What are the recommended doses, indications, contraindications, side effects, and precautions for hydroxyzine pamoate in adults and children?

Hydroxyzine Pamoate: Clinical Guide

Primary Indications

Hydroxyzine pamoate is indicated for pruritus associated with allergic conditions and urticaria, and for anxiety management, though it should be used as nighttime adjunctive therapy rather than first-line monotherapy due to significant sedation and performance impairment. 1

Pruritus and Urticaria

• Hydroxyzine is effective for managing pruritus from allergic conditions, urticaria, and dermatological reactions, typically dosed 10-50 mg at bedtime as an adjunct to non-sedating antihistamines during the day. 1, 2
• This combination addresses nighttime symptoms and sleep disturbance while minimizing daytime sedation. 1
• Hydroxyzine should not be used as first-line monotherapy because sedating properties and performance impairment outweigh benefits when used alone. 1

Anxiety

• Hydroxyzine is approved for anxiolytic therapy with dosing of 10-50 mg, though it is not considered first-line treatment due to limited high-quality evidence. 2
• Some evidence suggests hydroxyzine is more effective than placebo for generalized anxiety disorder, but high risk of bias in studies limits strong recommendations. 3

Insomnia

• Mixed efficacy has been demonstrated for sleep onset, maintenance, and quality with hydroxyzine 25-100 mg at bedtime. 4
• May be considered as short-term treatment when previous therapy was ineffective, not tolerated, or contraindicated. 4

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Recommended Dosing

Adults - Standard Dosing

• Pruritus/Urticaria: 10-50 mg at bedtime (most commonly 50 mg) as adjunct to daytime non-sedating antihistamine. 1
• Anxiety: 10-50 mg per dose. 2
• Mild itching: 10 mg every 6 hours as needed for 2-4 weeks. 1
• Bedtime dosing provides sustained effects into the next day due to hydroxyzine's long half-life. 1

Pediatric Dosing

• Atopic dermatitis: 0.7 mg/kg three times daily is as effective as 1.4 mg/kg three times daily but causes significantly less sedation. 5
• Peak serum concentration occurs at approximately 2 hours, with elimination half-life of 7.1 hours in children (increases with age). 5
• Pruritus suppression greater than 85% occurs from 2 to 12 hours after dosing. 5
• Hydroxyzine is approved for anxiolytic therapy in children in both Europe and the United States. 2

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Dose Adjustments in Special Populations

Renal Impairment

• Moderate impairment (CrCl 10-20 mL/min): Reduce dose by 50%. 1
• Severe impairment (CrCl <10 mL/min): Avoid hydroxyzine entirely. 1
• Creatinine clearance should be calculated using CKD-EPI or Cockcroft-Gault equations in elderly patients, as serum creatinine alone overestimates renal function due to reduced muscle mass. 1

Hepatic Impairment

• Severe hepatic disease: Absolute contraindication—hydroxyzine must be avoided due to risk of excessive sedation and potential hepatic encephalopathy. 1, 2

Elderly Patients

• Start at the low end of dosing range (10 mg at bedtime) due to age-related declines in hepatic, renal, and cardiac function. 1
• Elderly adults are at high risk for sedative effects, falls, fractures, anticholinergic effects, and cognitive impairment. 1
• Hydroxyzine produces sedation in approximately 80% of elderly skilled-nursing patients and significantly prolongs reaction times. 1
• Hydroxyzine is specifically listed among medications to deprescribe in older adults due to fall risk. 1
• Sedating antihistamines should not be prescribed for pruritus in elderly patients. 2

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Absolute Contraindications

• Early pregnancy (first trimester): Hydroxyzine is the only antihistamine explicitly contraindicated during early pregnancy. 1, 2
• Severe hepatic disease: Risk of excessive sedation and hepatic encephalopathy. 1
• Severe renal impairment (CrCl <10 mL/min): Absolute contraindication. 1
• Concomitant use with other anxiolytic agents (e.g., benzodiazepines): Contraindicated due to heightened risk of additive CNS depression. 2

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Critical Safety Considerations

Performance Impairment and Driving Risk

• Hydroxyzine causes sedation and performance impairment even when patients deny subjective drowsiness. 1
• Drivers taking hydroxyzine are 1.5 times more likely to be responsible for fatal automobile accidents. 1, 2
• Performance impairment can persist without subjective awareness of drowsiness, and tolerance may not develop. 1
• Impaired driving performance worsens with concurrent activities like cell phone use. 2
• Hydroxyzine impairs learning, work performance, and increases occupational accidents. 1

