What are the alternatives to hydroxyzine (an antihistamine)?

Alternatives to Hydroxyzine for Various Conditions

Second-generation antihistamines are strongly preferred over hydroxyzine (a first-generation antihistamine) due to their significantly lower risk of sedation, performance impairment, and anticholinergic effects. 1

Second-Generation Antihistamines (Preferred Alternatives)

• Cetirizine - Once daily dosing, shortest time to maximum concentration (advantage when rapid effect is needed), may cause mild sedation at higher doses 1
• Loratadine - Once daily dosing, non-sedating, shown to have "antiallergic" effects on mast cell mediator release at higher doses 1
• Desloratadine - Once daily dosing, longest elimination half-life (27 hours), should be discontinued 6 days before skin prick testing 1
• Fexofenadine - Once daily dosing, low occupancy of H1 receptors in the brain, reducing likelihood of sedation 1, 2
• Levocetirizine - Once daily dosing, greater in vivo H1 receptor occupancy compared to other second-generation antihistamines, which may provide better efficacy/safety profile 1, 2
• Mizolastine - Once daily dosing, but contraindicated in cardiac disease, QT prolongation, and when used with drugs that inhibit cytochrome P450 1
• Acrivastine - Requires three times daily dosing due to short half-life 1

Why Second-Generation Antihistamines Are Preferred

• First-generation antihistamines like hydroxyzine cause significant sedation and performance impairment, even when patients deny feeling drowsy 1
• Drivers taking first-generation antihistamines are 1.5 times more likely to be responsible for fatal accidents 1
• Workers taking first-generation antihistamines show impaired performance, reduced productivity, and increased occupational accidents 1
• Hydroxyzine's impaired driving performance worsens with cellular phone use 1
• First-generation antihistamines can cause paradoxical CNS stimulation, particularly in children 1

Special Considerations for Specific Populations

Renal Impairment

• Moderate impairment: Avoid acrivastine; halve doses of cetirizine, levocetirizine, and hydroxyzine 1
• Severe impairment: Avoid cetirizine, levocetirizine, and alimemazine; use loratadine and desloratadine with caution 1

Hepatic Impairment

• Avoid in significant hepatic impairment: Mizolastine, alimemazine, chlorphenamine, and hydroxyzine 1

Pregnancy

• Best to avoid all antihistamines in pregnancy, especially first trimester 1
• Hydroxyzine is specifically contraindicated in early pregnancy 1
• If antihistamine therapy is necessary, chlorphenamine has the longest safety record 1
• Loratadine and cetirizine are FDA Pregnancy Category B drugs (no evidence of harm, but well-controlled human studies are lacking) 1

Other Alternative Approaches for Specific Conditions

For Urticaria

• H2 antihistamines - May provide better control when added to H1 antihistamines 1
• Antileukotrienes (e.g., montelukast) - May benefit aspirin-sensitive patients, but unpredictable response 1
• Short courses of corticosteroids - For urticarial vasculitis and severe delayed pressure urticaria 1

For Anxiety Disorders

• While hydroxyzine has shown efficacy in generalized anxiety disorder compared to placebo, other agents are preferred due to hydroxyzine's side effect profile 3, 4

For Pruritus

• GABA agonists (pregabalin, gabapentin) - For intense, widespread pruritus 1
• Topical corticosteroids - Class I for body (clobetasol propionate, halobetasol propionate, betamethasone dipropionate); Class V/VI for face (aclometasone, desonide, hydrocortisone 2.5%) 1

Common Pitfalls to Avoid

• AM/PM dosing regimen (second-generation in morning, first-generation at night) is not recommended, as first-generation antihistamines have prolonged half-lives and can cause daytime drowsiness and performance impairment even when dosed only at bedtime 1
• Underestimating sedation - Performance impairment can exist without subjective awareness of drowsiness 1
• Drug interactions - Concomitant use of CNS-active substances (alcohol, sedatives, hypnotics, antidepressants) can enhance performance impairment from antihistamines 1