In combination with 1st-generation antihistamines, quinidine-like effects on the cardiac conducting tissues and clinically significant interactions have raised the question of the drug safety. This prodysrhythmic effect has also been briefly mentioned in comparisons of nonsedative H1 antihistamines. In combination with drugs used to treat arrhythmias, ebastine may increase the risk of tachycardia. Large doses of alcohol may cause cardiac and respiratory depression. In combination with macrolides (eg, erythromycin and clarithromycin that induce cytochrome P-450) that is responsible for the biotransformation of antihistamine to its active metabolite, an increase in the antihistaminic effect may be seen.