AHFS Class:

• Non-benzodiazepine Hypnotics 28:24.44

Generic Name(s):

• Eszopiclone

Eszopiclone, the S -enantiomer of zopiclone (not commercially available in the US), is a sedative and hypnotic agent structurally unrelated to the benzodiazepines.1,2,3,5,10,11

Insomnia

Eszopiclone is used as a hypnotic agent in the management of transient and chronic insomnia.1,2,3,11 In controlled clinical studies, eszopiclone reportedly has been shown to have continued efficacy in decreasing sleep latency, improving sleep maintenance, and prolonging total sleep time when administered nightly for periods up to 6 months in duration.1,2,3

Clinical Experience

Efficacy of eszopiclone for the management of transient insomnia was established in a controlled study in adults experiencing such insomnia during the first night in a sleep laboratory.1,2,5 In this study, 2- and 3-mg doses of eszopiclone were superior to placebo on the polysomnographic parameters of latency to persistent sleep (LPS) and wake time after sleep onset (WASO).1,2,5 Individuals receiving the 3-mg dose, but not those receiving the 2-mg dose, experienced substantially fewer awakenings than did individuals receiving placebo.5 Residual daytime psychomotor and/or cognitive impairment, as rated on a visual analog scale for morning sleepiness and assessed objectively using the Digit Symbol Substitution test (DSST), appeared to be minimal at eszopiclone doses of ≤3 mg.5 At such doses, sleep architecture (i.e., the percentage of time spent in each sleep stage) generally was preserved.5

Efficacy of eszopiclone for the management of chronic insomnia was established in 5 controlled studies of up to 6 months' duration, including 3 studies in adults and 2 in geriatric patients.1,3,12 Results of these studies indicate that usual doses of eszopiclone (i.e., 2-3 mg in adults and 1-2 mg in geriatric patients) substantially decrease sleep latency;1,2,3,12 however, only the 3-mg dose in adults and the 2-mg dose in geriatric patients were superior to placebo on measures of sleep maintenance (e.g., WASO).1,2,12 Pharmacodynamic tolerance and adaptation to the hypnotic effect of eszopiclone were not observed during 6 months of therapy with the drug.1,2,3,12 Evidence to suggest, however, that such sleep improvements are maintained following discontinuance of eszopiclone is currently lacking.13

Clinical Perspective

The American Academy of Sleep Medicine (AASM) and the American College of Physicians (ACP) have published clinical guidelines for the treatment of insomnia in adults.204,205,206 According to these guidelines, the goals of insomnia treatment are to improve sleep quality and quantity and to reduce insomnia-related daytime impairment, distress, and dysfunction.204,206 When possible, psychological and behavioral interventions are recommended as initial treatment.204,205,206 Pharmacologic therapy should be considered mainly in patients who are unable or unwilling to participate in cognitive behavioral therapy, are unresponsive to such therapy, or, in select cases, as a temporary adjunct to such therapy.205 When pharmacologic therapy is indicated, the choice of agent should be directed by symptoms, treatment goals, past treatment response, patient preference, drug cost and availability, comorbid conditions/contraindications, concomitant drug therapy/interactions, and potential adverse effects.204,205 Data on comparative efficacy of various sedative-hypnotic agents are limited, and an individualized and shared decision-making approach between patients and clinicians is advised.205,206

Eszopiclone is among several agents recommended for the treatment of sleep onset and sleep maintenance insomnia.204,205,206 Pharmacologic therapy should be administered at the lowest effective dosage and should be short-term (e.g., 4-5 weeks) in duration;204,206 chronic use should be reserved for those individuals for whom cognitive behavioral therapy is either inaccessible or ineffective, who have been appropriately screened for contraindications to such treatment, who maintain long-term benefits with medication, and who are followed regularly.205 Patient monitoring should include ongoing assessment of effectiveness, monitoring for adverse effects, and evaluation for new onset or exacerbation of existing comorbid disorders.204

General

Pretreatment Screening

• Screen patients for diseases or conditions that may affect drug metabolism or hemodynamic responses.1
• Consider the risk of respiratory depression prior to use of eszopiclone in patients with respiratory impairment.1
• Screen patients for signs and symptoms of depression.1
• Screen patients for a history of alcohol or drug abuse or psychiatric disorders.1

