Cisapride. Drug interactions of clinical significance

Cisapride is a prokinetic agent which restores motility of the gastrointestinal tract in conditions of decreased bowel transit. It may also alter the absorption of coadministered drugs. The absorption of morphine, diazepam, cyclosporin, alcohol (ethanol) and levodopa are increased. Initial absorption of cimetidine and raniditine is also increased, but overall absorption is lower due to increased bowel transit. The absorption of digoxin, propranolol and the anticoagulants warfarin and phenprocoumon appears unaffected by cisapride, although increase thrombotest values were seen with acenocoumarol (nicoumalone). Drug interactions leading to increased plasma concentrations of cisapride may produce an increase in adverse effects. The most important of these is QT interval prolongation and ventricular arrhythmias. Phenytoin does not appear to affect protein binding of cisapride. Cisapride metabolism is inhibited by the antifungals ketoconazole, fluconazole, itraconazole and miconazole, and by the antibacterials erythromycin, troleandomycin and clarithromycin. Cisapride should not be coadministered with these drugs. Cimetidine produces a small increase in cisapride plasma concentrations, which may be due to inhibition of metabolism. Cisapride absorption is unaffected by other antacids. Atropine may reverse the cisapride-induced increase in peristalsis. Prescribers should remain vigilant to the presence of these and other, as yet unreported, reactions.