A review of the cardiac systemic side-effects of antihistamines: ebastine

The cardiac safety of ebastine, a long-acting, non-sedating antihistamine, has been thoroughly assessed in phase T-m clinical studies. Ebastine alone at the recommended doses of 10 mg and 20 mg has no clinically relevant effe ct on QTc interval in adults and in special patient populations (elderly, c hildren or subjects with hepatic or renal impairment). Ebastine administere d at 60 and 100 mg/day (3-5 times the maximum recommended dose) for 1 week had statistically significantly smaller effects (3.7 and 10.3 msec, respect ively) on the QTc interval than terfenadine (18 msec) at three times the re commended dose (360 mg/day), The mean QTc interval prolongation observed wi th ebastine 100 mg/day was small and not clinically meaningful, although th e results were statistically significant vs, placebo. The effect of ebastin e 60 mg/day was not statistically different from placebo. Steady-state drug interaction studies demonstrated that the co-administration of ebastine 20 mg with ketoconazole or erythromycin produced significant increases in sys temic exposure for ebastine, which were accompanied by small increases in Q Tc (approximately 10 msec above ketoconazole or erythromycin alone). Result s from individual studies suggest that, when coadministered with ketoconazo le, ebastine produces similar changes in QTc interval measurements compared to loratadine and cetirizine. Pooled data from clinical efficacy trials of ebastine 1-30 mg/day administered for 2-3 weeks showed no clinically relev ant cardiac effects as assessed by serial electrocardiographs and Holter mo nitoring. The overall cardiac safety profile based on currently available i nformation suggests that ebastine, like loratadine and cetirizine, has a lo wer potential for causing adverse cardiovascular effects than terfenadine.