AHFS Class:

• Non-benzodiazepine Hypnotics 28:24.44

Generic Name(s):

• Zaleplon

Zaleplon, a pyrazolopyrimidine derivative, is a sedative and hypnotic agent structurally unrelated to the benzodiazepines and other sedative-hypnotic agents.1,2,3,4,12,13,18

Insomnia

Zaleplon is used in the short-term management of insomnia.1,2,12,13,14,15,16,18,19 Zaleplon has been shown to decrease sleep latency with repeated use for periods up to 30 days in duration.1,2,12,13,14,15,16,18,19 Because of the drug's short half-life, clinical studies have focused on decreasing sleep latency.1,2,12,15,18,19 Zaleplon has not been shown to substantially increase total sleep time or decrease the number of awakenings,1,3,18 and therefore appears to be most useful for sleep initiation disorders.3,12

Clinical Experience

Efficacy of zaleplon for the treatment of transient insomnia was established in a controlled study in adults experiencing insomnia during the first night in a sleep laboratory; a 10-mg but not a 5-mg dose of zaleplon was superior to placebo in this patient population.1

Efficacy for the treatment of chronic insomnia in adults was established in 9 controlled studies of 1-35 days' duration.1,2,12,14,15,18 The clinical efficacy trials ranged from a single night to 5 weeks in duration; the final formal assessments of sleep latency were performed at the end of treatment.1 The 10- and 20-mg doses of zaleplon were superior to placebo in decreasing sleep latency; some studies demonstrated efficacy versus placebo throughout the study, while others had a substantial number of placebo responders resulting in only 2 days' duration of superior efficacy for zaleplon.1,2,12,14,15,18 Although both the 10- and 20-mg doses were effective, the therapeutic effect was greater and more consistent with the 20-mg dose, and the 5-mg dose was less consistently effective.1,2,14,15 In one study, 10-mg doses of zaleplon were shown to have continued efficacy when administered for at least 30 consecutive nights.1 However, failure of insomnia to remit after 7-10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated.1 Insomnia may be the primary or first symptom of an unrecognized psychiatric and/or physical disorder.1,24

Efficacy for the treatment of chronic initial insomnia in geriatric patients was established in 3 controlled studies of 2-14 days' duration in which 5- and 10-mg doses were shown to be superior to placebo in decreasing sleep latency.1,19

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

Zaleplon is among several agents recommended for the treatment of sleep onset insomnia.204,205 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; use zaleplon with caution in such patients.1
• Consider the risk of respiratory depression prior to use of zaleplon in patients with respiratory impairment, including those with sleep apnea or chronic obstructive pulmonary disease.1
• Screen patients for a history of addiction to, or abuse of, drugs or alcohol.1

Patient Monitoring

• Monitor for abnormal thinking and behavioral changes; carefully and immediately evaluate any new and concerning behavioral sign or symptom.1
• Monitor geriatric and/or debilitated patients closely for adverse effects.1
• Monitor patients with a history of addiction to, or abuse of, drugs or alcohol closely for zaleplon habituation and dependence.1

Administration

Zaleplon is administered orally without regard to meals, although administration with a high-fat meal should be avoided because of a potential decreased rate of drug absorption.1 Such delay in GI absorption could result in decreased efficacy on sleep latency.1

Because of its rapid onset of action, zaleplon should be taken immediately before retiring when the patient is ready to go to sleep or after the patient has already gone to bed but has experienced difficulty falling asleep.1 Patients should be advised that zaleplon should only be used in circumstances where they are able to get a full night's sleep.1

Dosage

Dosage of zaleplon should be individualized.1 The lowest effective dosage of the drug should be used in all patient populations.1,200

The recommended initial dosage of zaleplon for the management of insomnia in most adults <65 years of age is 10 mg immediately before bedtime or after unsuccessfully attempting to sleep.1 Although the risk of certain adverse effects appears to be dose dependent, 20-mg doses have been shown to be adequately tolerated and may be considered in most adults who do not respond adequately to lower doses.1 Doses >20 mg have not been adequately studied and are not recommended by the manufacturer.1

Special Populations

Hepatic Impairment

Patients with mild to moderate hepatic impairment should receive the 5-mg zaleplon dosage since drug clearance is reduced in these patients.1 Zaleplon is not recommended for use in patients with severe hepatic impairment.1

