Hydroxyzine Half-Life
The elimination half-life of hydroxyzine in healthy adults is approximately 20 hours, but this is significantly prolonged to 29 hours in elderly patients and 37 hours in patients with hepatic impairment (primary biliary cirrhosis). 1, 2, 3
Half-Life in Different Populations
Healthy Adults
- The mean elimination half-life in healthy adults (mean age ~30 years) is 20.0 ± 4.1 hours after a single oral dose. 1
- Peak serum concentrations occur at approximately 2.1 hours after oral administration. 1
- The volume of distribution is large at 16.0 ± 3.0 L/kg, and clearance is 9.78 ± 3.25 mL/min/kg. 1
Elderly Patients
- The half-life increases by approximately 46% in elderly patients (mean age 69.5 years), extending to 29.3 ± 10.1 hours. 2
- The volume of distribution remains similarly large at 22.5 ± 6.3 L/kg in the elderly. 2
- Clearance is comparable to younger adults at 9.6 ± 3.2 mL/min/kg. 2
- This prolonged half-life necessitates starting at the low end of the dosing range (10 mg at bedtime) in elderly patients due to increased risk of sedation, falls, and anticholinergic effects. 4
Hepatic Impairment
- In patients with primary biliary cirrhosis, the half-life nearly doubles to 36.6 ± 13.1 hours, representing an 83% increase compared to healthy adults. 3
- Peak hydroxyzine levels are higher (116.5 ± 60.6 ng/mL) and occur at 2.3 hours. 3
- Clearance is reduced to 8.65 ± 7.46 mL/min/kg, though the volume of distribution increases to 22.7 ± 13.3 L/kg. 3
- Hydroxyzine must be completely avoided in severe hepatic disease due to excessive sedation risk and impaired elimination. 4, 5
Renal Impairment
- In moderate renal impairment (creatinine clearance 10-20 mL/min), the dose should be reduced by 50%. 4, 5
- In severe renal impairment (creatinine clearance <10 mL/min), hydroxyzine is absolutely contraindicated and should not be administered. 4, 5
Active Metabolite Considerations
- Hydroxyzine is metabolized to cetirizine, an active metabolite with its own antihistaminic properties. 3, 2
- In elderly patients, cetirizine has a half-life of 24.8 ± 7.7 hours, which is not significantly different from the parent compound. 2
- In patients with hepatic impairment, cetirizine's half-life is 25.0 ± 8.2 hours, with peak levels of 500.4 ± 302.0 ng/mL occurring at 4.8 hours. 3
- The prolonged half-lives of both hydroxyzine and its active metabolite contribute to sustained antihistaminic effects lasting 36-144 hours after a single dose. 2, 1
Clinical Implications of Prolonged Half-Life
Dosing Frequency
- The 20-hour half-life in healthy adults supports once-daily dosing at bedtime (10-50 mg) rather than multiple daily doses. 6, 4
- Bedtime dosing provides sustained effects into the next day while minimizing daytime sedation and performance impairment. 4
Accumulation Risk
- With repeated dosing, steady-state is not reached for several days due to the long half-life. 7
- Significant drug accumulation occurs if dosing is more frequent than every 20 hours, particularly in elderly or hepatically impaired patients where the half-life exceeds 29-37 hours. 6, 3, 2
Performance Impairment Duration
- Sedation and performance impairment persist for 36-144 hours after a single dose, even when patients deny subjective drowsiness. 4, 1
- Drivers taking hydroxyzine are 1.5 times more likely to be responsible for fatal automobile accidents due to prolonged cognitive effects. 4
Critical Dosing Algorithm Based on Half-Life
For patients requiring hydroxyzine:
Standard adult dosing: 10-50 mg at bedtime as adjunct to non-sedating antihistamine during the day. 4
Elderly patients (>65 years): Start with 10 mg at bedtime due to 46% longer half-life and increased fall risk. 4, 2
Moderate renal impairment (CrCl 10-20 mL/min): Reduce dose by 50% (e.g., 5-25 mg at bedtime). 4, 5
Severe renal impairment (CrCl <10 mL/min): Absolute contraindication—do not prescribe. 4, 5
Severe hepatic disease: Absolute contraindication—do not prescribe due to 83% longer half-life. 4, 3