Contraindications to Ambien (Zolpidem)
Zolpidem is absolutely contraindicated in two specific situations: patients who have experienced complex sleep behaviors (such as sleep-walking, sleep-driving, or engaging in other activities while not fully awake) after taking zolpidem, and patients with known hypersensitivity to zolpidem including anaphylaxis or angioedema. 1
Absolute Contraindications
Complex Sleep Behaviors
- Patients who have experienced any complex sleep behavior after taking zolpidem must never receive the medication again. 1
- Complex sleep behaviors include:
- These behaviors can occur after the first dose or any subsequent dose, regardless of whether alcohol or other CNS depressants are used concurrently 1
- These events have resulted in serious injuries and death, making this an absolute contraindication. 1
- Patients typically have no memory of these events 1
Hypersensitivity Reactions
- Known hypersensitivity to zolpidem is an absolute contraindication. 1
- Observed reactions include:
- These reactions can occur after the first or subsequent doses 1
Critical Warnings and Relative Contraindications
Pregnancy and Nursing
- All obesity medications including zolpidem are contraindicated in individuals who are pregnant or actively trying to conceive. 2
- Zolpidem is not recommended for use in individuals who are nursing 2
- The FDA has classified zolpidem as category C based on adverse outcomes in animal fetal development 3
- Maternal exposure to zolpidem has been associated with increased incidence of low birth weight (OR = 1.39), preterm delivery (OR 1.49), small for gestational age babies (OR = 1.34), and cesarean deliveries (OR = 1.74) 3
High-Risk Populations Requiring Extreme Caution
Elderly Patients:
- Benzodiazepines and zolpidem should be avoided in older patients and those with cognitive impairment due to risk of decreased cognitive performance 2, 4
- Elderly patients are at higher risk of falls due to drowsiness and decreased level of consciousness caused by zolpidem 1
- When zolpidem must be used in elderly patients, the dose must be reduced to 5 mg immediate-release or 6.25 mg extended-release 5
Patients with Cognitive Impairment:
- Regular use of benzodiazepines and similar agents like zolpidem can lead to tolerance, addiction, depression, and cognitive impairment 2
- A case series demonstrated that 80.8% of adverse drug reactions in patients aged 50 or older were CNS-related, including confusion, dizziness, and daytime sleepiness 3
Patients Taking Other CNS Depressants:
- Coadministration with other CNS depressants (benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression and is relatively contraindicated 1
- The combination increases risk of next-day psychomotor impairment, including impaired driving 1
- Avoid combining with other sedative-hypnotics at bedtime or middle of the night 1
Patients with Hepatic Impairment:
- Patients with hepatic impairment require reduced dosing (5 mg immediate-release or 6.25 mg extended-release) 5
- Caution should be exercised when prescribing to elderly patients with hepatic impairment 6
Common Pitfalls to Avoid
- Do not prescribe zolpidem if less than a full night of sleep (7-8 hours) is available, as this significantly increases the risk of next-day psychomotor impairment 1
- Never exceed recommended doses: Women should receive maximum 5 mg immediate-release or 6.25 mg extended-release; men should receive maximum 10 mg immediate-release or 12.5 mg extended-release 5
- Do not ignore the 7-10 day rule: If insomnia does not remit after 7-10 days of treatment, this may indicate a primary psychiatric or medical illness requiring further evaluation 1, 4
- Avoid long-term continuous use: Zolpidem is FDA-approved for short-term use only (4-5 weeks), and long-term use leads to tolerance 4
- Screen for suicide risk: Suicide attempts and completion have been linked with zolpidem use (OR 2.08; 95% CI 1.83-2.63) regardless of comorbid psychiatric illness 3