Renal Impairment

No zaleplon dosage adjustment is necessary in patients with mild to moderate renal impairment; zaleplon has not been adequately studied in patients with severe renal impairment.1

Geriatric and/or Debilitated Patients

For geriatric adults ≥65 years of age and debilitated patients, 5-mg doses of zaleplon are recommended.1 Doses >10 mg are not recommended in these populations.1

Low-weight Patients

For certain low-weight nongeriatric adults, 5-mg doses of zaleplon may be sufficient.1

Japanese Patients

Japanese adults demonstrated pharmacokinetic parameter differences that potentially could be explained by differences in body weight or hepatic enzyme activity.1

Patients Receiving Cimetidine

Patients receiving cimetidine concomitantly should receive the 5-mg zaleplon dosage since drug clearance is reduced in these patients.1

Contraindications

• Hypersensitivity to zaleplon or any ingredient in the formulation.1
• History of a complex sleep behavior while taking eszopiclone, zaleplon, or zolpidem.1,200

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 full 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 zaleplon.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 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 These behaviors can occur when these drugs are taken alone or when taken with alcohol or other CNS depressants.1,200 Discontinue zaleplon 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

CNS Depression and Next-day Impairment

Like other sedative-hypnotic drugs, zaleplon has CNS-depressant effects.1 Because of its rapid onset of action, zaleplon should only be taken immediately prior to going to bed or after the patient has gone to bed and has experienced difficulty falling asleep.1 Drowsiness and decreased levels of consciousness associated with zaleplon may increase the risk of falls, particularly in geriatric patients.1

Concomitant use of other CNS depressants (e.g., benzodiazepines, opiates, tricyclic antidepressants, alcohol) with zaleplon increases the risk of CNS depression.1 Because of the potential for additive effects, dosage adjustments of zaleplon and of concomitantly used CNS depressants may be necessary.1 The use of zaleplon with other sedative-hypnotic agents at bedtime or in the middle of the night is not recommended.1

The risk of next-day psychomotor impairment, including impaired driving, is increased if zaleplon is taken with less than a full night of sleep (7-8 hours) remaining; if a higher than recommended dose is taken; if administered concomitantly with other CNS depressants, alcohol, or drugs that increase the blood levels of zaleplon.1 Warn patients against driving and engaging in other activities requiring complete mental alertness if zaleplon is taken in these circumstances.1

Vehicle drivers and machine operators should be warned that, as with other sedative-hypnotic agents, there is a possible risk of adverse reactions (e.g., drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness, and impaired driving) the morning after therapy.1 In order to minimize this risk, a full night of sleep (7-8 hours) is recommended.1

Adequate Patient Evaluation

Since 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 The failure of insomnia to remit after 7-10 days of therapy may indicate the presence of an underlying psychiatric and/or medical condition requiring evaluation.1

Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder.1 Such findings have emerged during the course of treatment with sedative-hypnotic drugs, including zaleplon.1 Because some of the important adverse effects of zaleplon appear to be dose-related, it is important to use the lowest possible effective dose, especially in geriatric patients.1

Sensitivity Reactions

Rare cases of angioedema involving the tongue, glottis, or larynx have been reported in patients receiving their first or subsequent doses of sedatives-hypnotics, including zaleplon.1 Some patients have experienced additional symptoms such as dyspnea, closing of the throat, or nausea and vomiting that suggest anaphylaxis.1 Some of these patients have required medical treatment in an emergency department.1 If angioedema involves the tongue, glottis, or larynx, airway obstruction may occur, which could be fatal.1 Patients who develop angioedema following treatment with zaleplon should not be rechallenged with the drug.1

Some formulations of zaleplon contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.1 Although the incidence of tartrazine sensitivity is low, it frequently occurs in patients who are sensitive to aspirin.1

Abnormal Thinking and Behavioral Changes

Sedative-hypnotic agents are associated with numerous abnormal thought and behavioral processes (e.g., decreased inhibition, agitation, hallucinations, depersonalization, amnesia, depression/suicidal ideation); many are similar to manifestations of alcohol intoxication.1 Studies demonstrate short-term amnestic effects with zaleplon.1 Because of rapid clearance of the drug, amnestic effects peak at 1 hour after dosing, dissipate as early as 2 hours in some cases, and usually are gone within 3-4 hours; however, next-day memory impairment may occasionally occur and is dose dependent.1,3,8,12,13,17,20,23 As with other sedative-hypnotics, emergence of new psychiatric abnormalities during zaleplon therapy requires evaluation.1

