Contraindicated Use of Cisapride

TLDR

Cisapride, a gastrointestinal promotility agent introduced in 1993, rapidly gained widespread use but was linked to serious cardiac arrhythmias, leading the FDA to issue a black‑box warning in 1995 and yet its prescriptions continued to rise. Clinical studies revealed that cisapride prolongs the QT interval and induces torsade de pointes, particularly when co‑administered with CYP3A4 inhibitors that impair its metabolism.

Abstract

ISAPRIDE IS A GASTROINTESTInal tract promotility agent that was first marketed in the United States in August 1993 with a label indication for nocturnal heartburn. 1Use grew rapidly so that in 1995 there were approximately 5 million outpatient cisapride prescriptions filled in the United States. 2 However, by this time, the Food and Drug Administration (FDA) had received 34 cases of torsade de pointes and 23 of prolonged QT interval in cisapride users, including 4 deaths. 3ince many of these cases were in patients taking drugs that inhibited the cytochrome P450-3A4 enzymes that metabolize cisapride, 1 a "blackbox" warning was added to the cisapride label in 1995 contraindicating use in patients taking drugs that affected cisapride metabolism and the manufacturer sent a "Dear Health Care Professional" letter.In April 1996, more information on the cases was published. 3The second report also suggested that use of cisapride could be hazardous in patients taking medications that prolonged the QT interval or with chronic diseases that predisposed to cardiac arrhythmias.Despite the black-box warning, use of cisapride continued to increase in the United States so that in 1998 there were 7 million prescriptions dispensed. 2Further information accumulated on the potential adverse effects of cisapride.Clinical studies demonstrated that