Second-generation antihistamines for the treatment of chronic idiopathic urticaria

Chronic idiopathic urticaria (CIU) is a serious disorder that can greatly compromise quality of life. While H1 antihistamines are the accepted first-line treatment for CIU, older generations of these agents (e.g., hydroxyzine, diphenhydramine) are associated with anticholinergic and CNS effects, such as drowsiness and sedation, that can pose risks to patients, especially when driving. Second-generation agents available in the United States (U.S.) (e.g., cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) has greatly reduced these CNS effects, making them the current treatments of choice in CIU, but their potency and tolerability profiles vary. Differences in duration of in vivo receptor occupancy may affect the potency of H1 antihistamines. Levocetirizine appears to have greater in vivo H1 receptor occupancy compared with later generation H1 antihistamines, which may confer an advantageous efficacy/safety profile. This has been confirmed in a recent head-to-head study showing that levocetirizine was more effective than desloratadine in improving pruritus in CIU patients. Fexofenadine has been shown to have a low occupancy of H1 antihistamine receptors in the brain, which reduces the likelihood of sedation. More studies are required to further assess receptor occupancy and other factors that may differentiate the second-generation H1 antihistamines.