Brand name: Sonata
Drug class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA class: CN309
Chemical name: N-[3-(3-cyanopyrazolo[1,5-α]pyrimidin-7-yl)phenyl]-N-ethyl-acetamide
Molecular formula: C₁₇H₁₅N₅O
CAS number: 151319-34-5

Medically reviewed by Drugs.com on Apr 27, 2023. Written by ASHP.

Introduction

Pyrazolopyrimidine-derivative sedative and hypnotic; structurally unrelated to benzodiazepines and other sedatives and hypnotics.

Uses for Zaleplon

Insomnia

Short-term management of insomnia.

Decreases sleep latency with repeated use for periods up to 30 days in duration.

Most useful for sleep initiation disorders; does not substantially increase total sleep time or decrease the number of awakenings.

Psychological and behavioral interventions are recommended as initial treatment for insomnia according to the American Academy of Sleep Medicine (AASM) and American College of Physicians (ACP) guidelines. When pharmacologic therapy is indicated, choice of agent should be directed by symptoms, treatment goals, past treatment response, patient preference, cost and availability, comorbid conditions/contraindications, concomitant drug therapy/interactions, and potential adverse effects. Zaleplon is among several agents recommended for treatment of sleep onset insomnia. The lowest effective dosage and short-term (4–5 weeks) treatment are recommended.

Zaleplon Dosage and Administration

General

Pretreatment Screening

• Screen patients for diseases or conditions that may affect drug metabolism or hemodynamic responses; use zaleplon with caution in such patients.

• 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.

• Screen patients for a history of addiction to, or abuse of, drugs or alcohol.

Patient Monitoring

• Monitor for abnormal thinking and behavioral changes; carefully and immediately evaluate any new and concerning behavioral sign or symptom.

• Monitor geriatric and/or debilitated patients closely for adverse effects.

• Monitor patients with a history of addiction to, or abuse of, drugs or alcohol closely for zaleplon habituation and dependence.

Administration

Oral Administration

Administer orally, generally without regard to meals.

Avoid administration with a high-fat or heavy meal; may decrease rate of absorption and effect on sleep latency.

Administer immediately before retiring (when ready to sleep) or after retiring when experiencing difficulty falling asleep.

Use only when able to get a full night of sleep.

Dosage

Adults

Insomnia

Oral

Individualize dosage. Use the lowest effective dosage in all patient populations.

Adults <65 years of age: 10 mg. Although risk of certain adverse effects appears to be dose dependent, 20-mg doses have been adequately tolerated; may consider if unresponsive to a trial of lower dosage.

Prescribing Limits

Adults

Insomnia

Doses >20 mg not adequately studied; not recommended by manufacturer.

Special Populations

Hepatic Impairment

In patients with mild to moderate hepatic impairment, 5 mg. Not recommended in patients with severe hepatic impairment.

Renal Impairment

No dosage adjustment necessary in patients with mild to moderate renal impairment. Not adequately studied in patients with severe renal impairment.

Geriatric Patients

In adults ≥65 years of age, 5 mg; doses >10 mg not recommended.

Debilitated Patients

In debilitated patients, 5 mg; doses >10 mg not recommended.

Low-weight Patients

In low-weight patients <65 years of age, 5 mg may be sufficient.

Japanese Patients

Japanese adults demonstrated pharmacokinetic parameter differences; may be explained by differences in body weight or hepatic enzyme activity.

Patients Receiving Cimetidine

In patients receiving cimetidine concomitantly, initial dose of 5 mg recommended.

Cautions for Zaleplon

Contraindications

• Hypersensitivity to zaleplon or any ingredient in the formulation.

• History of a complex sleep behavior while taking eszopiclone, zaleplon, or zolpidem.

Warnings/Precautions

Warnings

Complex Sleep Behaviors

Complex sleep behaviors in which patients engage in activities while they are not fully awake reported; may result in serious injuries and/or death. (See Boxed Warning.) Such behaviors may include 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).

Falls with serious injuries reported.

Can occur when sedative-hypnotic agents are taken alone or with alcohol or other CNS depressants.

Discontinue zaleplon immediately if complex sleep behavior occurs.

Other Warnings and Precautions

CNS Depression and Next-day Impairment

CNS depressant with rapid onset of action; administer immediately prior to going to bed or after patient has gone to bed and has experienced difficulty falling asleep.

Concomitant use of other CNS depressants (e.g., benzodiazepines, opiates, tricyclic antidepressants, alcohol) increases risk of CNS depression. Dosage adjustments of zaleplon and of concomitantly used CNS depressants may be necessary. Concomitant use of other sedative-hypnotic agents at bedtime or in the middle of the night not recommended.

Risk of next-day psychomotor impairment, including impaired driving, 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; and if administered concomitantly with other CNS depressants, alcohol, or drugs that increase the blood levels of zaleplon. Warn patients against driving and engaging in other activities requiring complete mental alertness if drug is taken in these circumstances.

Warn vehicle drivers and machine operators of 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. In order to minimize this risk, a full night of sleep (7–8 hours) is recommended.

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

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric and/or medical condition.

Some important adverse effects of zaleplon appear dose-related; use lowest possible effective dose, especially in geriatric patients.

Sensitivity Reactions

Angioedema involving the tongue, glottis, or larynx reported following initial or subsequent doses of sedative and hypnotic drugs, including zaleplon; may result in airway obstruction and death. Anaphylaxis also reported.

Do not rechallenge with the drug if angioedema occurs.

