What is the recommended dosing schedule for zolpidem (Ambien) in adults, particularly for elderly patients or those with hepatic impairment, for the treatment of insomnia?

Zolpidem Dosing Schedule

The FDA-recommended starting dose is 5 mg for women and 5-10 mg for men taken once nightly immediately before bedtime, with elderly or hepatically impaired patients starting at 5 mg regardless of sex. 1

Standard Adult Dosing

• Women should receive 5 mg as the initial dose due to 45% slower drug clearance compared to men, resulting in higher blood levels and increased risk of next-morning impairment 1
• Men should start with either 5 mg or 10 mg, with the choice based on severity of insomnia 1
• If 5 mg proves ineffective in either sex, the dose may be increased to 10 mg, though this carries higher risk of next-day driving impairment 1
• The maximum dose is 10 mg once daily—never exceed this or redose during the same night 1

Special Population Dosing

Elderly Patients (≥65 years)

• Use 5 mg once daily regardless of sex due to increased sensitivity to zolpidem's sedative effects 1
• Elderly patients experience higher rates of dizziness (3% vs 0% placebo), drowsiness (5% vs 2%), and falls, particularly at doses exceeding 10 mg 1
• In non-U.S. trials, 93% of fall reports occurred in patients ≥70 years, with 82% receiving doses >10 mg 1

Hepatic Impairment

• Mild to moderate hepatic impairment: 5 mg once daily due to reduced drug clearance 1
• Severe hepatic impairment: avoid zolpidem entirely as it may contribute to encephalopathy 1

Debilitated Patients

• Use 5 mg once daily due to heightened sensitivity to CNS effects 1

Administration Guidelines

• Take immediately before bedtime with at least 7-8 hours remaining before planned awakening 1
• Administer on an empty stomach—taking with or immediately after meals delays absorption and reduces effectiveness 2, 1
• Single dose only per night—do not readminister if awakening occurs 1

Formulation-Specific Dosing

Extended-Release Formulation

• Women: 6.25 mg 2
• Men: 6.25-12.5 mg 2
• The FDA reduced recommended starting doses from 12.5 mg to 6.25 mg due to next-day impairment concerns 3, 2
• Extended-release is more effective for sleep maintenance, reducing wake-after-sleep-onset by 25 minutes 2

Sublingual Low-Dose (Middle-of-Night Awakening)

• 3.5 mg as needed when difficulty returning to sleep after middle-of-night awakening 2
• Requires at least 4 hours remaining before planned awakening 4

Oral Spray

• Adults: 10 mg (two 5 mg sprays) 4
• Elderly/debilitated: 5 mg (one spray) 4

Concomitant CNS Depressants

• Reduce zolpidem dose when combining with other CNS depressants due to additive effects 1
• Never combine with alcohol 2

Expected Clinical Effects

• Reduces sleep onset latency by 10-15 minutes compared to placebo 2, 5
• Increases total sleep time by 23-29 minutes with immediate-release formulation 2, 5
• Effects are evident from the first night of treatment 2
• Peak plasma concentration occurs in 45-60 minutes with elimination half-life of 2.4 hours 5

Critical Safety Warnings

• Risk of complex sleep behaviors including sleep-driving, sleep-eating, and sleepwalking 2
• Next-morning impairment is dose-dependent, particularly problematic with 10 mg dose in women 1
• Avoid during pregnancy and breastfeeding; if breastfeeding, interrupt for 23 hours (5 elimination half-lives) after administration 2, 1
• Use caution in respiratory conditions including asthma, COPD, and sleep apnea 2

Duration and Discontinuation

• FDA indication is for short-term use (≤4 weeks) 6
• Long-term studies up to 6 months show maintained efficacy without tolerance development at recommended doses 6, 7
• Consider intermittent dosing (2-3 nights per week rather than nightly) to reduce tolerance risk 2
• Abrupt discontinuation may produce withdrawal symptoms—taper if used chronically 2
• Minimal rebound insomnia when discontinued after recommended use 6, 7

Common Pitfalls to Avoid

• Do not use 10 mg as starting dose in women—this is the most common dosing error given FDA's 2013 mandate 1
• Do not prescribe to patients who cannot dedicate 7-8 hours to sleep, as this dramatically increases next-day impairment risk 1
• Do not overlook hepatic function—even mild impairment requires dose reduction 1
• Do not assume elderly men can tolerate higher doses—age trumps sex for dosing decisions 1