Section 10 · Monograph

Zaleplon

Reviewed Nov 2026FDA label

SonataNonbenzodiazepine hypnotic (Z-drug)

Black Box Warning

COMPLEX SLEEP BEHAVIORS: Complex sleep behaviors, including sleepwalking, sleep-driving, and engaging in other activities while not fully awake, may occur following use of zaleplon. Some of these events have resulted in serious injuries, including death.
These behaviors appear more likely with concomitant alcohol or other CNS depressants and at doses exceeding the maximum recommended dose, but have occurred with zaleplon alone at recommended doses.
Discontinue immediately if a patient experiences an episode of complex sleep behavior.
Zaleplon is contraindicated in patients who have experienced a complex sleep behavior after taking zaleplon.

Short-term treatment of insomnia in adults, to decrease time to sleep onset (studied for up to 30 days); has not been shown to increase total sleep time or decrease the number of nighttime awakenings.FDA-labeled

As-needed dosing for middle-of-the-night awakenings (leveraging its ultra-short half-life), provided at least 4 hours of planned sleep time remain.Off-label
Short-term/transient insomnia (e.g., jet lag).Off-label

Zaleplon is a nonbenzodiazepine hypnotic of the pyrazolopyrimidine chemical class, structurally distinct from benzodiazepines, eszopiclone, and zolpidem.
Interacts with the GABA-A/benzodiazepine receptor-chloride ionophore complex, with relatively selective binding to the omega-1 (BZ1) receptor subtype.
Lower affinity for omega-2 receptor subtypes compared with benzodiazepines, consistent with its more selective hypnotic profile.
Rapid onset and ultra-short elimination half-life (~1 hour) are central to its intended use and dosing restrictions relative to remaining sleep time.

Adults: 10 mg orally immediately before bedtime, or after the patient has gone to bed and experienced difficulty falling asleep, provided at least 4 hours remain before planned awakening. Effective range 5-20 mg; doses above 10 mg generally not recommended due to increased next-day psychomotor impairment and amnesia.
Low-weight, elderly, or debilitated patients: start at 5 mg; doses above 10 mg not recommended.
Concomitant cimetidine: reduce starting dose to 5 mg.
Avoid administration with or immediately after a high-fat/heavy meal.
Intended for short-term use; reassess need for continued therapy regularly.

Renal impairment: no adjustment needed for mild-to-moderate impairment; severe impairment not adequately studied.

Mild-to-moderate hepatic impairment: 5 mg starting dose; not recommended in severe hepatic impairment.

CNS depressants (alcohol, opioids, benzodiazepines, tricyclic antidepressants, antipsychotics): additive sedation and psychomotor impairment.
Cimetidine: increases zaleplon Cmax and AUC by ~85% — reduce zaleplon starting dose to 5 mg.
CYP3A4 inducers (rifampin): decrease zaleplon exposure by ~80%, potentially reducing efficacy.
CYP3A4 inhibitors (erythromycin): increase zaleplon Cmax by ~34% — modest effect, use with caution.
Primarily metabolized by aldehyde oxidase (non-CYP pathway), with minor CYP3A4 contribution.
No clinically significant interaction demonstrated with warfarin, digoxin, imipramine, ibuprofen, or diphenhydramine.

Headache (up to ~42% at 20 mg dose), dizziness, nausea, somnolence — most common, dose-related.
Amnesia/anterograde memory impairment, particularly at the 20 mg dose.
Complex sleep behaviors — boxed warning.
Next-day psychomotor impairment, especially if taken with less than 4 hours of sleep opportunity remaining.
Abnormal thinking and behavioral changes: aggression, agitation, hallucinations, depersonalization, decreased inhibition.
Rebound insomnia, primarily at the 20 mg dose.
Rare angioedema of the tongue, glottis, or larynx — potential airway obstruction.
Worsening depression, including emergent suicidal thoughts and actions.
Physical/psychological dependence potential (Schedule IV).

Confirm patient has at least 4 hours of planned sleep time remaining before dosing.
Reassess if insomnia does not remit within 7-10 days.
Monitor for complex sleep behaviors, particularly with dose increases or concomitant CNS depressant/alcohol use.
Monitor mood/depression status and for emergent suicidal ideation.
Monitor for signs of tolerance, misuse, or withdrawal with continued use.
Assess hepatic function in patients with hepatic impairment; avoid in severe impairment.
Screen for concomitant CNS depressant or alcohol use at each visit.

Pregnancy: Zaleplon is not recommended for use during pregnancy; human data are limited. Animal studies showed reduced offspring growth at high maternal doses without clear evidence of teratogenicity.
Lactation: It is recommended that nursing mothers not take zaleplon. A small amount is excreted into breast milk, with potential for infant exposure and sedation.