Spontaneous adverse event reports of serious ventricular arrhythmias, QT prolongation, syncope, and sudden death in patients treated with cisapride: An ongoing independent case review (original) (raw)

Gastroenterology, 2000

Abstract

Adverse cardiac events have been reported in patients receiving cisapride. We conducted an independent case review of all spontaneous adverse event reports of serious ventricular arrhythmias (SVAs) and QT prolongation (t QT) and of clinical events possibly due to SVAs in patients treated with the prokinetic agent, classifying cases by confidence in diagnosis (dx) and presence of cofactors. We assigned confidence in dx conservatively (erring on side of dx of LQTS), and decisions were made solely by us, without company involvement. Of 471 cases reported worldwide from December 1990 through March 1999, 327 (69%) cases of LQTS or t QT were identified; in 83 (18%) no LQTS or t QT was identified and in 61 (13%) there were insufficient data to assess LQTS. In most of the 327 LQTS or t QTcases, we had high (122,51% ofLQTS cases) or medium (77, 32%) confidence in LQTS dx; 86 (26%) had only t QT. Recognized cofactors were present in 222 (68%) t QT or LQTS cases. The percentage of LQTS cases with cofactors rose with confidence level (P<.OOI): Recognized cofactors were present in 100 (82%) cases with high confidence LQTS and 54 (70%) with medium confidence, versus 14 (33%) with low confidence. The most common recognized cofactors in t QT or LQTS were coadministration of medications that increase cisapride levels by inhibiting cytochrome P450 3A4 (97 cases, 44%), electrolyte disturbances (69, 31%), and concomitant QT prolonging drugs (54, 24%). Of cases in which cytochrome P450 3A4 inhibitors were coadministered, clarithromycin, erythromycin, or fluconazole, or a combination of these drugs, was administered in 79 (81%). Other medical conditions cited as contraindications in labeling (eg, heart failure) were uncommon sole cofactors (45,14%). Of 34 (14%) LQTS cases without cofactors, 9 (4%) were designated high-confidence. Most patients with high confidence dx LQTS and no cofactors or other labeled conditions had complex medical histories. We conclude that in the vast majority of cases of LQTS in patients receiving cisapride, recognizable and often preventable cofactors are present and that LQTS risk diminishes when this drug is used appropriately. Additional data and analysis from this ongoing study will be presented. GASTROENTEROLOGY Vol. 118, No.4

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