Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and food and drug administration regulatory actions

• Published in: The American journal of gastroenterology Vol. 96; no. 6; pp. 1698 - 1703
• Main Authors: WYSOWSKI, Diane K, CORKEN, Ann, GALLO-TORRES, Hugo, TALARICO, Lilia, RODRIGUEZ, Evelyn M
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing 01.06.2001; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adverse Drug Reaction Reporting Systems; Arrhythmias, Cardiac - chemically induced; Biological and medical sciences; Cisapride - adverse effects; Contraindications; Drug and Narcotic Control; Electrocardiography. Vectocardiography; Electrodiagnosis. Electric activity recording; Female; Gastroenterology; Gastrointestinal Agents - adverse effects; Humans; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Product Surveillance, Postmarketing; Risk Factors; Tachycardia, Ventricular - chemically induced; Time Factors; Torsades de Pointes - chemically induced; United States; United States Food and Drug Administration; Ventricular Fibrillation - chemically induced; Human; Cisapride; Wave burst; Arrhythmia; Report; Prolonged QT interval; Cardiovascular disease; Pharmacovigilance; Excitability disorder; Electrodiagnosis; Chemotherapy; Association; Etiology; Heart disease; Risk factor; Secondary effect; Electrocardiography; Benzamide derivatives; Antiemetic; Food and Drug Administration
• ISSN: 0002-9270; 1572-0241
• DOI: 10.1111/j.1572-0241.2001.03927.x

To describe the postmarketing safety data used in the risk assessment of cisapride and to summarize the regulatory actions of the Food and Drug Administration (FDA). The FDA analyzed reports of patients who developed QT prolongation, torsades de pointes, and ventricular arrhythmia in association with the use of cisapride to assess probable etiology and risk factors. While cisapride was being marketed from 1993-1999, the FDA received reports of the following patients: 117 who developed QT prolongation; 107, torsades de pointes; 16, polymorphic ventricular tachycardia; 18, ventricular fibrillation; 27, ventricular tachycardia; 25, cardiac arrest; 16, serious (unspecified) arrhythmia; and 15, sudden death; for a total of 341 individual patients affected, following use of cisapride. Eighty (23%) of the 341 patients died. Deaths were directly or indirectly associated with an arrhythmic event. Factors that suggested an association with cisapride included a temporal relationship between use of cisapride and arrhythmia, the absence of identified risk factors and other explanations for arrhythmia in some patients, and cases of positive dechallenge and rechallenge. In most individuals, the arrhythmia occurred in the presence of risk factors (other drugs and/or medical conditions). Postmarketing reports and pharmacokinetic and electrophysiological data provided evidence that cisapride is associated with the occurrence of QT prolongation and torsades de pointes. The risk of fatal arrhythmia with cisapride was believed to outweigh the benefit for the approved indication, treatment of nocturnal heartburn due to gastroesophageal reflux disease, leading to the drug's discontinuation in the United States.