What is the recommended dosing for Sonata (zaleplon) in a patient with insomnia, considering factors such as age, medical history, and potential for drug interactions?

Sonata (Zaleplon) Dosing for Insomnia

The recommended dose of zaleplon is 10 mg taken immediately before bedtime for adults with sleep onset insomnia, with dose reduction to 5 mg for elderly patients, those with hepatic impairment, or those taking cimetidine. 1, 2

Standard Adult Dosing

• Start with 10 mg at bedtime for most non-elderly adults with sleep onset insomnia 1, 2
• The 10 mg dose reduces sleep latency by approximately 10-20 minutes (15-30% improvement) compared to placebo 2
• The 5 mg dose is less consistently effective and did not demonstrate clinically significant improvement in objective sleep studies 1, 2
• The 20 mg dose shows greater efficacy but exceeds FDA-recommended dosing and carries increased risk of next-day amnesia and psychomotor impairment 1, 2

Elderly Patients (≥65 Years)

• Use 5 mg at bedtime as the starting and usual dose 1, 2
• The 10 mg dose may be considered if 5 mg is insufficient, as both doses were superior to placebo in elderly patients with similar effect sizes to younger adults 2
• Pharmacokinetics are not significantly different in elderly patients compared to younger adults, but lower dosing reduces risk of falls and cognitive impairment 2

Hepatic Impairment

• Reduce dose to 5 mg in patients with mild to moderate hepatic impairment 2
• Zaleplon clearance is reduced by 70% in compensated cirrhosis and 87% in decompensated cirrhosis, leading to 4-7 fold increases in drug exposure 2
• Zaleplon is not recommended in patients with severe hepatic impairment 2

Renal Impairment

• No dose adjustment necessary for mild to moderate renal impairment, as renal excretion accounts for <1% of elimination 2
• Zaleplon has not been adequately studied in severe renal impairment 2

Administration Guidelines

• Take on an empty stomach immediately before bedtime 2
• High-fat/heavy meals delay absorption by approximately 2 hours and reduce peak concentration by 35%, which may reduce effectiveness for sleep onset 2
• Do not take with or immediately after meals 2
• Zaleplon's ultra-short half-life (approximately 1 hour) allows for middle-of-the-night dosing if at least 4 hours remain before planned awakening, without next-day residual effects 3, 4, 5

Drug Interactions Requiring Dose Adjustment

• Reduce to 5 mg when co-administered with cimetidine, which increases zaleplon exposure by inhibiting aldehyde oxidase metabolism 2
• CYP3A4 inhibitors may also increase zaleplon levels, though specific dose adjustments are not established 2

Clinical Efficacy Considerations

• Zaleplon is effective only for sleep onset insomnia, not sleep maintenance 1, 3
• Sleep duration and number of awakenings are not significantly improved with 5 or 10 mg doses 1, 2, 4
• Effects on sleep latency persist for up to 35 nights without evidence of tolerance at 10 mg 2
• No rebound insomnia observed after discontinuation of 5 or 10 mg doses for up to 12 months 2, 4, 6

Safety Profile

• Adverse events at 5 and 10 mg doses are similar to placebo, with headache being most common (15-18%) 1, 4, 5
• No next-day psychomotor or memory impairment with 5 or 10 mg doses when taken at bedtime 1, 2, 4
• Memory impairment resolves within 2-4 hours after dosing 2
• Risk of next-day amnesia is dose-dependent: 3% with zaleplon vs 1% with placebo 2

Critical Caveats

• Zaleplon should supplement, not replace, Cognitive Behavioral Therapy for Insomnia (CBT-I), which provides superior long-term outcomes 1, 7
• The American Academy of Sleep Medicine provides only a WEAK recommendation for zaleplon due to low-quality evidence and modest clinical benefit 1
• Consider alternative agents (eszopiclone, zolpidem) for patients requiring treatment of both sleep onset and sleep maintenance insomnia 7, 3
• Duration of treatment should be short-term (2-4 weeks), as evidence beyond this period is limited 1, 4, 8