Sedation Profile

• Hydroxyzine causes 80% sedation rates compared to 50% with diphenhydramine and 60-73% with promethazine. 1
• Multiple daily dosing significantly increases risk of daytime drowsiness, performance impairment, and cognitive effects. 1
• Bedtime dosing mitigates but does not eliminate objective reaction time degradation. 6

Drug Interactions

• Concomitant use with other CNS depressants dramatically enhances performance impairment and sedation. 1
• Avoid combination with other sedative or CNS depressant medications. 1
• Avoid combination with alcohol, which increases drowsiness. 7

Anticholinergic Effects

• Use caution in patients taking other anticholinergic drugs, particularly elderly patients with prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment. 1
• Anticholinergic activity adds to that of other anticholinergic drugs, resulting in CNS impairment, delirium, visual disturbances, urinary retention, constipation, and falls. 1
• Tricyclic antidepressants increase adverse risk when combined with hydroxyzine. 1
• A mandatory medication review for CNS depressants, QT-prolonging agents, and anticholinergic drugs should be performed before initiating hydroxyzine in skilled-nursing residents. 1

Inappropriate Uses

• Hydroxyzine's sedating and anticholinergic properties make it inappropriate for delirium management. 1
• Prolonged use as monotherapy is not recommended due to concerns about reduced concentration and performance. 1, 2

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Practical Treatment Algorithm for Pruritus/Urticaria

Step 1: Initial Management

• Begin with a non-sedating second-generation H1-antihistamine (e.g., loratadine 10 mg or cetirizine 10 mg) once daily in the morning. 1
• Offer patients a choice of at least two different non-sedating antihistamines, as individual responses vary. 1

Step 2: Escalation for Inadequate Response (2-4 weeks)

• Increase the dose of the non-sedating antihistamine up to four-fold (e.g., cetirizine up to 40 mg daily) before considering addition of a sedating agent. 1, 7

Step 3: Adding Hydroxyzine for Persistent Nighttime Symptoms

• If nighttime itching and sleep disturbance persist despite optimized non-sedating antihistamine dosing, add hydroxyzine 10-50 mg at bedtime. 1
• Adjust hydroxyzine dose according to tolerability and renal function, halving the dose in moderate renal impairment and starting at 10 mg in elderly patients. 1
• This adjunct does not improve overall urticaria control compared with higher-dose non-sedating antihistamines alone, but may aid sleep. 1

Step 4: Transition for Long-Term Management

• Transition to non-sedating antihistamines for long-term management; avoid hydroxyzine as prolonged monotherapy. 1

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Common Pitfalls to Avoid

• Do not use AM/PM split dosing of hydroxyzine and non-sedating antihistamines as a cost-saving strategy—hydroxyzine's long half-life causes significant daytime impairment even with bedtime-only dosing. 1
• Do not assume patients are unimpaired if they deny drowsiness—performance impairment persists without subjective awareness. 1
• Do not prescribe hydroxyzine to patients requiring optimal cognitive function (e.g., drivers, operators of heavy machinery, students). 1
• Do not combine with other anticholinergic agents in elderly patients without considering alternative anxiolytic options such as SSRIs. 1
• The combination of loratadine and hydroxyzine is most useful when sleep disturbance is a significant problem, not primarily for enhanced antihistamine effect. 2

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Side Effects

Common

• Sedation/drowsiness (most common adverse effect). 5, 6
• Dry mouth. 6, 4
• Irritability. 6

Less Common

• Blurred vision. 7
• Rapid heartbeat. 7

Serious Concerns in Elderly

• Falls and fractures. 1, 2
• Cognitive impairment and delirium. 1
• Urinary retention. 1
• Constipation. 1

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Comparative Efficacy

• Hydroxyzine is equivalent to benzodiazepines (chlordiazepoxide) and buspirone in terms of efficacy, acceptability, and tolerability for anxiety, but associated with higher rate of sleepiness/drowsiness. 3
• Hydroxyzine 50 mg at bedtime maintains skin H1-receptor antagonism the following morning comparable to terfenadine 60 mg twice daily, with universal wheal suppression. 6
• Hydroxyzine 25 mg preserves memory and attention in elderly subjects better than lorazepam 1 mg, which causes clear deficiencies in memory recall. 8