AbstractBackgroundChronic idiopathic urticaria (CIU) is a common dermatological condition. Its pathogenesis involves mainly histamine and also other mediators, including platelet‐activating factor (PAF) and tumor necrosis factor‐α (TNF‐α). In the absence of an exact etiology, H1‐antihistaminics are the mainstay of treatment. Levocetirizine is widely prescribed forCIU. Rupatadine, a newer antihistaminic, hasPAFreceptor antagonist activity and has shown anti‐TNF‐α activityin vitro. These additional anti‐inflammatory effects may improve its efficacy.ObjectivesThis study was conducted to compare the efficacy and safety of rupatadine and levocetirizine, respectively, inCIUpatients.MethodsA prospective, open, comparative, randomized study was conducted in 100 patients, of whom 50 were treated with levocetirizine and 50 were treated with rupatadine. Efficacy parameters used were urticarial activity score (UAS) and Dermatology Life Quality Index (DLQI) values. Safety was evaluated by monitoring for adverse drug reactions and by using the critical flicker fusion threshold (CFFT) test and a visual analog scale (VAS) at baseline, and at 2, 4, and 6 weeks.ResultsThe meanUASdecreased to 0.10 in the levocetirizine group and to 0.38 in the rupatadine group. Patients in the levocetirizine group showed a more significant (P < 0.001) improvement, although symptoms improved in both groups. Significant reductions in meanDLQIscores were observed in both groups, but the decrease was statistically significant in the levocetirizine group (P < 0.05). Somnolence was the most common side effect in both groups. Patients in the levocetirizine group showed more psychomotor impairment based on theCFFTtest. Findings on theVASshowed sedative effects in both groups (P < 0.05).ConclusionsLevocetirizine was found to be more efficacious than rupatadine inCIUpatients, but both drugs caused mild sedation.