Ondansetron and the Risk of Cardiac Arrhythmias: A Systematic Review and Postmarketing Analysis

Study objective: To explore the risk of cardiac arrhythmias associated with ondansetron administration in the context of recent recommendations for identification of high-risk individuals. Methods: We conducted a postmarketing analysis and systematically reviewed the published literature, grey literature, manufacturer's database, Food and Drug Administration Adverse Events Reporting System, and the World Health Organization Individual Safety-Case Reports Database (VigiBase). Eligible cases described a documented (or perceived) arrhythmia within 24 hours of ondansetron administration. The primary outcome was arrhythmia occurrence temporally associated with the administration of a single, oral ondansetron dose. Secondary objectives included identifying all cases associating ondansetron administration (any dose, frequency, or route) to an arrhythmia. Results: Primary: No reports describing an arrhythmia associated with single oral ondansetron dose administration were identified. Secondary: Sixty unique reports were identified. Route of administration was predominantly intravenous (80%). A significant medical history (67%) or concomitant use of a QT-prolonging medication (67%) was identified in 83% of reports. Approximately one third occurred in patients receiving chemotherapeutic agents, many of which are known to prolong the QT interval. An additional third involved administration to prevent postoperative vomiting. Conclusion: Current evidence does not support routine ECG and electrolyte screening before single oral ondansetron dose administration to individuals without known risk factors. Screening should be targeted to high-risk patients and those receiving ondansetron intravenously.