Can a patient take Ambien (zolpidem) after taking hydroxyzine at midnight?

Can a Patient Take Ambien After Hydroxyzine at Midnight?

No, a patient should not take Ambien (zolpidem) shortly after taking hydroxyzine at midnight due to the significant risk of additive CNS depression, next-day impairment, and potentially dangerous sedation.

Primary Safety Concern: Additive CNS Depression

The FDA labeling for both medications explicitly warns against this combination:

• Hydroxyzine's FDA label states: "THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS... Therefore, when central nervous system depressants are administered concomitantly with hydroxyzine their dosage should be reduced." 1

• Zolpidem's FDA label warns: "Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression... Dosage adjustments of zolpidem tartrate and of other concomitant CNS depressants may be necessary when zolpidem tartrate is administered with such agents because of the potentially additive effects." 2

Specific Risks of This Combination

Enhanced Sedation and Impairment

• Both medications cause significant sedation that persists beyond their plasma half-lives, with end-organ effects lasting longer than expected 3
• Hydroxyzine causes drowsiness and performance impairment that can occur without subjective awareness, meaning patients may feel alert while being functionally impaired 3
• Morning doses of hydroxyzine 50 mg caused more prominent impairment than evening doses across multiple cognitive domains, demonstrating that sedative effects persist well into the following day 4

Next-Day Safety Hazards

• The combination significantly increases fall risk, particularly in elderly patients, as zolpidem causes "drowsiness and a decreased level of consciousness" making "patients, particularly the elderly, at higher risk of falls" 2
• Drivers taking first-generation antihistamines like hydroxyzine are 1.5 times more likely to be responsible for fatal automobile accidents 3
• Zolpidem alone is associated with increased fracture risk (adjusted odds ratio 1.72) and major head injury requiring hospitalization (adjusted hazard ratio 1.67) 3

Complex Sleep Behaviors

• Zolpidem can cause dangerous complex sleep behaviors (sleep-walking, sleep-driving) that "may occur with zolpidem tartrate alone at recommended doses, with or without the concomitant use of alcohol or other CNS depressants" 2
• The risk of these potentially fatal behaviors is explicitly increased when zolpidem is combined with other CNS depressants 2

Clinical Recommendations

If Sleep Aid Is Urgently Needed

• Wait a minimum of 8-12 hours after hydroxyzine administration before considering zolpidem, as hydroxyzine's sedative effects and metabolites have prolonged plasma half-lives 3
• If zolpidem must be used, reduce the dose to 5 mg (half the standard adult dose) per FDA guidance on CNS depressant combinations 2
• Ensure the patient can remain in bed for a full 7-8 hours after zolpidem administration 2

Safer Alternatives

• Consider non-pharmacologic interventions such as cognitive behavioral therapy for insomnia, which is effective for sleep disturbances 3
• If pharmacologic treatment is necessary, use a single agent rather than combining sedating medications 3
• The guideline recommendation against combining a sedating antihistamine at night with another agent specifically notes this strategy "is not a preferred strategy for avoiding daytime drowsiness and performance impairment" 3

Special Population Considerations

Elderly Patients

• Elderly patients are "more sensitive to the psychomotor impairment promoted by first-generation antihistamines, are at increased risk for complications such as fractures and subdural hematomas caused by falls" 3
• Hydroxyzine's FDA label specifically warns that "sedating drugs may cause confusion and over sedation in the elderly; elderly patients generally should be started on low doses of hydroxyzine and observed closely" 1
• If combination is unavoidable, use zolpidem 5 mg maximum in elderly patients 2

Patients with Cardiac Risk Factors

• Hydroxyzine can cause QT prolongation and should be used cautiously with other medications that may affect cardiac conduction 1
• Avoid this combination entirely in patients with pre-existing heart disease, electrolyte imbalances, or concomitant arrhythmogenic drug use 1

Critical Warning Signs

Instruct patients to seek immediate medical attention if they experience: 2

• Difficulty breathing or respiratory depression
• Extreme confusion or inability to awaken
• Complex sleep behaviors (sleep-walking, sleep-driving)
• Severe next-day impairment affecting safety