CISAPRIDE - DRUG-INTERACTIONS OF CLINICAL-SIGNIFICANCE

Cisapride is a prokinetic agent which restores motility of the gastroi ntestinal tract in conditions of decreased bowel transit, It may also alter the absorption of coadministered drugs. The absorption of morphi ne, diazepam, cyclosporin, alcohol (ethanol) and levodopa are increase d, Initial absorption of cimetidine and raniditine is also increased, but overall absorption is lower due to increased bowel transit, The ab sorption of digoxin, propranolol and the anticoagulants warfarin and p henprocoumon appears unaffected by cisapride, although increase thromb otest values were seen with acenocoumarol (nicoumalone). Drug interact ions leading to increased plasma concentrations of cisapride may produ ce an increase in adverse effects, The most important of these is QT i nterval prolongation and ventricular arrhythmias. Phenytoin does not a ppear to affect protein binding of cisapride, Cisapride metabolism is inhibited by the antifungals ketoconazole, fluconazole, itraconazole a nd 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 concen trations, which may be due to inhibition of metabolism. Cisapride abso rption is unaffected by other antacids. Atropine may reverse the cisap ride-induced increase in peristalsis. Prescribers should remain vigila nt to the presence of these and other, as yet unreported, reactions.