What is the starting dose of hydroxyzine (an antihistamine) for an adult patient with no significant medical history?

Starting Dose of Hydroxyzine for Adults

For an adult patient with no significant medical history, start hydroxyzine at 25 mg three to four times daily for pruritus/allergic conditions, or 50-100 mg four times daily for anxiety, based on FDA-approved dosing. 1

Standard Dosing by Indication

For Pruritus and Allergic Conditions

• Start with 25 mg three to four times daily (TID or QID) for management of pruritus due to chronic urticaria, atopic dermatitis, and other allergic conditions 1
• This represents the FDA-approved starting dose for histamine-mediated pruritus 1

For Anxiety Management

• Start with 50-100 mg four times daily for symptomatic relief of anxiety and tension 1
• Clinical trials have demonstrated efficacy at a fixed dose of 50 mg daily for generalized anxiety disorder 2

Alternative Dosing Strategy: Bedtime Administration

• Consider 10-50 mg at bedtime when adding hydroxyzine to a non-sedating antihistamine regimen 3, 4, 5
• This approach minimizes daytime sedation and psychomotor impairment while maintaining therapeutic benefit 6
• Evening dosing of 50 mg has been shown to maintain histamine receptor antagonism the following morning while mitigating reaction time degradation seen with divided doses 6

Important Clinical Considerations

Sedation and Performance Impairment

• Hydroxyzine causes significant CNS depression with 80% sedation rates, higher than diphenhydramine (50%) or promethazine (60-73%) 5
• Objective testing demonstrates prolonged simple and choice reaction times at doses as low as 25 mg twice daily, without development of tolerance over 5 days 7
• Subjective symptoms do not reliably predict objective performance impairment, meaning patients may not recognize their degree of impairment 7
• Recent forensic data shows hydroxyzine is increasingly identified in impaired driving investigations, with behavioral observations including incoordination, slurred speech, and difficulty following instructions 8

Dose Adjustments for Special Populations

Renal Impairment:

• Reduce dose by half in moderate renal impairment (creatinine clearance 10-20 mL/min) 3, 9, 4
• Avoid entirely in severe renal impairment (creatinine clearance <10 mL/min) 3, 9, 4

Hepatic Impairment:

• Avoid in severe liver disease due to inappropriate sedating effects 3, 9, 4

Elderly Patients:

• Start at the low end of the dosing range and monitor closely for confusion, over-sedation, and fall risk 4, 5
• Hydroxyzine is listed among anticholinergic medications that should be avoided or deprescribed in older adults due to CNS impairment and fall risk 5

Common Pitfalls to Avoid

• Do not use as monotherapy for extended periods due to concerns about reduced concentration and performance 5
• Avoid concomitant use with other CNS depressants, as this enhances performance impairment and sedation 9, 5
• Do not use in early pregnancy - hydroxyzine is specifically contraindicated; if antihistamine therapy is necessary, chlorphenamine is preferred due to its longer safety record 9, 4, 5
• Do not assume tolerance will develop to sedative effects - clinical studies show no development of tolerance to objective or subjective symptoms over 5 days of administration 7

Practical Prescribing Algorithm

1. Determine indication: Pruritus (25 mg TID/QID) vs. Anxiety (50-100 mg QID) 1
2. Assess for contraindications: Early pregnancy, severe renal/hepatic impairment, elderly status 3, 9, 4
3. Consider bedtime dosing strategy (10-50 mg QHS) if daytime sedation is a concern or when combining with non-sedating antihistamines 3, 4, 5, 6
4. Counsel patient extensively about sedation, impaired driving risk, and avoiding alcohol/CNS depressants 8, 7
5. Adjust timing so highest drug levels occur when symptoms are anticipated 4