Patient Monitoring

• Monitor for excess CNS depressant effects.1
• Reevaluate patient if insomnia persists after 7-10 days of treatment.1
• Carefully evaluate any new behavioral sign or symptom of concern.1
• Closely monitor patients with a history of alcohol or drug abuse or psychiatric disorders.1

Administration

Eszopiclone is administered orally at bedtime.1 The drug should be taken immediately before retiring and only when the patient is able to get 7-8 hours of sleep before it is necessary to be active again.1

Eszopiclone should not be administered with or immediately after a meal; administration with or immediately after a heavy, high-fat meal results in a decreased rate of absorption of eszopiclone and would be expected to decrease the drug's effect on sleep latency.1

Dosage

Dosage of eszopiclone should be individualized, and the lowest effective dosage should be used in all patient populations.1

For the management of insomnia, the recommended initial adult dosage of eszopiclone is 1 mg immediately before bedtime.1 The recommended initial dosage is the same for women and men.15 If clinically indicated, dosage may be increased to 2 or 3 mg immediately before bedtime.1

The dosage range of 2-3 mg has been shown to be effective in decreasing sleep latency and improving measures of sleep maintenance in adults <65 years of age.1 However, in some patients, the 2- or 3-mg dose may produce higher morning blood concentrations of eszopiclone, resulting in an increased risk of next-day impairment of driving and other activities that require full alertness.1 The adult dosage of eszopiclone should not exceed 3 mg immediately before bedtime.1

Special Populations

In geriatric or debilitated patients, the recommended initial dosage of eszopiclone is 1 mg immediately before bedtime.1 If clinically indicated, dosage may be increased to 2 mg immediately before bedtime.1 The dosage range of 1-2 mg has been shown to be effective in decreasing sleep latency and improving measures of sleep maintenance in geriatric patients.1 Dosage of eszopiclone in geriatric or debilitated patients should not exceed 2 mg immediately before bedtime.1

In patients receiving a potent inhibitor of cytochrome P-450 (CYP) isoenzyme 3A4, dosage of eszopiclone should not exceed 2 mg immediately before bedtime.1

Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment.1 However, in patients with severe hepatic impairment, dosage of eszopiclone should not exceed 2 mg immediately before bedtime.1

No eszopiclone dosage adjustment is necessary in patients with renal impairment.1

Contraindications

• History of a complex sleep behavior while taking eszopiclone, zaleplon, or zolpidem.1,200
• Known hypersensitivity (e.g., anaphylaxis, angioedema) to eszopiclone or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Complex Sleep Behaviors

Complex sleep behaviors such as sleepwalking, sleep driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), and engaging in other activities (e.g., making phone calls, preparing and eating food) while not fully awake have been reported in patients receiving sedative and hypnotic drugs.1,200,201,202,203 A boxed warning about the risk of complex sleep behaviors is included in the prescribing information for eszopiclone.1 Such complex sleep behaviors can result in serious injury and/or death.1,200 Complex sleep behaviors appear to be more common with eszopiclone, zaleplon, and zolpidem than other prescription medicines used for sleep.200 Patients usually have no memory of the events.1 These behaviors may occur when eszopiclone is used alone at recommended doses or when used concomitantly with alcohol or other CNS depressants.1,200 Serious injuries and fatalities from complex sleep behaviors have occurred in patients with and without a history of such behaviors and can occur even at the lowest recommended dosages and after just one dose of the hypnotic agent.200 Discontinue eszopiclone immediately in patients who experience a complex sleep behavior.1,200

A total of 66 cases of complex sleep behaviors resulting in serious injuries or death in patients who took eszopiclone, zaleplon, or zolpidem were reported to the FDA Adverse Event Reporting System (FAERS) database and/or in published literature between December 1992 and March 2018.200,201,202,203 Of the 66 cases, 20 were reported as resulting in fatal outcomes and 46 reported serious nonfatal injuries; in the nonfatal cases, patients usually did not remember experiencing these complex sleep behaviors.200 These cases included falls with serious injuries such as intracranial hemorrhages, vertebral fractures, and hip fractures as well as fatal falls, self-injuries, accidental overdoses, hypothermia, suicide attempts and apparent completed suicides, fatal motor vehicle collisions, gunshot wounds, carbon monoxide poisoning, drowning or near drowning, burns, and homicide.200,201,202,203 Most of the patients in these cases reported using zolpidem (about 92%) when they experienced the complex sleep behavior; the remaining patients took eszopiclone (about 5%) or zaleplon (about 3%), reflecting the higher number of zolpidem prescriptions that were dispensed over this period compared with eszopiclone and zaleplon.200 The underlying mechanisms by which these drugs cause complex sleep behaviors are not fully understood.200

