QT-related adverse events with ondansetron and olanzapine: a real-world FAERS analysis with implications for oncology...

QT prolongation remains an important safety concern for antiemetic regimens, especially in oncology where polypharmacy and metabolic stress often intersect. Ondansetron and olanzapine are now used side by side in many chemotherapy and perioperative settings, yet their comparative real-world torsadogenic patterns are not fully understood. We aimed to evaluate the relative frequency of QT-related adverse event reports for both drugs using the FDA Adverse Event Reporting System (FAERS).

We performed a retrospective pharmacovigilance study using OpenVigil 2.1 to extract adult FAERS reports from January 2015 through October 2025. Only primary suspect reports were included. Narrow-term events were defined using two specific MedDRA Preferred Terms: torsades de pointes and electrocardiogram QT prolonged. A broader ventricular arrhythmia set was used for sensitivity analysis. Standard disproportionality statistics (ROR, PRR, chi-square) were calculated, and subgroup analyses examined age, sex, and FAERS serious outcomes.

The analysis included 2,608 ondansetron reports and 15,257 olanzapine reports. Narrow-term QT events were more frequently reported with ondansetron (4.91 percent) than olanzapine (1.61 percent). Ondansetron showed a stronger disproportionality signal with an ROR of 27.24 (95 percent CI 22.78-32.58), compared with olanzapine's ROR of 8.70 (95 percent CI 7.65-9.88). This pattern persisted, although at lower magnitudes, with the broader arrhythmia definitions. Female predominance was observed across both drugs, and most reports came from adults younger than 65 years. Hospitalization and life-threatening events were the most common serious categories.

In real-world reporting, ondansetron demonstrates a descriptively higher QT-related disproportionality signal than olanzapine, a finding that aligns with their known electrophysiologic profiles and prior regulatory experience. Although olanzapine's average QT effect is modest, its signal becomes more visible when clinical conditions amplify vulnerability, which is common in oncology. These results do not establish causality, yet they offer useful context when selecting antiemetic strategies for patients already carrying QT-related risks. Integrating pharmacovigilance patterns with clinical judgment may help clinicians tailor safer antiemetic choices, particularly when multiple QT-active agents are used together.