Cardiac effects of ebastine and other antihistamines in humans.
The electrocardiographic effects of ebastine and its active metabolite, carebastine, have been studied alone and in relevant drug-interaction studies in various patient populations. The overall cardiac tolerability of ebastine is excellent. In ebastine dose-ranging studies in adults and children, there were no meaningful dose-related changes in the QTc interval. At high doses of ebastine (5 to 10 times the recommended dose), a modest 10.3 msec increase in QTc was observed. Recommended doses of ebastine had no meaningful effect on QTc in the elderly or in patients with renal or hepatic insufficiency. Interaction studies involving ebastine with ketoconazole revealed a significant increase in the serum ebastine concentration and in the elimination half-life of ebastine, with a modest 18.1 msec increase in QTc (approximately 10 msec above ketoconazole alone) and a plateau QTc-ebastine relationship at higher ebastine levels. Similar, though more minor, QTc findings were observed during coadministration of ebastine with erythromycin. No QTc effects were noted when ebastine was administered with theophylline, and the QTc was similar when ebastine was administered with or without food. These findings indicate that ebastine is well tolerated and, in contrast to terfenadine and astemizole, has no clinically meaningful effect on the QTc interval even at high serum concentrations. As with other 'safe' antihistamines, which have shown similar modest increases in QTc when coadministered with ketoconazole, caution should be exercised when administering ebastine to patients having the long QT syndrome or hypokalaemia, and in patients receiving azole antifungals or macrolide antibacterials.
Moss
A J
AJ
University of Rochester Medical Center, New York, USA.
Morganroth
J
J
D000368:Aged; D002090:Butyrophenones / Q000009:adverse effects* / Q000493:pharmacokinetics; D002648:Child; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006634:Histamine H1 Antagonists / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D010880:Piperidines / Q000009:adverse effects* / Q000493:pharmacokinetics
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; C058249:ebastine