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

Abnormal Thinking and Behavioral Changes

Abnormal thinking and behavioral changes (e.g. decreased inhibition, agitation, hallucinations, depersonalization, amnesia, depression/suicidal ideation); many are similar to manifestations of alcohol intoxication.

Immediately evaluate any new behavioral sign or symptom.

Abuse Potential

Abuse potential of high doses (2.5–7.5 times recommended hypnotic dose) similar to that of benzodiazepines and related hypnotics.

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.

Tolerance

No tolerance for the therapeutic effects of zaleplon seen during studies of 4 weeks' duration.

Dependence

Rapid dosage reduction or abrupt discontinuance of sedatives or hypnotics has resulted in signs or symptoms of withdrawal.

Rebound insomnia (1 day in duration) observed, principally in patients receiving 20-mg dose. At least 2 cases of seizure (1 with seizure history) reported.

Timing of Drug Doses

Administer zaleplon immediately before retiring or after experiencing difficulty falling asleep. Ingesting while still awake could results in adverse CNS effects.

Concomitant Illness

Limited experience in patients with concomitant illness. Use with caution in patients with diseases or conditions affecting metabolism or hemodynamic response.

Sedative-hypnotic agents generally can depress respiration. Although respiratory depression not observed with recommended zaleplon dosages to date (including in patients with moderate obstructive sleep apnea or mild to moderate COPD), carefully monitor patients with impaired respiratory function during therapy.

Use in Patients with Depression

Worsening of depression, including suicidal thoughts and actions (including completed suicides), reported in primarily depressed patients treated with sedative-hypnotic agents. As with other sedative-hypnotic agents, use with caution in patients with signs or symptoms of depression.

Potential for suicidal tendencies; protective measures may be required. Intentional overdosage more frequent in such patients.

Prescribe drug in the smallest feasible quantity.

Specific Populations

Pregnancy

No studies to date in pregnant women. The manufacturer does not recommend use in this population, and there is no established use in labor and delivery.

Lactation

Distributed into milk. Use not recommended.

Pediatric Use

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

Geriatric Use

Possibility exists of greater sensitivity to pharmacologic and adverse effects of sedatives and hypnotics in patients ≥65 years of age; reduce initial and maximum dose.

Hepatic Impairment

Reduce dosage for mild to moderate hepatic impairment. Use not recommended in patients with severe hepatic impairment.

Renal Impairment

Dosage adjustment not necessary in patients with mild to moderate renal impairment. Has not been adequately studied in patients with severe renal impairment.

Debilitated Patients

Potential increased sensitivity to sedatives and hypnotics or impaired motor performance after repeated exposure. Reduce dosage and monitor closely.

Common Adverse Effects

Adverse effects (≥5%): Headache, asthenia, dizziness, nausea, abdominal pain, somnolence.

Interactions for Zaleplon

Metabolized principally by aldehyde oxidase, and to a lesser extent by CYP3A4; metabolites are inactive.

Drugs Affecting Hepatic Microsomal Enzymes

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma zaleplon concentrations); may result in decreased efficacy of zaleplon.

Potent, selective inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma zaleplon concentrations); routine dosage adjustment not considered necessary.

Protein-bound Drugs

Pharmacokinetic interaction unlikely.

Specific Drugs

Zaleplon Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed after oral administration, with peak plasma concentrations attained in approximately 1 hour. Absolute oral bioavailability is about 30%.

Food

High-fat or heavy meal decreases peak plasma concentration by approximately 35% and prolongs time to peak plasma concentration by approximately 2 hours; AUC and elimination half-life not substantially affected. Effect on sleep onset may be decreased.

Special Populations

In Japanese patients, peak plasma concentrations and AUC were increased 37 and 64%, respectively; may be attributed to differences in body weight or enzyme activity resulting from differences in diet, environment, or other factors.

Distribution

Extent

Extensively distributed into extravascular tissues.

Plasma Protein Binding

Approximately 60% (range: 45–75%).

Elimination

Metabolism

Extensively metabolized, principally by aldehyde oxidase and to a lesser extent by CYP3A4. All metabolites are inactive.

Elimination Route

Principally in urine (70%) as metabolites within 48 hours; also excreted in feces (17%), mainly as 5-oxo-zaleplon.

Half-life

About 1 hour.

Special Populations

In patients with cirrhosis, oral clearance is decreased by 70–87%.

Renal excretion of unchanged drug accounts for <1% of an administered dose; pharmacokinetics are not altered in patients with renal impairment. Not studied in severe renal impairment.

Pharmacokinetics do not appear to be affected by age (including ≥75 years) or sex.

Stability

Storage

Oral

Capsules

Tight, light-resistant containers at 20–25°C.

Actions

• Interacts with the CNS GABA_A-receptor-chloride ionophore complex at benzodiazepine (BZ) omega-1 (BZ₁, ο₁) receptors.

• Pharmacologically and pharmacokinetically similar to zolpidem.

Advice to Patients

• Provide patients with a copy of the manufacturer's medication guide.

• 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.

• Advise patients to avoid taking zaleplon with or immediately after a meal.

• Instruct patients to take zaleplon only as prescribed; do not increase the dose or duration of therapy unless otherwise instructed by a clinician.

• Advise patients to contact their clinician if their insomnia worsens or does not improve within 7–10 days of treatment.

• 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). 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.

• 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. 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.

• 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.

• Advise patients to avoid alcohol 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.

• Advise patients that drowsiness and decreased consciousness may increase the risk of falls in some patients.

• 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.

• Instruct patients to identify and report to clinicians any potential adverse effects, such as memory impairment, anxiety, or abnormal thinking or behavioral changes.

• 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.

• 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).

• Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information. (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.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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