The macrolides are generally well tolerated when used for the treatment of acute infections. Even when given long term for prophylaxis, there are few discontinuations due to side-effects. There are isolated reports of QT(c) prolongation in patients treated with erythromycin and other 14-membered-ring macrolides. Since the 14-membered-ring macrolides are metabolized by P450 isoenzymes, there is the potential for interaction with other therapeutic agents also metabolized in this way. Pharmacokinetic studies have demonstrated interactions between either erythromycin or clarithromycin and cyclosporin, cisapride, pimozide, disopyramide, astemizole, carbamazepine, midazolam, digoxin, hydroxymethylglutaryl-coenzyme A reductase inhibitors (i.e. 'statins') and warfarin. In patients receiving such concurrent therapy, azithromycin may be superior to erythromycin and clarithromycin.