From the FDA Drug Label
QTc interval prolongation was studied in a double-blind, single-intravenous dose, placebo-and positive-controlled, crossover trial in 58 healthy subjects. The maximum mean (95% upper confidence bound) difference in QTcF from placebo after baseline correction was 19.5 (21.8) milliseconds and 5.6 (7. 4) milliseconds after 15minute intravenous infusions of 32 mg and 8 mg of ondansetron injection, respectively. ECG changes including QT interval prolongation have been seen in patients receiving ondansetron. In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron tablets. Avoid ondansetron tablets in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation [see Clinical Pharmacology (12.2)].
Ondansetron (Zofran) is associated with QT interval prolongation, as evidenced by studies showing a significant exposure-response relationship between ondansetron concentration and ΔΔQTcF. The maximum mean difference in QTcF from placebo after baseline correction was 19.5 milliseconds and 5.6 milliseconds after 15-minute intravenous infusions of 32 mg and 8 mg of ondansetron injection, respectively. Additionally, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron tablets. Therefore, caution is advised when using ondansetron in patients with risk factors for QT prolongation, such as congenital long QT syndrome, electrolyte abnormalities, congestive heart failure, bradyarrhythmias, or those taking other medicinal products that lead to QT prolongation. ECG monitoring is recommended in these patients 1, 1.
From the Research
Relationship between QT Interval Prolongation and Zofran (Ondansetron)
- The relationship between QT interval prolongation and Zofran (ondansetron) has been studied in various research papers 2, 3, 4, 5, 6.
- Studies have shown that ondansetron can cause QT interval prolongation, but the clinical significance of this effect is still being debated 2, 3, 4, 5, 6.
- A study published in 2024 found that the QT prolongation peaked at the fifth minute and remained consistent at the fifteenth and thirty-first minutes after ondansetron administration, with a maximum prolongation of 7.9 ± 18.1 ms 2.
- Another study published in 2011 found that ondansetron administration was associated with a mean QTc increase of 19.3 ± 18 msec in patients with cardiovascular disease and additional risk factors for torsades de pointes 3.
- A study published in 2018 found that ondansetron administration was associated with a mean QTc increase of 16.2 msec in emergency department patients 4.
- A study published in 2024 found that single intravenous dose ondansetron induces QT prolongation in adult emergency department patients, with 8 mg doses associated with higher rates of QTc60 prolongation 5.
- A study published in 2016 found that ondansetron caused a mean prolongation of the QTc by 20 ms, with a mean proportion change from baseline of 5.2% 6.
QT Interval Prolongation and Clinical Significance
- The clinical significance of QT interval prolongation due to ondansetron administration is still being debated 2, 3, 4, 5, 6.
- Some studies have found that the QT prolongation caused by ondansetron is not associated with an increased risk of cardiac arrhythmias 2, 6.
- However, other studies have found that ondansetron may significantly increase the QTc interval in patients with cardiovascular disease and additional risk factors for torsades de pointes 3.
- The FDA has issued a warning that ondansetron may cause QT prolongation, potentially leading to deadly arrhythmias 2.
Risk Factors and Predictive Models
- Certain risk factors, such as cardiovascular disease and additional risk factors for torsades de pointes, may increase the risk of QT interval prolongation due to ondansetron administration 3.
- Predictive models have been developed to forecast QTc60 prolongation post-ondansetron administration, including models that incorporate QT0, QTc0, and ondansetron dosage 5.
- These models may be useful in identifying patients at high risk of QT interval prolongation and in guiding clinical decision-making 5.