What are the uses and dosages of Hydroxyzine (antihistamine)?

Hydroxyzine: Clinical Uses and Dosing

Hydroxyzine is a first-generation antihistamine with established efficacy for pruritus management (particularly at bedtime) and generalized anxiety disorder, with FDA-approved dosing of 25 mg TID-QID for pruritus and 50-100 mg QID for anxiety in adults. 1

Primary Clinical Indications

Pruritus Management

• Hydroxyzine is most appropriately used as a nighttime adjunct (10-50 mg at bedtime) for patients with pruritus, complementing non-sedating antihistamines during the day 2, 3
• For allergic conditions including chronic urticaria, atopic dermatitis, and contact dermatoses, the FDA-approved dosing is 25 mg TID or QID in adults 1
• For steroid-refractory pruritus (including immune checkpoint inhibitor-related), dosing of 10-25 mg QID or at bedtime can be combined with topical corticosteroids 2
• Hydroxyzine relieves pruritus through H1-receptor blockade and provides sedative properties beneficial for nighttime itching 3
• The British Association of Dermatologists found hydroxyzine significantly improves symptoms and quality of life when used as nighttime medication alongside daytime non-sedating antihistamines 3

Anxiety Disorders

• For generalized anxiety disorder and psychoneurosis-related anxiety, FDA-approved dosing is 50-100 mg QID 1
• Clinical trials demonstrate superiority over placebo from the first week of treatment, with efficacy maintained throughout 4 weeks and no rebound anxiety after abrupt discontinuation 4, 5
• Hydroxyzine shows equivalent efficacy to benzodiazepines and buspirone but with greater cognitive improvement compared to lorazepam 2, 4

Opioid-Induced Pruritus

• Hydroxyzine (oral or intramuscular) is recommended by the National Comprehensive Cancer Network for managing opioid-induced pruritus in cancer patients 6

Dosing by Indication

Standard Adult Dosing

• Pruritus: 25 mg TID-QID (FDA-approved) 1 or 10-50 mg at bedtime (guideline-recommended) 2, 3
• Anxiety: 50-100 mg QID 1
• Preoperative sedation: 50-100 mg 1
• Mild symptoms: 10 mg every 6 hours as needed 2

Pediatric Dosing

• Under 6 years: 50 mg daily in divided doses 1
• Over 6 years: 50-100 mg daily in divided doses 1
• Preoperative: 0.6 mg/kg body weight 1

Special Population Adjustments

Renal Impairment

• For moderate renal insufficiency (creatinine clearance 10-20 mL/min), reduce dose by half 2, 3

Hepatic Impairment

• Avoid hydroxyzine in severe hepatic disease due to inappropriate sedative effects 2, 3

Elderly Patients

• Use lower dosages due to increased risk of sedative and anticholinergic effects 2
• Older adults are at high risk for side effects, particularly with pre-existing prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment 2
• The American Geriatrics Society recommends avoiding hydroxyzine in elderly patients with cognitive impairment 3

Pregnancy

• Hydroxyzine is contraindicated in early pregnancy 2, 3

Treatment Duration and Strategy

Short-Term Use Preferred

• Extended monotherapy is not recommended; hydroxyzine should be used as a nighttime adjunct to non-sedating antihistamines 2
• For mild to moderate itching, typical duration is 2-4 weeks 2
• Transition to non-sedating antihistamines for long-term management 2

Dosing Schedule Optimization

• Bedtime dosing (50 mg qhs) mitigates psychomotor performance degradation while maintaining H1-receptor antagonism the following morning 7
• Evening dosing strategy minimizes reaction time impairment compared to divided doses 7

Critical Safety Considerations

Sedation and Performance Impairment

• Hydroxyzine causes 80% sedation rates (compared to 50% with diphenhydramine and 60-73% with promethazine) 2
• Significantly prolongs simple and choice reaction times without developing tolerance over 5 days 8
• Avoid concomitant use with other CNS depressants, as this enhances performance impairment and sedation 2
• The FDA has issued a black box warning about combining opioids with sedating medications like hydroxyzine 6

Common Side Effects

• Sleepiness/drowsiness (28% vs 14% placebo), typically transient and appearing during the first week 5
• Dry mouth (14% vs 5% placebo) 5
• Weight gain (12% vs 10% placebo) 5
• Loss of concentration (9% vs 8% placebo) 5

Anticholinergic Effects

• Anticholinergic properties provide better control of rhinorrhea compared to second-generation antihistamines 2
• However, these effects increase risk in patients with prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment 2

Clinical Pitfalls to Avoid

• Do not rely on subjective symptoms as predictors of objective performance impairment—patients may have significant reaction time prolongation without reporting drowsiness 8
• Do not use prolonged monotherapy for pruritus—combine with non-sedating antihistamines and transition for long-term management 2
• Do not prescribe in severe liver disease, early pregnancy, or elderly patients with cognitive impairment 2, 3
• Do not combine with other CNS depressants without careful consideration of enhanced sedation risk 6, 2