What are the indications and dosing guidelines for hydroxyzine in adults, including geriatric patients and those with impaired renal or hepatic function?

Indications for Hydroxyzine

Hydroxyzine is FDA-approved for symptomatic relief of anxiety and tension, management of pruritus (itching) from allergic conditions including urticaria and atopic dermatitis, and as a sedative when used as premedication or following general anesthesia. 1

FDA-Approved Indications

Anxiety Disorders

• Generalized anxiety disorder (GAD): Hydroxyzine at 50 mg/day demonstrates superiority over placebo on all anxiety measures starting from the first week of treatment, with efficacy maintained throughout 4 weeks and comparable efficacy to benzodiazepines 2
• The drug shows particular effectiveness on the cognitive component of anxiety 3
• Important caveat: While effective, hydroxyzine should not be considered a reliable first-line treatment for GAD due to high risk of bias in available studies and small sample sizes 4

Pruritus and Dermatological Conditions

• Urticaria (hives): Hydroxyzine 10-50 mg at bedtime serves as an adjunct to non-sedating antihistamines during the day, particularly helping patients sleep better when itching disrupts rest 5, 6
• Atopic dermatitis and eczema: Used at 10-50 mg at bedtime as a sedating antihistamine to complement daytime non-sedating antihistamines 5
• Not recommended as first-line monotherapy for urticaria due to sedating properties; second-generation non-sedating H1 antihistamines (cetirizine, fexofenadine, loratadine) are preferred 6

Sedation

• Premedication and post-general anesthesia sedation 1
• Nausea and vomiting 7

Off-Label Uses Mentioned in Guidelines

Steroid-Refractory Pruritus

• In immune checkpoint inhibitor toxicity: 10-25 mg four times daily or at bedtime, combined with topical corticosteroids 5

Standard Adult Dosing

For Anxiety

• Standard dose: 50 mg/day in divided doses 2
• Treatment duration: Efficacy demonstrated for up to 3 months 2

For Pruritus

• Standard dose: 10-50 mg at bedtime 5
• Can be dosed as 10 mg every 6 hours as needed for mild symptoms, or 25-50 mg at bedtime for sedation and nighttime symptom control 5
• Duration: 2-4 weeks for mild to moderate itching, then transition to non-sedating antihistamines for long-term management 5

Special Population Dosing

Geriatric Patients

• Start at the low end of the dosing range due to greater frequency of decreased hepatic, renal, or cardiac function 1
• Lower dosages should be considered due to increased risk of sedative effects 5
• High-risk population: Elderly adults are at particularly high risk for side effects from first-generation antihistamines, especially with pre-existing prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment 5
• Sedating drugs may cause confusion and oversedation in the elderly; observe closely 1
• Deprescribing consideration: Hydroxyzine is listed among anticholinergic medications that should be avoided in older adults due to CNS impairment (delirium, slowed comprehension), impaired vision, urinary retention, constipation, sedation, and falls 8

Renal Impairment

• Moderate renal insufficiency (creatinine clearance 10-20 mL/min): Reduce dose by half 5, 6
• The extent of renal excretion has not been fully determined, so care should be taken in dose selection 1

Hepatic Impairment

• Severe hepatic disease: Avoid hydroxyzine entirely due to sedative effects 5, 6
• Elderly patients are more likely to have decreased hepatic function, requiring cautious dosing 1

Critical Safety Warnings

QT Prolongation and Cardiac Risk

• FDA warning: Cases of QT prolongation and Torsade de Pointes reported during post-marketing use 1
• Use with caution in patients with:
  • Risk factors for QT prolongation
  • Congenital long QT syndrome or family history
  • Recent myocardial infarction
  • Uncompensated heart failure
  • Bradyarrhythmias 1
• Avoid concomitant use with other QT-prolonging drugs including Class 1A antiarrhythmics (quinidine, procainamide), Class III antiarrhythmics (amiodarone, sotalol), certain antipsychotics (ziprasidone, quetiapine, chlorpromazine), certain antidepressants (citalopram, fluoxetine), and certain antibiotics (azithromycin, erythromycin, clarithromycin) 1

CNS Depression

• Potentiating action: When used with CNS depressants (narcotics, non-narcotic analgesics, barbiturates), reduce the dosage of concomitant medications 1
• Patients should be warned against driving or operating dangerous machinery 1
• Advise against simultaneous use of other CNS depressant drugs and alcohol 1
• Sedation rates: Hydroxyzine causes 80% sedation rates compared to 50% with diphenhydramine and 60-73% with promethazine 5
• Recent driving impairment data shows hydroxyzine became the most identified antihistamine in DUID investigations in 2023, with observations including incoordination, slurred speech, erratic driving, and crashes 7

Anticholinergic Effects

• Provides better control of rhinorrhea compared to second-generation antihistamines due to anticholinergic properties 5
• However, these same properties cause CNS impairment, impaired vision, urinary retention, and constipation, particularly problematic in older adults 8

Acute Generalized Exanthematous Pustulosis (AGEP)

• Rare but serious skin reaction characterized by fever and numerous small, superficial, sterile pustules 1
• Discontinue at first appearance of skin rash or worsening of pre-existing skin reactions 1
• Do not resume if AGEP suspected; avoid cetirizine or levocetirizine due to cross-sensitivity risk 1

Pregnancy

• Contraindicated in early pregnancy (first trimester) 5, 6
• If antihistamine necessary during pregnancy, chlorphenamine preferred due to long safety record 6

Contraindications and Drug Interactions

Absolute Contraindications

• Early stages of pregnancy 5, 6
• Severe hepatic disease 5, 6
• Concomitant use with tricyclic antidepressants like doxepin due to additive QT prolongation and arrhythmic properties 9

Relative Contraindications Requiring Caution

• Moderate renal impairment (dose adjustment required) 5, 6
• Elderly patients with cognitive impairment, prostatic hypertrophy, or elevated intraocular pressure 5
• Patients on multiple CNS depressants 1

Clinical Pearls and Common Pitfalls

Appropriate Use

• Best role: Nighttime adjunct to non-sedating antihistamines for pruritus, not as monotherapy 5, 6
• Avoid prolonged monotherapy: Not recommended due to concerns about reduced concentration and performance 5
• Transition strategy: After 2-4 weeks for pruritus, transition to non-sedating antihistamines for long-term management 5

Common Pitfalls to Avoid

• Do not use as first-line for urticaria: Second-generation non-sedating antihistamines are preferred 6
• Do not combine with other sedating agents: Particularly avoid combination with doxepin or benzodiazepines due to additive CNS depression and cardiac risks 9
• Do not ignore fall risk in elderly: Hydroxyzine is specifically listed as a medication to deprescribe in older adults due to fall risk 8
• Do not use in delirium management: While other antihistamines are mentioned in delirium guidelines, hydroxyzine's sedating and anticholinergic properties make it inappropriate 8