Introduction
Zaleplon is a non-benzodiazepine hypnotic agent approved for the short-term treatment of insomnia. Marketed under the brand name Sonata, it belongs to the pyrazolopyrimidine class and is classified as a Schedule IV controlled substance due to its potential for dependence.
Mechanism of Action
Zaleplon exerts its therapeutic effects through selective agonism at the benzodiazepine receptor site on the GABA-A receptor complex. This binding enhances GABAergic neurotransmission by increasing the frequency of chloride channel opening, resulting in neuronal hyperpolarization and CNS depression. Unlike benzodiazepines, zaleplon demonstrates relative selectivity for the ω1 receptor subtype, which is associated with sedative effects rather than anxiolytic, muscle relaxant, or anticonvulsant properties.
Indications
- Short-term treatment of insomnia characterized by difficulty with sleep initiation
- Not indicated for sleep maintenance insomnia due to its ultrashort half-life
Dosage and Administration
Standard adult dose: 10 mg orally once daily at bedtime Maximum dose: 20 mg daily Special populations:- Elderly/debilitated patients: 5 mg initially
- Hepatic impairment: 5 mg initially
- Renal impairment: No dosage adjustment typically needed
- Take immediately before bedtime or after going to bed when difficulty falling asleep is experienced
- Must ensure 7-8 hours dedicated to sleep after administration
- Should not be taken with or immediately after a high-fat meal
Pharmacokinetics
Absorption: Rapidly absorbed with peak concentrations reached in approximately 1 hour Bioavailability: ~30% due to significant first-pass metabolism Distribution: Volume of distribution: 1.4 L/kg; 60% protein bound Metabolism: Extensive hepatic metabolism via aldehyde oxidase to 5-oxo-zaleplon and via CYP3A4 to desethylzaleplon Elimination: Half-life: approximately 1 hour; excreted primarily in urine (71%) with <1% as unchanged drugContraindications
- Hypersensitivity to zaleplon or any component of the formulation
- Severe hepatic impairment
- Concurrent use with potent CYP3A4 inhibitors
- History of complex sleep behaviors after taking zaleplon
Warnings and Precautions
- Complex sleep behaviors: Reports of sleep-walking, sleep-driving, and other complex behaviors without recall
- CNS depression: Additive effects with other CNS depressants; impaired alertness the next day
- Tolerance/dependence: Potential for abuse, dependence, and withdrawal symptoms
- Depression: May worsen depression; monitor for suicidal ideation
- Respiratory depression: Use with caution in patients with respiratory compromise
- Pregnancy: Category C - potential fetal risk
Drug Interactions
Major interactions:- CNS depressants: Opioids, benzodiazepines, alcohol - additive sedation
- CYP3A4 inhibitors: Ketoconazole, clarithromycin - increased zaleplon levels
- CYP3A4 inducers: Rifampin, carbamazepine - decreased efficacy
- Selective serotonin reuptake inhibitors
- Tricyclic antidepressants
- Antihistamines
Adverse Effects
Common (≥5%):- Headache (28-42%)
- Dizziness (7-9%)
- Somnolence (5-6%)
- Nausea (4-5%)
- Anaphylaxis
- Complex sleep behaviors
- Memory impairment
- Depression/suicidal ideation
- Withdrawal seizures
Monitoring Parameters
- Sleep pattern improvement and daytime alertness
- Signs of tolerance or dependence
- Cognitive and psychomotor function
- Mood changes, especially depression
- Adverse effects, particularly complex sleep behaviors
- Renal and hepatic function in long-term use
Patient Education
- Take immediately before bedtime when ready to sleep
- Ensure 7-8 hours of uninterrupted sleep after dosing
- Avoid alcohol and other sedating medications
- Report any unusual sleep behaviors or memory problems
- Do not increase dose without medical supervision
- Be aware of potential next-day impairment
- Use only for short-term treatment (2-3 weeks typically)
- Taper gradually if discontinuing after prolonged use
References
1. FDA prescribing information: Sonata (zaleplon) capsules 2. Drover DR. Clinical pharmacokinetics and pharmacodynamics of zaleplon. Clin Pharmacokinet. 2004;43(4):227-38. 3. Walsh JK, et al. Efficacy and tolerability of zaleplon in the treatment of insomnia. Clin Drug Investig. 2000;20(2):143-53. 4. American Academy of Sleep Medicine. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults. J Clin Sleep Med. 2017;13(2):307-349. 5. Schutte-Rodin S, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504. 6. Micromedex Solutions: Zaleplon Drug Information