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

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Abstract
Aims The objective of this study was to compare the effects of high doses of ebastine with terfenadine and placebo on QTc. Methods Thirty-two subjects were randomly assigned to four treatments (ebastine 60 mg day−1, ebastine 100 mg day−1, terfenadine 360 mg day−1, placebo) 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 ebastine 100 mg was increased by + 10.3 ms which was significantly greater than placebo but was significantly less (P < 0.05) than with terfenadine 360 mg (+ 18.0 ms). There were no statistically significant differences in QTcF between 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 ebastine most likely resulted from overcorrection of the small drug-induced increase in heart rate. Conclusions Ebastine at doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval.