Can a patient take hydroxyzine after taking Ativan (lorazepam) 12 hours ago, having also taken metronidazole (an antibiotic) and famotidine (an H2 receptor antagonist) yesterday?

Can the Patient Take Hydroxyzine After Ativan 12 Hours Ago?

Yes, the patient can take hydroxyzine 12 hours after taking Ativan (lorazepam), but the dose of hydroxyzine should be reduced due to the potentiating effects on CNS depression. 1

Critical Drug Interaction Considerations

CNS Depression Potentiation

• The FDA label explicitly warns that hydroxyzine potentiates the action of central nervous system depressants including narcotics, non-narcotic analgesics, and barbiturates, and therefore when CNS depressants are administered concomitantly with hydroxyzine, their dosage should be reduced. 1

• While 12 hours provides some temporal separation, lorazepam has a half-life of approximately 12-18 hours, meaning significant drug levels remain in the system. 1

• The FDA specifically cautions that patients should be warned against simultaneous use of other CNS depressant drugs and that the effects of alcohol may be increased. 1

Recommended Dosing Strategy

• Start with hydroxyzine 25 mg rather than the standard 50 mg dose when there is recent benzodiazepine use. 2

• Guidelines recommend 25-50 mg of hydroxyzine at bedtime when used for pruritus or anxiety, but the lower end of this range is appropriate given the recent lorazepam exposure. 2

• Research demonstrates that hydroxyzine 25 mg provides anxiolytic benefit with less daytime sleepiness compared to 50 mg dosing. 3

Interactions with Other Medications

Metronidazole

• No significant interaction exists between hydroxyzine and metronidazole - these medications can be safely combined. 1

• Metronidazole is not listed among the drugs that prolong QT interval or interact with hydroxyzine's metabolism. 1

Famotidine

• Famotidine (an H2 receptor antagonist) is actually complementary to hydroxyzine (an H1 receptor antagonist) and represents a rational therapeutic combination for histamine-mediated conditions. 4

• The combination of H1 and H2 antihistamines works synergistically - H1 blockers reduce skin symptoms (flushing, itching) and tachycardia, while H2 blockers specifically target gastrointestinal symptoms. 4

• This combination is safe with minimal significant risks in most adults. 4

Important Safety Warnings

QT Prolongation Risk

• Hydroxyzine carries a risk of QT prolongation and Torsade de Pointes, particularly in patients with pre-existing heart disease, electrolyte imbalances, or concomitant arrhythmogenic drug use. 1

• Use caution if the patient has risk factors for QT prolongation, congenital long QT syndrome, recent myocardial infarction, uncompensated heart failure, or bradyarrhythmias. 1

Cognitive and Performance Impairment

• Hydroxyzine causes significant sedation (80% sedation rates) and significantly prolongs reaction times even at 25 mg twice daily dosing. 2

• Patients should be warned against driving or operating dangerous machinery while taking hydroxyzine. 1

• Performance impairment can exist without subjective awareness of drowsiness. 5

• Morning doses of hydroxyzine cause more prominent cognitive impairment than evening doses, affecting performance on divided attention tasks and attention network tests. 6

Clinical Algorithm for Administration

1. Verify the time since last lorazepam dose - if truly 12 hours, proceed with reduced hydroxyzine dosing. 1

2. Start with hydroxyzine 25 mg at bedtime rather than 50 mg to minimize additive CNS depression. 2, 3

3. Warn the patient about enhanced sedation and advise against driving, operating machinery, or consuming alcohol. 1

4. Monitor for excessive sedation over the next 24 hours, particularly if another lorazepam dose is planned. 1

5. Consider avoiding hydroxyzine entirely if the patient needs to take lorazepam regularly or if cognitive performance is critical. 2

Special Population Considerations

• If the patient is elderly (≥65 years), start at an even lower dose or avoid hydroxyzine entirely due to increased risk of sedation, anticholinergic effects, and cognitive impairment. 1

• Elderly patients are more likely to have decreased renal function, and hydroxyzine should be used cautiously with dose selection at the low end of the range. 1

• Sedating drugs may cause confusion and over-sedation in the elderly. 1

Common Pitfalls to Avoid

• Do not use the standard 50 mg dose of hydroxyzine when benzodiazepines are in the system - this significantly increases risk of excessive sedation and cognitive impairment. 1, 2

• Do not assume the patient is safe to drive or work even if they deny feeling drowsy - performance impairment occurs without subjective awareness. 5

• Do not combine hydroxyzine with other CNS depressants including alcohol without explicit warning about potentiation effects. 1

• Do not use hydroxyzine for prolonged monotherapy due to performance concerns - it is best used short-term or at bedtime only. 2