Other Warnings and Precautions

Hypersensitivity Reactions

Angioedema involving the tongue, glottis, or larynx has occurred rarely following initial or subsequent doses of sedative and hypnotic drugs, including eszopiclone; airway obstruction may occur and may be fatal.1 Other symptoms suggestive of anaphylaxis (e.g., dyspnea, throat closing, nausea, vomiting) also have occurred.1 Medical therapy in the emergency department has been required in some patients.1

Patients who develop angioedema following treatment with eszopiclone should not be rechallenged with the drug.1

CNS Depressant Effects and Next-day Impairment

CNS depressant effects (i.e., memory impairment, confusion) have been reported in patients receiving higher doses of eszopiclone.1 In clinical studies evaluating CNS depressant effects of eszopiclone doses of 2-3 mg in adults, memory impairment was reported in 1-1.3% of patients receiving eszopiclone compared with 0% of those receiving placebo, and confusion was reported in 3% of patients receiving eszopiclone compared with 0% of those receiving placebo.1 In clinical studies evaluating CNS depressant effects of eszopiclone 2 mg in geriatric patients, memory impairment was reported in 1.5% of patients receiving eszopiclone compared with 0% of those receiving placebo, and confusion was reported in 2.5% of patients receiving eszopiclone compared with 0% of those receiving placebo.1

Drowsiness and decreased levels of consciousness associated with eszopiclone may increase the risk of falls, particularly in geriatric patients.1

Next-day impairment of psychomotor function has been reported in patients receiving the 3-mg dose of eszopiclone.1 In a study in 91 healthy individuals, treatment with eszopiclone 3 mg at bedtime was associated with next-morning impairment of psychomotor function (i.e., ability to maintain a motor vehicle in the driving lane, working memory, motor coordination); such impairment was most severe at 7.5 hours postdose but was still present and potentially clinically meaningful at 11.5 hours postdose.1 Patients often were unaware of these impairments.1,15

The risk of next-day psychomotor impairment is increased if eszopiclone is administered with less than 7-8 hours of sleep time remaining.1 The risk of next-day impairment also is increased if a higher than recommended dose of eszopiclone is administered or when eszopiclone is used concomitantly with other CNS depressants or with drugs capable of increasing eszopiclone concentrations.1

To reduce the potential risk of next-day impairment, the manufacturer and FDA have lowered the recommended initial dosage of eszopiclone from 2 mg to 1 mg immediately before bedtime.1,15 Women and men are equally susceptible to impairment from eszopiclone; therefore, the recommended initial dosage (1 mg immediately before bedtime) is the same for women and men.15 This lower initial dosage will result in less drug in the blood the next day.1,15 FDA states that patients currently receiving eszopiclone should continue therapy at the prescribed dosage and should contact their clinician to determine the most appropriate dosage.15 FDA is continuing to evaluate the risk of impaired mental alertness associated with other sedative and hypnotic drugs, including nonprescription (over-the-counter, OTC) preparations, and will update the public as new information becomes available.15 The agency states that nonprescription sedative and hypnotic drugs should not be considered safer than prescription drugs.15

Patients receiving eszopiclone should be monitored for excessive CNS depressant effects; however, impairment may occur in the absence of symptoms and may not be reliably detected by ordinary clinical examination (i.e., formal psychomotor testing may be required).1 Patients receiving the 3-mg dose should be cautioned against driving or engaging in other activities that require complete mental alertness the day after use.1,15

Concomitant use of eszopiclone with other CNS depressants (e.g., alcohol, benzodiazepines, opiates, tricyclic antidepressants) results in additive CNS depression.1 Concomitant use of eszopiclone with other sedative and hypnotic drugs, including OTC preparations used to treat insomnia (e.g., diphenhydramine, doxylamine succinate), at bedtime or in the middle of the night is not recommended.1,200

