What is the maximum recommended dose of extended-release Ambien (zolpidem) for adult men and women, considering factors such as sex, age, and hepatic impairment?

Maximum Dose of Extended-Release Ambien

The maximum recommended dose of extended-release zolpidem is 12.5 mg for men and 6.25 mg for women, taken once nightly immediately before bedtime. 1

Sex-Specific Dosing Requirements

Women require lower doses due to 45% slower drug clearance compared to men, resulting in higher blood levels and increased risk of next-day impairment. 1, 2

• Women: Maximum 6.25 mg extended-release 2, 1
• Men: Maximum 12.5 mg extended-release 2, 1

The FDA mandated these sex-specific doses in 2013 after discovering that higher morning blood levels caused next-day driving impairment, particularly in women. 3

Special Population Dosing

Elderly Patients (≥65 years)

• Maximum dose: 5 mg once daily regardless of sex 1
• Elderly patients have increased sensitivity to zolpidem's effects and higher fall risk 1
• In non-U.S. trials, 93% of falls occurred in patients ≥70 years, with 82% taking doses >10 mg 1

Hepatic Impairment

• Mild to moderate hepatic impairment: Maximum 5 mg once daily 1
• Severe hepatic impairment: Avoid zolpidem entirely as it may contribute to encephalopathy 1

Clinical Efficacy Evidence

Extended-release zolpidem 12.5 mg demonstrates moderate reduction in sleep onset latency and wake time after sleep onset, though the evidence quality is low due to imprecision and potential publication bias. 4

• The 12.5 mg dose shows benefits that outweigh minimal potential harms 2
• The 6.25 mg dose has minimal and inconclusive efficacy data, with benefits and harms judged approximately equal 4
• Extended-release formulation reduces wake time after sleep onset by 25 minutes compared to placebo 2

Critical Safety Warnings

Never exceed the maximum recommended doses, as higher doses significantly increase adverse effects:

• Doses >10 mg in elderly patients (≥70 years) were associated with 78% of confusion cases in clinical trials 1
• Common adverse effects include amnesia, dizziness, somnolence, nausea, and altered taste 4
• Complex sleep behaviors (sleep-driving, sleepwalking, sleep-eating) can occur at any dose 2

Common Prescribing Pitfalls

Approximately 50% of women continued receiving high-dose prescriptions (>6.25 mg extended-release) after the 2013 FDA mandate, representing widespread non-adherence to safety guidelines. 3

• Do not prescribe 12.5 mg extended-release to women 3
• Do not prescribe >5 mg to elderly patients regardless of formulation 1
• Do not prescribe any dose to patients with severe hepatic impairment 1

Administration Guidelines

• Take immediately before bedtime on an empty stomach 2
• Do not take with or immediately after meals, as this delays drug effect 2
• Avoid combining with alcohol or other CNS depressants 2
• Ensure at least 7-8 hours available for sleep before required awakening 2