Pre-Prescribing Requirements for Ambien (Zolpidem)
Before prescribing Ambien, you must assess for contraindications including severe hepatic impairment, pregnancy/breastfeeding status, respiratory conditions (asthma, COPD, sleep apnea), concurrent CNS depressant use, and history of complex sleep behaviors—then determine the appropriate sex-specific and age-specific starting dose. 1
Mandatory Pre-Prescription Assessments
Medical History Screening
- Screen for severe hepatic impairment - zolpidem is contraindicated in severe liver disease as it may contribute to encephalopathy; patients with mild-to-moderate impairment require dose reduction to 5 mg 1
- Evaluate respiratory function - use caution in patients with asthma, COPD, or sleep apnea due to risk of respiratory depression 2, 1
- Assess for psychiatric conditions - zolpidem increases suicide risk (OR 2.08) regardless of pre-existing psychiatric illness, and causes hallucinations in some patients 3
- Review medication list - identify concurrent CNS depressants or alcohol use, as combination increases sedation and respiratory depression risk 2
Patient-Specific Risk Factors
- Determine sex - women clear zolpidem 45% slower than men, resulting in blood levels approximately 45% higher at equivalent doses, necessitating lower starting doses 2, 1
- Assess age - elderly patients (≥65 years) require 5 mg regardless of sex due to increased sensitivity and fall risk 1
- Screen for pregnancy/lactation status - zolpidem is FDA Category C; maternal use increases risk of low birth weight (OR 1.39), preterm delivery (OR 1.49), and cesarean delivery (OR 1.74) 3. If breastfeeding, counsel on pumping and discarding milk for 23 hours post-dose 1
- Evaluate fall risk - zolpidem increases fall risk with OR of 4.28 in hospitalized patients and hip fracture risk (RR 1.92), particularly in elderly 3
History of Sleep-Related Behaviors
- Screen for prior complex sleep behaviors - assess history of sleepwalking, sleep-eating, or sleep-driving, as the FDA has issued warnings about these occurring with zolpidem regardless of dose, age, or prior history 2, 3
Correct Dosing Based on Patient Characteristics
Sex-Specific Dosing (Critical)
- Women: Start with 5 mg immediate-release or 6.25 mg extended-release - the FDA mandated this reduction in 2013 due to next-morning driving impairment and psychomotor dysfunction at 10 mg doses 2, 1
- Men: Start with 5-10 mg immediate-release or 6.25-12.5 mg extended-release 2, 1
- Common prescribing error: Approximately 50% of female veterans continued receiving high doses after the 2013 FDA mandate, representing a critical safety gap 2
Age-Specific Dosing
- Elderly patients (≥65 years): 5 mg once daily regardless of sex to minimize adverse effects related to impaired motor/cognitive performance 1
- Pediatric patients: Not recommended - zolpidem is not approved for patients under 18 years; studies showed no efficacy and 23.5% experienced dizziness and 7% had hallucinations 1
Hepatic Impairment Dosing
- Mild-to-moderate impairment: 5 mg once daily immediately before bedtime 1
- Severe impairment: Avoid zolpidem entirely due to encephalopathy risk 1
Administration Instructions to Provide
- Take on empty stomach immediately before bedtime - food delays absorption and reduces effectiveness 2
- Ensure 7-8 hours available for sleep - to minimize next-day impairment risk 2, 1
- Avoid alcohol and other CNS depressants during treatment 2
- Do not take with or after meals as this delays drug effect 2
Special Considerations for Ongoing Management
Consider As-Needed Dosing Strategy
- Intermittent dosing (2-3 nights per week or as-needed) reduces drug exposure and dependence risk while maintaining efficacy, with moderate evidence showing 15-minute reduction in sleep onset latency and 48-minute increase in total sleep time on nights taken 4, 2
Combine with Non-Pharmacologic Therapy
- Recommend cognitive behavioral therapy for insomnia (CBT-I) in conjunction with zolpidem to minimize needed dose and duration 2