Adequate Patient Evaluation

Because sleep disturbances may be a manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after careful evaluation of the patient.1 Failure of insomnia to remit after 7-10 days of eszopiclone therapy, worsening of insomnia, or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric, physical, and/or medical condition that requires evaluation; patients should be reevaluated if insomnia persists after 7-10 days of therapy.1

Abnormal Thinking and Behavioral Changes

Abnormal thinking and behavioral changes have been reported in patients receiving sedative and hypnotic drugs.1 Some of these changes are similar to manifestations of alcohol intoxication or effects associated with other CNS depressants and include decreased inhibition (e.g., aggressiveness and extroversion that seem out of character), bizarre behavior, agitation, depersonalization, and hallucinations.1 Amnesia and other neuropsychiatric symptoms may occur unpredictably.1

It can rarely be determined with certainty whether a particular instance of the abnormal behavior is drug induced, spontaneous, or results from an underlying psychiatric or physical disorder.1 Nevertheless, the emergence of any new behavioral sign or symptom of concern in patients receiving eszopiclone requires careful and immediate evaluation.1

Withdrawal Effects

Manifestations of withdrawal have been reported following abrupt discontinuance or rapid reduction in dosage of sedative and hypnotic drugs.1,3 Clinical trials of eszopiclone did not reveal evidence of a serious withdrawal syndrome;1,3 however, anxiety, abnormal dreams, nausea, upset stomach, hyperesthesia, and neurosis were reported at an incidence of ≤2% after placebo substitution within 48 hours following the last dose of eszopiclone.1

Rebound insomnia of 1 day's duration was noted in controlled trials of eszopiclone.1

Abuse Potential

Studies using relatively high eszopiclone dosages (e.g., 2-4 times the maximum recommended hypnotic dosage) in individuals with a history of benzodiazepine abuse suggest that the abuse potential of eszopiclone is similar to that of benzodiazepines (e.g., diazepam); caution is advised in patients with a history of drug or alcohol abuse or a history of psychiatric disorders.1

Tolerance

Pharmacodynamic tolerance and adaptation to the hypnotic effect of eszopiclone were not observed during studies of up to 6 months' duration.1,2,3

Timing of Drug Doses

Ingesting eszopiclone while still up and about could result in adverse CNS effects such as short-term memory impairment, hallucinations, dizziness, and impaired coordination.1 Therefore, eszopiclone should be administered immediately before retiring.1

Geriatric and/or Debilitated Patients

Geriatric and/or debilitated patients may be more sensitive to pharmacologic and adverse effects (e.g., impaired motor and/or cognitive performance) of sedative and hypnotic agents; reduction of the maximum dosage is recommended in such patients.1,13

Concomitant Diseases

Experience in patients with concomitant disease is limited; eszopiclone should be used with caution in patients with diseases that may affect metabolism or hemodynamic responses.1

Although respiratory depression was not reported in healthy individuals receiving doses 2.5-fold higher than the recommended dose,1 caution is advised in patients with impaired respiratory function.1

Use in Patients with Depression

Worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported in primarily depressed patients receiving sedative and hypnotic drugs.1

As with other sedative and hypnotic agents, eszopiclone should be used with caution in patients with depression.1 Suicidal tendencies may be present, and protective measures may be required.1 Intentional overdosage is more common in this patient population, and the least amount of drug feasible should be prescribed and dispensed at any one time to avoid such intentional overdosage.1

Specific Populations

Pregnancy

Available pharmacovigilance data on use of eszopiclone in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 There was no evidence of teratogenicity in animal reproduction studies in pregnant rats and rabbits administered eszopiclone throughout organogenesis.1 Administration of eszopiclone to rats throughout pregnancy and lactation resulted in offspring toxicities at all doses tested, with the lowest dose being approximately 200 times the maximum recommended human dose of 3 mg daily based on body surface area.1

Lactation

It is not known whether eszopiclone is distributed into milk, affects the breast-fed infant, or affects milk production.1 Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for eszopiclone and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1

Pediatric Use

Safety and efficacy of eszopiclone have not been established in pediatric patients.1

Eszopiclone has not been shown to be effective in the management of insomnia associated with attention deficit hyperactivity disorder (ADHD).1 In a 12-week controlled study in 483 pediatric patients (6-17 years of age) with insomnia associated with ADHD, eszopiclone (1, 2, or 3 mg at bedtime) did not decrease sleep latency as compared with placebo.1 In this study, the most frequent treatment-emergent adverse effects (compared with placebo) were psychiatric and nervous system effects, including dysgeusia (9 versus 1%), dizziness (6 versus 2%), hallucinations (2 versus 0%), and suicidal ideation (0.3 versus 0%).1 Discontinuance of therapy was required in 3% of patients receiving eszopiclone and in 2% of those receiving placebo.1

