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
Brands: Sonata

Medically reviewed by Drugs.com on Oct 11, 2021. 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.

Zaleplon Dosage and Administration

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. (See Food under Pharmacokinetics.)

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

Use only when able to get ≥4 hours of sleep; amnesic episodes may result with less (e.g., overnight flight of <4 hours’ duration) 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.

Generally, limit use to 7–10 days; reevaluate patient if plan to use >2–3 weeks.

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 may be sufficient; doses >10 mg not recommended.

Debilitated or Low-weight Patients

In debilitated patients or low-weight patients <65 years of age, 5 mg may be sufficient; doses >10 mg not recommended.

Patients Receiving Cimetidine

In patients receiving cimetidine concomitantly, initial dose of 5 mg recommended. (See Specific Drugs under Interactions.)

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. (See Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors under Cautions.)

Warnings/Precautions

Warnings

Risk of Serious Injury and Death Resulting From Complex Sleep Behaviors

Complex sleep behaviors, in which patients engage in activities while they are not fully awake, sometimes resulting in serious injuries and/or death reported rarely with eszopiclone, zaleplon, and zolpidem. 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). These behaviors can occur when these drugs are taken alone or with alcohol or other CNS depressants. (See Specific Drugs under Interactions.)

FDA states that serious injuries and fatalities resulting 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 eszopiclone, zaleplon, and zolpidem. 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 have been reported.

Warn patients about risk of complex sleep behaviors. Discontinue zaleplon if a complex sleep behavior occurs. (See Contraindications under Cautions and also see Advice to Patients.)

Other Warnings and Precautions

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.

Adverse Psychiatric Events

Abnormal thinking and behavioral changes (e.g. aggressiveness, uncharacteristic extroversion, bizarre behavior, agitation, hallucinations, depersonalization, amnesia) may occur unpredictably. Immediately evaluate any new behavioral sign or symptom.

Withdrawal Effects

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.

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.

CNS Effects

Rapid onset of CNS effects (short-term memory impairment, hallucinations, impaired coordination, dizziness, lightheadedness); administer only immediately before going to bed or after unsuccessfully attempting to sleep.

Performance of activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) may be impaired the day after ingestion.

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression. (See Specific Drugs under Interactions.)

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema in patients receiving their first or subsequent doses of sedatives-hypnotics, including zaleplon. In patients who develop angioedema following treatment with zaleplon, do not rechallenge patient with the drug.

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

Respiratory Effects

Possible depressed respiration with sedative-hypnotics. No respiratory depressant effects reported at hypnotic doses of zaleplon in healthy individuals or in patients with mild to moderate COPD or moderate obstructive sleep apnea.

Caution is advised in patients with impaired respiratory function.

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 in studies to date (including in patients with obstructive sleep apnea or COPD), carefully monitor patients with impaired respiratory function during therapy.

Use in Patients with Depression

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. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Reduce dosage for mild to moderate hepatic impairment. Use not recommended in patients with severe hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

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. (See Debilitated or Low-weight Patients under Dosage and Administration.)

Common Adverse Effects

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%. (See Hepatic Impairment under Dosage and Administration.)

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

• Importance of advising patients to read the manufacturer's medication guide prior to initiating zaleplon therapy and each time the prescription is refilled.

• Importance of administering immediately before retiring, or after attempting to fall asleep, and only when able to get ≥4 hours of sleep before it is necessary to be active again.

• Importance of avoiding administration with or immediately after a high-fat meal.

• Importance of taking only as prescribed; do not increase the dose or duration of therapy unless otherwise instructed by a clinician.

• Risk of serious injury and/or death resulting from complex sleep behaviors. Importance of discontinuing zaleplon and notifying a clinician immediately if an episode of complex sleep behavior occurs during therapy, even if it did not result in a serious injury.

• Necessity of exercising caution when operating machinery or performing hazardous tasks while using zaleplon; importance of avoidance of alcohol and 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.

• Importance of identifying and reporting to clinicians any potential adverse effects, such as memory impairment, dependence/withdrawal symptoms after multiple dosing, behavioral abnormalities, or tolerance potential.

• Advise patient of possible rebound insomnia for 1 or 2 nights after discontinuance.

• Importance of informing 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).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

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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