Abuse Potential

Studies using relatively high zaleplon doses (2.5-7.5 times the recommended hypnotic dose) suggest abuse potential similar to benzodiazepine and related hypnotics; the drug should be used with caution in patients with a history of drug or alcohol dependence or abuse.1,4,10,12,20

Tolerance

No manifestations of tolerance for the therapeutic effects of zaleplon occurred during studies of 4 weeks' duration.1

Dependence

Physical dependence results in the manifestation of withdrawal symptoms (e.g., rebound insomnia, anxiety) upon rapid dose decrease or abrupt discontinuance of many sedative-hypnotics, including zaleplon.1 Rebound insomnia of 1 day's duration was noted in controlled and open-label studies, principally in patients receiving the 20-mg dose of zaleplon.1 Although premarketing studies did not reveal evidence of a withdrawal syndrome other than such mild rebound insomnia,1,2,12,14,15,18 studies to date do not provide a reliable estimate of the incidence of dependence with zaleplon; in addition, at least 2 cases of seizure (one with a seizure history) have been reported.1

Monitor patients closely during zaleplon discontinuance, as other sedative-hypnotics have manifested withdrawal symptoms such as seizures, vomiting, and abdominal cramps and experience with zaleplon to date is limited.1 Moreover, very short-acting hypnotics such as zaleplon may potentially demonstrate between-dose withdrawal symptoms, although no substantial clinical evidence of this phenomenon exists to date for zaleplon.1,2

Timing of Drug Doses

Ingesting zaleplon while still up and about could result in adverse CNS effects such as short-term memory impairment, hallucinations, dizziness, and impaired coordination.1 Therefore, administer immediately before retiring or after experiencing difficulty falling asleep.1

Geriatric or Debilitated Patients

Potential increased sensitivity to pharmacologic and adverse effects of hypnotic agents; use with caution and monitor such patients closely.1 To decrease the possibility of adverse effects, the recommended dosage of zaleplon in geriatric and/or debilitated patients is 5 mg.1

Concomitant Illness

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

In general, sedative-hypnotic agents have the potential to depress respiration.1 Although no reports of respiratory depression have been noted with recommended zaleplon doses in studies to date (including in patients with moderate obstructive sleep apnea or mild to moderate chronic obstructive pulmonary disease [COPD]),1,21 patients with impaired respiratory function due to preexisting illness should be monitored carefully during zaleplon therapy.1

Hepatic and Renal Disease

Reduce zaleplon dosage to 5 mg in patients with mild to moderate hepatic impairment.1 Use is not recommended in patients with severe hepatic impairment.1

No adjustment of zaleplon dosage is necessary in patients with mild to moderate renal impairment.1 Zaleplon has not been adequately studied in patients with severe renal impairment.1

Use in Patients with Depression

In primarily depressed patients treated with sedative-hypnotic agents, worsening of depression, including suicidal thoughts and actions (including completed suicides), have been reported.1 As with other sedative-hypnotic agents, zaleplon should be used with caution in patients with signs or symptoms of depression.1 Suicidal tendencies may be present in such patients and protective measures may be required.1 Intentional overdosage is more common in this patient population, and the least amount of drug that is feasible should be prescribed for the patient at any one time.1

Specific Populations

Pregnancy

There are no studies of zaleplon in pregnant women to date.1 The manufacturer does not recommend use in this population, and there is no established use of the drug in labor and delivery.1

Lactation

Zaleplon is distributed into milk.1,11 Since the effects of zaleplon on nursing infants are not known but even small amounts might be potentially important, the manufacturer does not recommend use in nursing women.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1,20

Geriatric Use

Patients ≥65 years of age may be more sensitive to pharmacologic and adverse effects of sedative-hypnotic agents;1 initial and maximum dose reduction recommended.1,19

Hepatic Impairment

Dosage reduction recommended for mild to moderate impairment; zaleplon use is not recommended in patients with severe impairment.1

