Safety

Recommended Dosing

Start eszopiclone 2 mg at bedtime for adults aged 18–64 years, taken within 30 minutes of bedtime with at least 7 hours remaining before planned awakening. 1

Standard Adult Dosing (18–64 years)

• Initial dose: 2 mg at bedtime 1
• Maximum dose: 3 mg if 2 mg is well-tolerated but insufficient after 1–2 weeks 1
• Take on an empty stomach to maximize effectiveness 1

Elderly Patients (≥65 years)

• Initial dose: 1 mg at bedtime 1
• Maximum dose: 2 mg (do not exceed this dose in elderly patients) 1, 2
• Lower doses required due to increased sensitivity, prolonged half-life (~9 hours vs 6 hours), and elevated fall risk 3, 1

Hepatic Impairment

• Mild-to-moderate impairment: Start 1 mg, maximum 2 mg 1
• Severe impairment: Start 1 mg, maximum 2 mg (use with caution due to reduced clearance) 1

Renal Impairment

• No dose adjustment necessary 3

Duration of Treatment

FDA labeling indicates eszopiclone is intended for short-term use (≤4 weeks) for acute insomnia, though 6-month trials demonstrate sustained efficacy without tolerance. 2, 1

• Short-term evidence: Robust data support 4–12 weeks of use 1
• Long-term use: Studies up to 6–12 months show sustained benefit without tolerance development 4, 5, 3
• Critical caveat: The American College of Physicians states there is insufficient evidence to determine the balance of benefits and harms beyond 4 weeks 2
• Practical approach: Use the lowest effective dose for the shortest necessary duration, with periodic reassessment every 2–4 weeks 1, 2

Contraindications and Precautions

Absolute Contraindications

• History of complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating) on any hypnotic 1
• Severe hepatic impairment requires dose reduction, not absolute contraindication 1

Relative Contraindications and Cautions

• Pregnancy and nursing: Not recommended 1
• Age <18 years: Safety and effectiveness not established 1
• Depression with suicidal ideation: Monitor closely for worsening depression and suicidal thoughts 1
• Respiratory compromise: Use caution in asthma, COPD, or sleep apnea 1
• Cognitive impairment or dementia: Observational data link hypnotics to increased dementia risk (HR 2.34) 1

Critical Safety Warnings

Complex Sleep Behaviors

All patients must be warned about potentially life-threatening complex sleep behaviors including sleep-driving, sleep-walking, and sleep-eating; discontinue eszopiclone immediately if these occur. 1, 2

• Reported with all benzodiazepine receptor agonists 1
• Patients have no recollection of these activities 1
• Risk increased with alcohol use, other CNS depressants, or doses exceeding recommended amounts 1

Next-Day Impairment

• Driving impairment: Eszopiclone 3 mg produces measurable psychomotor and memory deficits up to 11.5 hours after dosing 2
• Patients often do not perceive the impairment 2
• FDA warning: Avoid driving or operating machinery until fully awake 1, 2
• Women and elderly require lower doses due to cognitive and behavioral changes 1

Falls and Fractures

• Increased risk in all patients, especially elderly (≥65 years) 1, 2
• Observational studies link hypnotic use to fractures, major injuries, and possibly dementia 1, 2

Drug Interactions

• Alcohol: Avoid completely—markedly increases risk of complex sleep behaviors and respiratory depression 1, 2
• Other CNS depressants: Additive psychomotor impairment; avoid combining multiple sedatives 1, 2
• CYP3A4 inhibitors: May increase eszopiclone levels, though clinically significant interactions are uncommon 3

Efficacy Data

Sleep Parameters

• Sleep onset latency: Reduced by 19 minutes vs placebo 1
• Total sleep time: Increased by 28–57 minutes (dose-dependent: 2 mg = 28 min, 3 mg = 45–57 min) 1
• Wake after sleep onset: Reduced by 11 minutes 1
• Sleep quality: Moderate-to-large improvement in subjective sleep quality 1

Clinical Response

• Remission rate (ISI <7): 50% with eszopiclone vs 19% with placebo at 12 weeks 1
• Objective sleep efficiency: Clinically significant improvement on polysomnography 1
• Daytime functioning: Improved next-day alertness and reduced napping in elderly patients 6

Treatment Algorithm

1. Initiate Cognitive Behavioral Therapy for Insomnia (CBT-I) first—this is mandatory before or alongside any pharmacotherapy. 1, 2

• CBT-I provides superior long-term efficacy with sustained benefits after medication discontinuation 1, 2
• Includes stimulus control, sleep restriction, relaxation techniques, and cognitive restructuring 1, 2

2. Add eszopiclone only if CBT-I is insufficient or unavailable after 4–8 weeks. 1, 2

3. Start with appropriate dose based on age and hepatic function:

• Adults 18–64 years: 2 mg 1
• Elderly ≥65 years: 1 mg 1
• Hepatic impairment: 1 mg 1

4. Reassess after 1–2 weeks:

• Evaluate sleep onset latency, total sleep time, nocturnal awakenings, and daytime functioning 1, 2
• Monitor for adverse effects: unpleasant taste (most common), somnolence, headache, memory impairment 1, 3
• Screen for complex sleep behaviors at every visit 1, 2

5. Titrate if needed:

• Adults: Increase to 3 mg if 2 mg is tolerated but insufficient 1
• Elderly: Increase to 2 mg maximum if 1 mg is insufficient 1

6. Plan for discontinuation:

• Taper gradually to avoid rebound insomnia 2, 3
• Use CBT-I to facilitate successful cessation 2
• Reassess every 2–4 weeks for ongoing need 1, 2

Common Pitfalls to Avoid

• Starting pharmacotherapy without CBT-I: Leads to less durable benefit and higher relapse rates 1, 2
• Using adult dosing in elderly patients: Must reduce to maximum 2 mg to minimize fall risk 1, 2
• Combining with alcohol or multiple sedatives: Dramatically increases risk of respiratory depression, complex sleep behaviors, and cognitive impairment 1, 2
• Failing to reassess regularly: Efficacy, side effects, and continued need must be evaluated every 2–4 weeks 1, 2
• Continuing long-term without periodic drug holidays: Consider tapering after 3–6 months if effective 2
• Ignoring persistent insomnia beyond 7–10 days: Evaluate for underlying sleep disorders (sleep apnea, restless legs syndrome, circadian rhythm disorders) 1, 2

Adverse Effects Profile

Most Common (from clinical trials)

• Unpleasant or bitter taste (most frequent) 1, 3
• Headache 1, 3
• Somnolence 1
• Dry mouth 3
• Dizziness 3

Serious Adverse Events

• Complex sleep behaviors 1
• Memory impairment 1
• Depression and anxiety 1
• Accidental injury 1, 3
• Serious adverse events leading to withdrawal: 2–3% 1

Withdrawal Effects (upon discontinuation)

• Anxiety, abnormal dreams, hyperesthesia, nausea, upset stomach 3
• Rebound insomnia possible with 2 mg dose 3
• No serious withdrawal effects or dependence in 12-month trials 4, 5, 3

Special Populations

Women

• FDA recommends dose reduction due to cognitive and behavioral changes 1
• Consider starting at 1–2 mg rather than 3 mg 1

Patients with Substance Use History

• Eszopiclone 6–12 mg produces euphoria similar to diazepam 20 mg in benzodiazepine addicts 3
• Consider ramelteon (no abuse potential) as alternative 2
• If eszopiclone used, prescribe smallest quantities and monitor closely 2