What is the maximum daily dose of hydroxyzine (hydroxyzine pamoate) for an adult patient with potential impaired renal or hepatic function?

Maximum Daily Dose of Hydroxyzine Pamoate

The maximum daily dose of hydroxyzine pamoate for adults with normal renal and hepatic function is 100 mg per day (50 mg twice daily), and this dose must be reduced by half in patients with impaired renal or hepatic function. 1

Standard Dosing in Adults with Normal Function

• The typical therapeutic dose for hydroxyzine in generalized anxiety disorder is 50 mg per day, which has demonstrated both efficacy and safety in controlled trials 2, 3
• For urticaria and allergic conditions, hydroxyzine can be dosed at 10-50 mg at night when used as an adjunct to daytime non-sedating antihistamines 1
• Studies have evaluated hydroxyzine at 50 mg once daily at bedtime as an optimal dosing strategy that maintains antihistamine efficacy while minimizing daytime sedation and psychomotor impairment 4

Critical Dose Adjustments for Renal Impairment

In patients with moderate renal impairment (creatinine clearance 10-20 mL/min), the dose of hydroxyzine must be reduced by half. 1

• Hydroxyzine should be avoided entirely in severe renal impairment (creatinine clearance <10 mL/min) 1
• The elimination half-life of hydroxyzine is approximately 20 hours in adults with normal renal function, but becomes greatly prolonged in chronic renal disease, necessitating dose reduction 5
• Hydroxyzine is primarily metabolized hepatically with extensive first-pass metabolism, but renal excretion of metabolites means accumulation occurs with renal dysfunction 5

Critical Dose Adjustments for Hepatic Impairment

Hydroxyzine should be avoided in severe liver disease because its sedating effects are inappropriate and potentially dangerous in this population. 1

• The drug undergoes extensive hepatic metabolism, and liver disease can significantly prolong elimination and increase toxicity risk 1
• In patients with mild to moderate hepatic impairment who require hydroxyzine, use the lowest effective dose with close monitoring for excessive sedation and other adverse effects 1

Practical Dosing Algorithm

For patients with impaired renal or hepatic function:

1. Assess renal function (creatinine clearance) and hepatic function (liver enzymes, clinical signs of liver disease)
2. If CrCl 10-20 mL/min: Reduce dose to 25 mg daily (half the standard dose) 1
3. If CrCl <10 mL/min: Avoid hydroxyzine entirely 1
4. If severe hepatic impairment: Avoid hydroxyzine entirely 1
5. If mild-moderate hepatic impairment: Start with 10-25 mg daily and monitor closely 1

Common Pitfalls to Avoid

• Do not exceed 100 mg daily in any adult patient, even those with normal organ function, as higher doses increase risk of sedation and anticholinergic effects without additional therapeutic benefit 1, 2, 3
• Do not use standard adult doses in elderly patients (≥65 years), as they often have age-related decline in renal function requiring dose reduction 1
• Avoid divided dosing (e.g., 25 mg twice daily) when possible, as bedtime dosing of 50 mg provides comparable efficacy with reduced daytime sedation and psychomotor impairment 4
• Monitor for excessive sedation as the primary indicator of potential toxicity, especially in the first week of therapy when drowsiness is most pronounced 2, 6
• Do not assume tolerance develops to sedative effects—studies show that objective psychomotor impairment persists throughout 5 days of hydroxyzine administration without development of tolerance 6

Safety Considerations in Special Populations

• Pregnancy: Hydroxyzine is specifically contraindicated in early pregnancy according to UK product information, making it the only antihistamine with this explicit contraindication 1
• Elderly patients: Consider starting at lower doses due to age-related decline in renal function and increased sensitivity to anticholinergic and sedative effects 1
• Drug interactions: Hydroxyzine's sedative effects are potentiated by alcohol, benzodiazepines, and other CNS depressants—counsel patients accordingly 1