Renal Impairment

Dosage adjustment is not necessary in mild to moderate renal impairment; zaleplon has not been adequately studied in patients with severe renal impairment.1

Common Adverse Effects

Adverse effects occurring in ≥5% of patients receiving zaleplon include headache, asthenia, dizziness, nausea, abdominal pain, and somnolence.1

Zaleplon is metabolized principally by aldehyde oxidase, and to a lesser extent by CYP3A4; all metabolites of the drug are inactive.1

Drugs Affecting Hepatic Microsomal Enzymes

Cytochrome P-450 Isoenzyme 3A4 Inducers

Potential pharmacokinetic interaction with CYP3A4 inducers such as rifampin, phenytoin, carbamazepine, and phenobarbital: may result in decreased efficacy of zaleplon.1 Multiple-dose administration of rifampin (600 mg every 24 hours for 14 days) reduced zaleplon peak concentrations and AUC by approximately 80%.1 Consider an alternative sedative-hypnotic agent that is not a CYP3A4 substrate in patients receiving CYP3A4 inducers.1

Cytochrome P-450 Isoenzyme 3A4 Inhibitors

Clinically important pharmacokinetic interaction is unlikely; routine adjustments of zaleplon dosage are not considered necessary when the drug is used concomitantly with CYP3A4 inhibitors.1 Concomitant administration of single, oral doses of zaleplon (10 mg) and erythromycin (800 mg), a strong, selective CYP3A4 inhibitor, resulted in increases in zaleplon peak plasma concentration and AUC of 34 and 20%, respectively.1 The effects of concomitant use of multiple doses of erythromycin on zaleplon pharmacokinetics are unknown.1 Other strong, selective CYP3A4 inhibitors (e.g., ketoconazole) also are expected to increase zaleplon exposure.1

Protein-bound Drugs

Zaleplon is not highly bound to plasma proteins; therefore, the disposition of zaleplon is not expected to be sensitive to alterations in protein binding.1 In addition, administration of zaleplon in patients receiving a highly protein-bound drug is not expected to cause a transient increase in free (unbound) concentration of the highly protein-bound drug.1

CNS Depressants

Potential pharmacodynamic interaction with other CNS depressants such as alcohol, imipramine, thioridazine, and diphenhydramine; anesthetics; anticonvulsants; antihistamines; sedatives and hypnotics; and opiates: may result in additive CNS effects.1,22,200 Concomitant administration of single doses of zaleplon 20 mg and imipramine 75 mg resulted in additive effects of decreased alertness and impaired psychomotor performance for 2-4 hours after administration; no alterations in the pharmacokinetics of either drug were observed.1 Concomitant administration of single doses of zaleplon 20 mg and thioridazine 50 mg resulted in additive effects of decreased alertness and impaired psychomotor performance for 2-4 hours after administration; no alterations in the pharmacokinetics of either drug were observed.1

Concomitant use of sedative and hypnotic drugs used to treat insomnia should be avoided in patients receiving zaleplon.1,200

Dosage adjustment of zaleplon and/or other CNS depressants may be necessary during concomitant use.1

Alcohol

Potential pharmacodynamic interaction with alcohol: additive CNS effects.1,22,200 Administration of zaleplon 10 mg potentiated the CNS-impairing effects of ethanol 0.75 g/kg on balance testing and reaction time for 1 hour after ethanol administration and on the digit symbol substitution test (DSST), symbol copying test, and the variability component of the divided attention test for 2.5 hours after ethanol administration.1 Zaleplon did not affect the pharmacokinetics of ethanol.1 Alcohol should be avoided during zaleplon therapy.1,200

Cimetidine

Potential pharmacokinetic (CYP3A4 and aldehyde oxidase inhibition) interaction; initial zaleplon dose reduction to 5 mg recommended.1,22

Diphenhydramine

Pharmacokinetic (aldehyde oxidase inhibition) interaction unlikely; possible additive pharmacodynamic (CNS depressant) effect.1,22

Digoxin

Administration of zaleplon (10 mg) did not affect the pharmacokinetic or pharmacodynamic profile of digoxin (375 mcg once daily for 8 days).1,22

