Use with caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of drug dependence. Abrupt discontinuance may lead to withdrawal symptoms. May impair physical and mental capabilities. Patients must be cautioned about performing tasks which require mental alertness (operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive medications. Effects with other sedative drugs or ethanol may be potentiated.

Use with caution in the elderly, those with compromised respiratory function, or renal and hepatic impairment. Because of the rapid onset of action, zaleplon should be administered immediately prior to bedtime or after the patient has gone to bed and is having difficulty falling asleep. Capsules contain tartrazine (FDC yellow #5); avoid in patients with sensitivity (caution in patients with asthma).

1% to 10%:

Cardiovascular: Peripheral edema, chest pain

Central nervous system: Amnesia, anxiety, depersonalization, dizziness, hallucinations, hypesthesia, somnolence, vertigo, malaise, depression, lightheadedness, impaired coordination, fever, migraine

Dermatologic: Photosensitivity reaction, rash, pruritus

Gastrointestinal: Abdominal pain, anorexia, colitis, dyspepsia, nausea, constipation, xerostomia

Genitourinary: Dysmenorrhea

Neuromuscular & skeletal: Paresthesia, tremor, myalgia, weakness, back pain, arthralgia

Ocular: Abnormal vision, eye pain

Otic: Hyperacusis

Miscellaneous: Parosmia

<1% (Limited to important or life-threatening): Alopecia, angina, ataxia, bundle branch block, circumoral paresthesia, dysarthria, dystonia, eosinophilia, facial paralysis, glaucoma, intestinal obstruction, pericardial effusion, ptosis, pulmonary embolus, syncope, urinary retention, ventricular tachycardia

Antipsychotics: Zaleplon potentiates the CNS effects of thioridazine (and potentially other antipsychotics)

Cimetidine: May increase zaleplon levels by decreasing its metabolism; cimetidine inhibits both aldehyde oxidase and CYP3A4 leading to an 85% increase in Cmax and AUC of zaleplon; use 5 mg zaleplon as starting dose in patients receiving cimetidine

CNS depressants: Sedative effects may be additive with psychotropics; monitor for increased effect; includes anticonvulsants, antipsychotics, barbiturates, benzodiazepines, narcotic analgesics, ethanol, and other sedative agents

Tricyclic antidepressants: Zaleplon potentiates the CNS effects of imipramine (and potentially other TCAs)

Ethanol: Avoid ethanol (may increase CNS depression).

Food: High fat meal prolonged absorption; delayed tmax by 2 hours, and reduced Cmax by 35%.

Herb/Nutraceutical: St John's wort may decrease zaleplon levels. Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Onset of action: Rapid

Peak effect: ~1 hour

Duration: 6-8 hours

Absorption: Rapid and almost complete

Distribution: Vd: 1.4 L/kg

Protein binding: 60% ± 15%

Metabolism: Extensive, primarily via aldehyde oxidase to form 5-oxo-zaleplon and to a lesser extent by CYP3A4 to desethylzaleplon; all metabolites are pharmacologically inactive

Bioavailability: 30%

Half-life elimination: 1 hour

Time to peak, serum: 1 hour

Excretion: Urine (primarily metabolites, <1% as unchanged drug)

Clearance: Plasma: Oral: 3 L/hour/kg

Adults: 10 mg at bedtime (range: 5-20 mg); has been used for up to 5 weeks of treatment in controlled trial setting

Elderly: 5 mg at bedtime

Dosage adjustment in renal impairment: No adjustment for mild to moderate renal impairment; use in severe renal impairment has not been adequately studied

Dosage adjustment in hepatic impairment: Mild to moderate impairment: 5 mg; not recommended for use in patients with severe hepatic impairment