Pediatric Pharmacovigilance in the Real World: The Ondansetron Case

Stephen B. Freedman, Hospital For Sick Children, Toronto, Canada
Elizabeth Uleryk, Hospital For Sick Children, Toronto, Canada
Maggie Rumantir, Hospital For Sick Children, Toronto, Canada
Yaron Finkelstein, University of Toronto & Hospital For Sick Children, Toronto, Canada (yaron.finkelstein@sickkids.ca)

Background:  Ondansetron hydrochloride is a potent antiemetic.  In 2011, the US Food and Drug Administration (FDA) issued a communication warning that ondansetron may induce fatal arrhythmias. Using post-marketing data we sought 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 post-marketing 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, route) to an arrhythmia.

Results: Primary: No reports describing an arrhythmia associated with single oral ondansetron dose administration were identified.  Secondary: 60 unique reports were identified.  Route of administration was predominantly intravenous (80%). A significant past 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 post-operative vomiting.

Conclusions: Current evidence does not support routine electrocardiogram and electrolyte screening prior to single oral ondansetron dose administration to individuals without known risk factors.  Screening should be targeted to high-risk patients and those administered ondansetron intravenously. Most recent data will be discussed.

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Abstract Reference & Short Personal Biography of Presenting Author

Dr. Yaron Finkelstein is a Professor of Pediatrics, Pharmacology and Toxicology, University of Toronto, a Clinician-Investigator at The Hospital for Sick Children. He serves as a “Thought Leader” for the NIH, and a Chief Medical Officer for NIH's Pediatric Trials Network with Health Canada. He is triple-trained in medical toxicology, clinical pharmacology and paediatric emergency medicine. His research focuses on employing clinical trials, Big Data and translational tools to optimize paediatric therapeutics in acute-care settings and improve the outcomes of accidental and intentional drug overdoses.Dr. Finkelstein’s research was funded by the NIH, CDC, CIHR and Harvard University. He received research awards from The International Society of Pharmcoepidemiology and Drug Safety, The American College of Medical Toxicology, American Academy of Pediatrics and The American Pediatric Association.