Ibuprofen

Pharmacokinetic interaction unlikely.1,22

Paroxetine

Concomitant administration of a single 20-mg dose of zaleplon and paroxetine 20 mg daily for 7 days did not result in any pharmacodynamic interaction related to psychomotor performance.1 In addition, the pharmacokinetics of zaleplon were not affected by paroxetine (a CYP2D6 inhibitor).1

Promethazine

Pharmacokinetic interaction unlikely; possible additive CNS effects.1 Concomitant administration of single doses of zaleplon 10 mg and promethazine 25 mg resulted in a 15% decrease in zaleplon peak plasma concentrations and no change in zaleplon AUC; however, the possible pharmacodynamic interaction between zaleplon and promethazine has not been evaluated.1 The manufacturer recommends using zaleplon and promethazine concomitantly with caution.1

Venlafaxine

Pharmacokinetic interaction unlikely.1 Concomitant administration of multiple doses of extended-release venlafaxine 150 mg and a single 10-mg dose of zaleplon did not result in a pharmacodynamic interaction and did not alter pharmacokinetics of either drug.1

Warfarin

Pharmacokinetic or pharmacodynamic (prothrombin time) interactions unlikely.1,22

Description

Zaleplon, a pyrazolopyrimidine derivative, is a sedative and hypnotic agent structurally unrelated to the benzodiazepines and other sedative-hypnotic agents.1,2,3,4,12,13,18 Pharmacologically and pharmacokinetically, zaleplon is similar to zolpidem; both are hypnotic agents with short half-lives, and both have been shown to interact with the CNS γ-aminobutyric acid (GABA_A)-receptor-chloride ionophore complex at benzodiazepine (BZ) omega-1 (BZ₁, ω₁) receptors.1,2,3,5,6,7,12,13,18 In contrast, some benzodiazepines nonselectively activate central BZ₁ (ω₁) and BZ₂ (ω₂) receptors as well as peripheral BZ₃ (ω₃) receptors, resulting in nonspecific pharmacologic actions.3

Zaleplon is extensively metabolized, principally by aldehyde oxidase, and to a lesser extent by the cytochrome P-450 (CYP) isoenzyme 3A4.1,9 Zaleplon generally appears to be absorbed and eliminated more rapidly than zolpidem.8,13,20

Advice to Patients

• Provide patients with a copy of the manufacturer's medication guide.1
• Advise patients to administer the drug immediately before retiring, or after attempting to fall asleep, and only when able to get a full night's sleep (7-8 hours) before it is necessary to be active again.1,17,200
• Advise patients to avoid taking zaleplon with or immediately after a meal.1
• Instruct patients to take zaleplon only as prescribed; do not increase the dose 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
• 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 zaleplon 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
• Advise patients to exercise caution when operating machinery or performing hazardous tasks while using zaleplon and to avoid these activities until they feel fully awake.1,12,17 Inform patients that the risk of next-day psychomotor impairment, including impaired driving, is increased if zaleplon is taken with less than a full night of sleep (7-8 hours) remaining; if a higher than recommended dose is taken; if coadministered with other CNS depressants or alcohol; or if coadministered with other drugs that increase the blood levels of zaleplon; warn patients against driving and other activities requiring complete mental alertness if the drug is taken in these circumstances.1
• Warn vehicle drivers and machine operators of the possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness, and impaired driving the morning after therapy; in order to minimize this risk a full night of sleep (7-8 hours) is recommended.1
• Advise patients to avoid alcohol1,22,200 and concurrent use of other sedative-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
• Advise patients that drowsiness and decreased consciousness may increase the risk of falls in some patients.1
• Potential risk of severe hypersensitivity reactions; advise patients to immediately seek medical care if manifestations (e.g., angioedema, dyspnea, nausea, vomiting) of such reactions occur.1
• Instruct patients to identify and report to clinicians any potential adverse effects, such as memory impairment, anxiety, or abnormal thinking or behavioral changes.1
• Advise patient of possible rebound insomnia and withdrawal symptoms (e.g., unpleasant feelings, stomach and muscle cramps, vomiting, sweating, shakiness; seizures) for 1 or 2 nights after discontinuance.1
• Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., psychiatric disorders including depression or suicidality, history of drug or alcohol abuse or addiction, kidney or liver disease, lung disease or breathing difficulty).1,22
• Advise women to inform clinicians 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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