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

Abstract

The cardiac safety of ebastine, a long-acting, non-sedating antihistamine, has been thoroughly assessed in phase I-III clinical studies. Ebastine alone at the recommended doses of 10 mg and 20 mg has no clinically relevant effect on QTc interval in adults and in special patient populations (elderly, children or subjects with hepatic or renal impairment). Ebastine administered 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, respectively) on the QTc interval than terfenadine (18 msec) at three times the recommended dose (360 mg/day). The mean QTc interval prolongation observed with ebastine 100 mg/day was small and not clinically meaningful, although the results were statistically significant vs. placebo. The effect of ebastine 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 systemic exposure for ebastine, which were accompanied by small increases in QTc (approximately 10 msec above ketoconazole or erythromycin alone). Results from individual studies suggest that, when coadministered with ketoconazole, 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 relevant cardiac effects as assessed by serial electrocardiographs and Holter monitoring. The overall cardiac safety profile based on currently available information suggests that ebastine, like loratadine and cetirizine, has a lower potential for causing adverse cardiovascular effects than terfenadine.

Ebastine in allergic rhinitis and chronic idiopathic urticaria

“…Ebastine was not associated with any clinically relevant changes in ECG parameters in these patients, although there was high inter-and intra-subject variability in QTc interval in patients with severe renal impairment (75). In children aged 6-11 years, ebastine syrup 15 mg/day for 6 days was not associated with any adverse ECG effects (75).…”

“…In addition, when QTc was corrected using the Friderica formula, there was no significant difference between either dose of ebastine and placebo, whereas terfenadine caused a significantly greater change in QTc interval than ebastine or placebo (P < 0.0001) (76). No recipients of ebastine experienced an increase in QTc interval of >10% (75).…”

“…On the basis of pooled data from five doubleblind, placebo-controlled clinical trials in adult patients with allergic rhinitis (842 treated with ebastine 1-30 mg/ day; 360 treated with placebo), there were no statistically significant differences in mean QTc interval between ebastine and placebo as assessed by serial ECGs (74). No clinically significant findings were noted over periods of 24 h in 226 patients who underwent Holter monitoring (75). In an open-label study in adult patients treated with ebastine 10 or 20 mg once-daily for 4 months, no patient had a QTc interval prolonged to ‡500 ms or by ‡20% (75).…”

“…Data on the cardiac safety of ebastine are available from studies in healthy volunteers and clinical trials in patients, and show that at therapeutic doses of 10 and 20 mg daily, ebastine has no clinically relevant effect on the QTc interval (75), including in elderly patients (26).…”

“…The ECG effects of ebastine at therapeutic doses (10 and/or 20 mg once-daily) were evaluated in pharmacokinetic studies in elderly volunteers (multiple doses) and in those with renal or hepatic insufficiency (single doses) (75). Ebastine was not associated with any clinically relevant changes in ECG parameters in these patients, although there was high inter-and intra-subject variability in QTc interval in patients with severe renal impairment (75).…”