Effects of supratherapeutic doses of ebastine and terfenadine on the QT interval

Aims The objective of this study was to compare the effects of high doses o f ebastine with terfenadine and placebo on QTc. Methods Thirty-two subjects were randomly assigned to four treatments (ebas tine 60 mg day(-1), ebastine 100 mg day(-1), terfenadine 360 mg day(-1), pl acebo) administered for 7 days. Serial ECGs were performed at baseline and day 7 of each period. QT interval was analysed using both Bazett (QTcB) and Fridericia (QTcF) corrections. Results Ebastine 60 mg (+ 3.7 ms) did not cause a statistically significant change in QTcB compared with placebo (+ 1.4 ms). The mean QTcB for ebastin e 100 mg was increased by + 10.3 ms which was significantly greater than pl acebo but was significantly less (P < 0.05) than with terfenadine 360 mg ( 18.0 ms). There were no statistically significant differences in QTcF betw een ebastine 60 mg (-3.2 ms) or ebastine 100 mg (1.5 ms) and placebo (-2.1 ms); although terfenadine caused a 14.1 ms increase which was significantly different from the other three treatments. The increase in QTcB with ebast ine most likely resulted from overcorrection of the small drug-induced incr ease in heart rate. Conclusions Ebastine at doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval.