What are the guidelines for prescribing ZOLPIDEM (zolpidem) to a patient with a history of substance abuse, respiratory disease, or liver impairment for the treatment of insomnia?

Zolpidem Prescribing in Special Populations: Substance Abuse, Respiratory Disease, and Liver Impairment

Zolpidem can be prescribed cautiously in patients with substance abuse history, respiratory disease, or liver impairment, but requires specific dose adjustments and heightened monitoring—particularly a mandatory 5 mg dose for hepatic impairment and avoidance in severe liver disease, while respiratory disease and substance abuse history warrant careful risk-benefit assessment rather than absolute contraindication. 1

Liver Impairment: Mandatory Dose Reduction

Patients with mild to moderate hepatic impairment must receive only 5 mg once daily immediately before bedtime, as they clear zolpidem more slowly than normal subjects. 1

• Severe hepatic impairment is a contraindication—avoid zolpidem entirely as it may contribute to encephalopathy. 1
• The reduced clearance in hepatic impairment increases drug exposure and risk of next-day impairment, making the standard 10 mg dose dangerous. 1
• No dose escalation should be attempted in patients with any degree of liver disease. 1

Substance Abuse History: Proceed with Extreme Caution

Zolpidem is a federally controlled substance (C-IV) with documented abuse and dependence potential, requiring careful screening before prescribing to patients with substance abuse history. 1

• The FDA medication guide explicitly states that healthcare providers must be informed if patients "have ever abused or have been dependent on alcohol, prescription medicines or street drugs." 1
• While zolpidem appears to have lower abuse potential compared to benzodiazepines based on older data 2, 3, more recent evidence documents withdrawal seizures occurring at doses as low as 160 mg/day (though most cases involved 450-600 mg/day). 4
• Consider as-needed dosing (3-5 times per week) rather than nightly use to reduce dependence risk while maintaining efficacy—this approach reduces sleep onset latency by 15 minutes and increases total sleep time by 48 minutes on nights taken. 5
• Tolerance has been described in patients taking high dosages for extended periods, though not typically at recommended doses for short-term use. 2

Monitoring Strategy for Substance Abuse Risk

• Limit initial prescriptions to 7-10 days and reassess before refilling. 1
• Explicitly counsel patients that zolpidem "can be abused or lead to dependence" and must be kept in a safe place. 1
• Avoid combining with alcohol or other CNS depressants, as this increases abuse potential and risk of complex sleep behaviors. 1

Respiratory Disease: Use with Heightened Vigilance

The FDA medication guide advises caution in patients with "lung disease or breathing problems," though this is not an absolute contraindication. 1

• Zolpidem's CNS depressant effects can potentially worsen respiratory function, particularly when combined with other sedating medications. 1
• Start with the lowest effective dose (5 mg) in patients with respiratory compromise. 1
• Breastfeeding infants exposed to zolpidem should be monitored for "excess sedation, hypotonia, and respiratory depression," indicating the drug's respiratory depressant potential. 1
• Avoid combining zolpidem with other CNS depressants in respiratory disease patients, as "dosage adjustment may be necessary when combined with other CNS-depressant drugs because of the potentially additive effects." 1

Special Considerations for Sleep Apnea

• While not explicitly contraindicated, exercise extreme caution in obstructive sleep apnea (OSA) patients, as sedative-hypnotics can worsen upper airway obstruction.
• Consider polysomnography before prescribing if undiagnosed sleep apnea is suspected, as "insomnia not remitting within 7-10 days requires further evaluation" for underlying sleep disorders. 6

Universal Prescribing Safeguards Across All Special Populations

All patients, regardless of comorbidities, must receive specific safety counseling about complex sleep behaviors that have caused serious injury and death. 1

• Complex sleep behaviors (sleep-driving, sleep-eating, sleepwalking) can occur even at recommended doses and have been documented regardless of dose, age, or medical history. 4, 1
• Patients must be instructed to take zolpidem only when able to remain in bed for 7-8 hours and immediately before bedtime, not sooner. 1
• Taking zolpidem with or immediately after meals delays effectiveness and should be avoided. 1
• Women require lower doses (5 mg immediate-release, 6.25 mg extended-release) due to 45% higher drug exposure compared to men. 1, 5

Dosing Algorithm for Special Populations

For patients with ANY of these conditions:

1. Hepatic impairment (mild-moderate): 5 mg only, no escalation permitted 1
2. Severe hepatic impairment: Do not prescribe 1
3. Substance abuse history: Start 5 mg, consider as-needed dosing (3-5×/week), limit duration 5, 1
4. Respiratory disease: Start 5 mg, avoid CNS depressant combinations 1
5. Elderly patients: 5 mg regardless of other factors 1
6. Female patients: 5 mg immediate-release or 6.25 mg extended-release 1

If multiple risk factors coexist (e.g., elderly woman with liver disease and substance abuse history), the 5 mg dose applies with enhanced monitoring and shortest possible treatment duration.

Common Pitfalls to Avoid

• Never prescribe 10 mg to patients with hepatic impairment—this is explicitly contraindicated and increases encephalopathy risk. 1
• Never assume "low abuse potential" means no risk—withdrawal seizures and dependence are documented. 4
• Never combine with alcohol—this dramatically increases risk of complex sleep behaviors and respiratory depression. 1
• Never prescribe without counseling about complex sleep behaviors—patients must understand they may engage in activities while not fully awake. 1
• Never continue beyond 4-5 weeks without reassessment—FDA approval is for short-term use only, and persistent insomnia suggests underlying sleep disorders requiring evaluation. 6, 1

Efficacy Expectations at Reduced Doses

• The 5 mg dose reduces sleep onset latency by approximately 10-15 minutes compared to placebo. 5
• Total sleep time increases by 23-29 minutes with standard formulation. 5
• Effects are evident from the first night of treatment. 5
• The American Academy of Sleep Medicine found weak evidence of efficacy but determined benefits marginally outweigh harms when used appropriately. 7