What are the complications associated with daily use of Lunesta (eszopiclone)?

Complications Associated with Daily Use of Lunesta (Eszopiclone)

Daily use of Lunesta (eszopiclone) carries significant risks including CNS depression with next-day impairment, complex sleep behaviors, potential for dependence and tolerance, and cognitive effects, though unlike most hypnotics, eszopiclone has no FDA-mandated short-term usage restriction. 1, 2

CNS Depression and Next-Day Impairment

• Eszopiclone impairs daytime function in some patients at higher doses (2-3 mg), even when used as prescribed, and this impairment may occur without subjective symptoms. 2
• Patients using 3 mg should be cautioned against driving or engaging in hazardous activities the day after use, as pharmacodynamic tolerance may not develop to all depressant effects. 2
• The risk of next-day psychomotor impairment increases if taken with less than 7-8 hours of sleep remaining, at doses higher than recommended, or when combined with other CNS depressants. 2
• Additive effects occur with concomitant use of benzodiazepines, opioids, tricyclic antidepressants, and alcohol, requiring downward dose adjustment of both eszopiclone and the concomitant CNS depressant. 2

Complex Sleep Behaviors and Psychiatric Effects

• Complex behaviors including "sleep-driving" (driving while not fully awake with amnesia for the event) have been reported and can occur at therapeutic doses. 2
• The FDA has issued warnings regarding disruptive sleep-related behaviors including sleepwalking, eating, driving, and sexual behavior with benzodiazepine receptor agonist hypnotics. 1
• The risk of these behaviors increases with alcohol use, other CNS depressants, and doses exceeding the maximum recommended dose. 1, 2
• Abnormal thinking and behavioral changes including decreased inhibition, aggressiveness, bizarre behavior, agitation, hallucinations, and depersonalization have been reported. 2
• Amnesia and other neuropsychiatric symptoms may occur unpredictably, and in depressed patients, worsening of depression including suicidal thoughts has been reported. 2

Dependence, Tolerance, and Withdrawal

• Eszopiclone is a Schedule IV controlled substance with abuse potential similar to benzodiazepines. 2
• In abuse liability studies, eszopiclone at 6 and 12 mg (2-4 times the maximum recommended dose) produced euphoric effects similar to diazepam 20 mg in individuals with histories of benzodiazepine abuse. 2, 3
• The risk of dependence increases with dose, duration of treatment, and concomitant use of other psychoactive drugs, particularly in patients with a history of alcohol/drug abuse or psychiatric disorders. 2
• Withdrawal symptoms following discontinuation include anxiety, abnormal dreams, nausea, and upset stomach, though these occurred at an incidence of 2% or less in clinical trials. 2, 3
• Rebound insomnia following withdrawal of 2 mg doses has been documented in non-elderly subjects. 3
• However, studies up to 12 months showed no evidence of tolerance to sleep parameters, distinguishing eszopiclone from many other hypnotics. 1, 4, 5, 3

Common Adverse Effects

• The most common side effects include unpleasant or bitter taste (metallic taste), headache, dyspepsia, diarrhea, dry mouth, and dizziness. 4, 3
• Upper respiratory infection, urinary tract infection, pain, and accidental injury have also been reported. 3
• Memory impairment, particularly during the first few hours after administration, can occur. 6

Serious Safety Concerns

• Rare cases of angioedema involving the tongue, glottis, or larynx have been reported, which can be fatal if airway obstruction occurs. 2
• Some patients experienced additional symptoms suggesting anaphylaxis including dyspnea, throat closing, nausea, and vomiting requiring emergency department treatment. 2
• Patients who develop angioedema should never be rechallenged with eszopiclone. 2

Special Population Considerations

• Elderly or debilitated patients should receive reduced doses (maximum 2 mg) due to increased sensitivity. 1
• Patients with severe hepatic impairment should not exceed 2 mg daily. 1
• The elimination half-life increases from 6 hours in younger adults to approximately 9 hours in patients 65 years or older, increasing the risk of next-day effects. 3

Clinical Monitoring Recommendations

• Caution is advised in patients with signs/symptoms of depression, compromised respiratory function (asthma, COPD, sleep apnea), or hepatic/heart failure. 1
• Administration on an empty stomach is advised to maximize effectiveness. 1
• Not recommended during pregnancy or nursing. 1
• The failure of insomnia to remit after 7-10 days of treatment may indicate a primary psychiatric or medical illness requiring evaluation. 2
• Worsening of insomnia or emergence of new thinking/behavior abnormalities should prompt reassessment for unrecognized psychiatric or physical disorders. 2