Geriatric Use

In clinical studies, a total of 287 patients randomized to receive eszopiclone were 65 years of age or older (range: 65-86 years).1 The adverse effect profile of the 2-mg dose in geriatric patients (median age: 71 years) was similar to that observed in clinical trials of the drug in younger adults.1 However, patients ≥65 years of age had a longer elimination half-life and higher total systemic exposure to eszopiclone compared with younger adults.1 Reduction of the maximum dosage is recommended because of impaired motor and cognitive performance as well as increased sensitivity in geriatric patients.1

Hepatic Impairment

Systemic exposure to eszopiclone is increased twofold in patients with severe hepatic impairment compared with healthy individuals.1

Eszopiclone should be used with caution in patients with hepatic impairment.1 Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment; however, reduction of the maximum dosage is recommended in those with severe hepatic impairment.1

Renal Impairment

No dosage adjustment appears necessary in patients with renal impairment, since <10% of an oral dose of eszopiclone is excreted unchanged in urine.1

Common Adverse Effects

Adverse effects reported in ≥2% of patients receiving eszopiclone include unpleasant taste, headache, somnolence, respiratory infection, dizziness, dry mouth, rash, and viral infection.1

Eszopiclone is metabolized principally by cytochrome P-450 (CYP) isoenzymes 3A4 and 2E1; the drug does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4.1 Eszopiclone is not expected to alter the clearance of drugs that are metabolized by common CYP isoenzymes.1

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4

Concomitant use of eszopiclone with inhibitors of CYP3A4 may result in increased systemic exposure to eszopiclone.1 When the potent CYP3A4 inhibitor ketoconazole (400 mg daily for 5 days) was administered concomitantly with eszopiclone (3 mg at bedtime), eszopiclone exposure, peak plasma concentration, and half-life were increased by 2.2-, 1.4-, and 1.3-fold, respectively.1

If eszopiclone is used concomitantly with a potent CYP3A4 inhibitor (e.g., clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), dosage of eszopiclone should not exceed 2 mg once daily immediately before bedtime.1

Inducers of CYP3A4

Concomitant use of eszopiclone with inducers of CYP3A4 may result in decreased systemic exposure to and efficacy of eszopiclone.1 When zopiclone (not commercially available in the US) was administered concomitantly with the potent CYP3A4 inducer rifampin, exposure to zopiclone was decreased by 80%; a similar effect would be expected with eszopiclone.1

CNS-active Drugs

When eszopiclone was administered concomitantly with olanzapine, no alteration in the pharmacokinetics of either drug was observed; however, a pharmacodynamic interaction (effect on psychomotor function, as manifested by a decrease in Digit Symbol Substitution test [DSST] scores) was noted.1

When eszopiclone (single dose) was administered concomitantly with paroxetine, no pharmacokinetic or pharmacodynamic interactions were observed; however, the possibility of a pharmacodynamic interaction between the drugs following long-term concomitant use cannot be ruled out.1

CNS Depressants

Concomitant use of eszopiclone with other CNS depressants (e.g., alcohol, benzodiazepines, opiates, sedatives and hypnotics, tricyclic antidepressants) may result in additive CNS depression.1,200 Concomitant use of alcohol with eszopiclone results in additive psychomotor impairment.1 Although no clinically important pharmacokinetic or pharmacodynamic interaction was observed following single-dose administration of eszopiclone with lorazepam, the possibility of a pharmacodynamic interaction between the drugs following long-term concomitant use cannot be ruled out.1

Concomitant use of eszopiclone with alcohol should be avoided.1 Concurrent use of other sedative and hypnotic drugs used to treat insomnia (including OTC preparations such as diphenhydramine and doxylamine succinate) should also be avoided in patients receiving eszopiclone.200 When eszopiclone is used concomitantly with other CNS depressants, dosage reduction of eszopiclone and the CNS depressant may be necessary.1

Digoxin

The pharmacokinetics of digoxin were not affected following concomitant administration of eszopiclone (single 3-mg dose) with digoxin (0.5 mg twice daily for 1 day, followed by 0.25 mg daily for 6 days).1

