What are the dosing guidelines, contraindications, and common adverse effects of hydroxyzine for anxiety and pruritus in adults and children?

Hydroxyzine: Dosing, Contraindications, and Adverse Effects

Definitive Dosing Guidelines

For anxiety in adults, hydroxyzine should be dosed at 50-100 mg four times daily, while for pruritus the dose is 25 mg three to four times daily, with bedtime dosing preferred to minimize daytime sedation and psychomotor impairment. 1

Adult Dosing

• Anxiety management: 50-100 mg four times daily (QID), though guidelines suggest a practical range of 10-50 mg per dose 1, 2
• Pruritus: 25 mg three to four times daily (TID or QID), with 25-50 mg at bedtime being particularly beneficial due to sedative properties 1, 3
• Premedication/sedation: 50-100 mg as a single dose 1

Pediatric Dosing

• Children under 6 years: 50 mg daily in divided doses for both anxiety and pruritus 1
• Children over 6 years: 50-100 mg daily in divided doses for both anxiety and pruritus 1
• Hydroxyzine is approved for anxiolytic therapy in children in both Europe and the United States, available in tablet and syrup formulations 2

Dosing Strategy to Minimize Adverse Effects

• Bedtime dosing is strongly preferred as it maintains antihistamine efficacy while mitigating daytime psychomotor impairment and reaction time degradation 4, 2
• For urticaria with sleep disturbances, combine a non-sedating antihistamine during the day with hydroxyzine 10-50 mg at bedtime 2

Absolute Contraindications

Hydroxyzine is absolutely contraindicated in early pregnancy, severe renal impairment, severe liver disease, and when co-administered with other anxiolytic agents like benzodiazepines. 2, 3

Specific Contraindications

• Early pregnancy: Specifically contraindicated per UK manufacturer's guidelines 3, 2
• Severe renal impairment: Should be avoided entirely 2
• Severe liver disease: Avoided due to inappropriate sedating effects 3, 2
• Concurrent anxiolytic use: Co-administration with benzodiazepines is contraindicated due to heightened risk of additive CNS depression 2
• Elderly patients with pruritus: Should not be prescribed due to increased risk of falls, fractures, and anticholinergic side effects 2

Dose Adjustments Required

• Moderate renal impairment: Dose should be halved 2, 3
• Elderly patients: Start with lower doses and monitor closely for psychomotor impairment and fall risk 2

Common and Serious Adverse Effects

Central Nervous System Effects

• Significant sedation is the most prominent adverse effect, impairing driving ability, work performance, and cognitive function 2
• Drivers taking first-generation antihistamines like hydroxyzine are 1.5 times more likely to be involved in fatal motor vehicle accidents 2
• Performance impairment can occur without subjective awareness of drowsiness, and worsens with concurrent activities like cell phone use 2
• Drowsiness, dry mouth, and irritability are significant even with bedtime dosing 4

Cardiovascular Effects

• Supraventricular tachycardia has been reported in pediatric patients on clinical doses 5

Long-Term Neurodevelopmental Concerns

• Repeat prescriptions in preschool children (under age 5) are associated with significantly higher rates of tics (OR 1.55), anxiety disorders (OR 1.34), and conduct disturbances (OR 1.34) by age 10 6
• The shortest possible duration should be used in preschool-age children given these potential long-term neurodevelopmental effects 6

Anticholinergic Effects

• Dry mouth, constipation, and urinary retention are common, particularly in elderly patients 2
• Elderly patients face increased risk of falls, fractures, and cognitive impairment from anticholinergic effects 2

Clinical Pearls and Common Pitfalls

When to Use vs. Avoid

• Second-generation antihistamines are generally preferred over hydroxyzine for daytime use due to reduced sedative effects 2
• Hydroxyzine is most useful when sleep disturbance is a significant problem, not primarily for enhanced antihistamine effect 2
• Despite sedating potential, hydroxyzine is well tolerated in real-world settings with significant improvement in pruritus symptoms and quality of life over 12 weeks 7

Efficacy Considerations

• While more effective than placebo for generalized anxiety disorder, hydroxyzine cannot be recommended as a reliable first-line treatment due to high risk of bias in studies, small sample sizes, and limited high-quality evidence 8, 2
• Hydroxyzine maintains H1-receptor antagonism the following morning with bedtime dosing, though AM/PM dosing regimens may still result in daytime drowsiness due to prolonged half-life 4, 2

Special Clinical Applications

• Adjunctive treatment for opioid-induced pruritus and nausea 2
• Chemical restraint in agitated pediatric patients 2
• Combination therapy with H2 antihistamines and GABA agonists for severe or widespread pruritus 3