What is the half-life of hydroxyzine?

Half-Life of Hydroxyzine

The elimination half-life of hydroxyzine is approximately 20 hours in healthy adults, though this can be significantly prolonged to 36.6 hours in patients with hepatic dysfunction such as primary biliary cirrhosis. 1, 2

Pharmacokinetic Parameters in Different Populations

Healthy Adults

• Elimination half-life: approximately 20 hours 1
• Total body clearance: 5-12 mL/min/kg 1
• Apparent volume of distribution: exceeds 4 L/kg, with some studies showing values as high as 22.7 L/kg 1, 2
• Peak plasma concentrations occur at 2-3 hours after oral administration 1

Pediatric Patients

• Children have shorter elimination half-lives compared to adults, though specific values vary 1, 3
• The guideline for brain death determination in children lists hydroxyzine with a half-life range in infants/children, acknowledging age-dependent variability 4

Patients with Hepatic Impairment

• In patients with primary biliary cirrhosis, the mean elimination half-life extends to 36.6 ± 13.1 hours (nearly double that of healthy adults) 2
• Clearance is reduced to 8.65 ± 7.46 mL/min/kg in these patients 2
• Volume of distribution increases to 22.7 ± 13.3 L/kg 2

Patients with Renal Impairment

• Dose reduction by half is recommended in patients with moderate to severe renal impairment 4
• Hydroxyzine should be avoided in severe renal impairment (creatinine clearance < 10 mL/min) 4

Clinical Implications

Dosing Frequency

• The relatively long half-life of approximately 20 hours suggests hydroxyzine can be administered once daily in adults, though traditional dosing is often divided (e.g., 25 mg four times daily for urticaria) 4, 1
• When used as a nighttime sedating antihistamine, typical doses range from 10-50 mg 4

Time to Steady State and Washout

• Complete elimination requires 5-7 half-lives, meaning hydroxyzine may remain in the body for approximately 4-7 days in healthy adults (100-140 hours) 1
• In patients with hepatic dysfunction, this extends to 7-10 days or longer 2
• Steady-state concentrations are reached after several days of regular dosing 3

Active Metabolite Considerations

• Cetirizine is the active metabolite of hydroxyzine with its own pharmacologic activity 4, 2
• In patients with primary biliary cirrhosis, cetirizine has a mean elimination half-life of 25.0 ± 8.2 hours 2
• Peak cetirizine levels occur at approximately 4.8 hours after hydroxyzine administration 2

Important Clinical Caveats

Sedation and CNS Effects

• Hydroxyzine causes sedation in approximately 80% of patients, the highest rate among first-generation antihistamines 4
• All patients in the hepatic dysfunction study became sleepy for 0.5-6 hours after dosing 2
• The prolonged half-life means sedative effects can persist well beyond the initial dosing period 1

Drug Testing Considerations

• Antihistamine suppression of skin testing can persist for extended periods due to the long half-life 2
• In patients with hepatic dysfunction, wheal suppression lasted 1-120 hours and flare suppression lasted 1-144 hours after a single dose 2

Special Populations Requiring Caution

• Older adults are at high risk for anticholinergic side effects including prostatic hypertrophy complications, elevated intraocular pressure, and cognitive impairment 4
• The long half-life increases accumulation risk with repeated dosing, particularly in elderly patients 3