Protein-bound Drugs

Because eszopiclone is not highly bound (52-59%) to plasma proteins, concomitant use of eszopiclone with highly protein-bound drugs is not expected to affect the free concentration of either drug.1

Warfarin

Concomitant administration of eszopiclone (3 mg daily for 5 days) with warfarin (single 25-mg dose) in healthy individuals did not affect the pharmacokinetics of R - or S -warfarin, nor were there any changes in the pharmacodynamic profile (prothrombin time).1,13

Description

Eszopiclone, the S -enantiomer of zopiclone (not commercially available in the US), is a sedative and hypnotic agent that is structurally unrelated to benzodiazepines and other sedative and hypnotic agents that are commercially available in the US, including barbiturates, imidazopyridines (e.g., zolpidem), and pyrazolopyrimidines (e.g., zaleplon).1,2,3,5,10 Eszopiclone is pharmacologically similar to zaleplon and zolpidem; all of these agents have been shown to interact with the CNS γ-aminobutyric acid (GABA_A) receptor complex at binding domains located close to or allosterically coupled to benzodiazepine receptors.1,2,10,11 In vitro binding affinity of eszopiclone for benzodiazepine receptors is about 50 times that of the R -enantiomer of zopiclone.2,10 Preclinical data suggest that most, if not all, of the hypnotic effects of racemic zopiclone are attributable to the S -enantiomer.3,10 However, further studies are needed to determine whether these differences result in any clinical superiority of eszopiclone compared with zopiclone.2,13

Eszopiclone is rapidly absorbed from the GI tract following oral administration.1,2,3,4 Eszopiclone has an intermediate duration of action (i.e., possesses a half-life of approximately 5-7 hours).1,2,3,4,9 Following oral administration, eszopiclone is extensively metabolized to several active and inactive metabolites via demethylation and oxidation by the cytochrome P-450 (CYP) 3A4 and 2E1 isoenzymes.1,2 Eszopiclone does not appear to have any inhibitory effect on CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4.1

Advice to Patients

• Provide patient with a copy of manufacturer's patient information.1 Advise patients to read the manufacturer's medication guide carefully prior to initiating therapy and each time the prescription is refilled.1
• Instruct patients to administer the drug immediately before retiring.1
• Instruct patients to take eszopiclone only when able to get a full night's sleep (i.e., 7-8 hours) before being active again.1
• Advise patients to avoid taking eszopiclone with or immediately after a meal.1
• Advise patients to take the drug only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.1
• Advise patients to contact their clinician if their insomnia worsens or does not improve within 7-10 days of treatment.1
• Advise patients to avoid taking eszopiclone if alcohol has been consumed in the evening or before bedtime.1 Advise patients to avoid concurrent use of other sedative and hypnotic drugs used to treat insomnia (including OTC preparations such as diphenhydramine or doxylamine succinate) or CNS depressants during therapy, unless otherwise instructed by a clinician.1,200
• Risk of serious injury and/or death resulting from complex sleep behaviors (e.g., sleep-walking, sleep-driving, preparing and eating food, making phone calls, or having sex while not being fully awake).1,200 Advise patients to discontinue eszopiclone and notify a clinician immediately if an episode of complex sleep behavior occurs during therapy, even if it did not result in a serious injury.1,200
• Risk of next-day impairment, even when used as prescribed; impairment may be present despite feeling fully awake.1,15 Advise patients to exercise caution when operating machinery or performing hazardous tasks while using eszopiclone and to avoid these activities until they feel fully awake.1 Advise patients receiving the 3-mg dose to avoid driving or engaging in other activities that require complete mental alertness the day after use.1,15
• Advise patients that drowsiness and decreased consciousness may increase the risk of falls in some patients.1
• Risk of severe anaphylactic and anaphylactoid reactions; instruct patients to seek immediate medical attention if hypersensitivity reactions occur.1
• Risk of abnormal thinking, behavioral changes, memory loss, and anxiety.1 Instruct patients to contact a clinician immediately if these adverse effects occur.1
• Advise patients to immediately report any suicidal thoughts.1
• Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as concomitant or past illnesses (e.g., depression, substance abuse).1
• Instruct women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.1
• Inform patients of other important precautionary information.1 (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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