What is the relationship between QT interval (QT) prolongation and Zofran (ondansetron)?

From the Guidelines

Zofran (ondansetron) is known to prolong the QT interval, which can increase the risk of cardiac arrhythmias, particularly torsades de pointes.

Relationship between QT interval prolongation and Zofran (ondansetron)

• The evidence suggests that ondansetron can prolong the QT interval, and this effect is more pronounced in certain conditions, such as hypokalemia or when used in combination with other drugs that also prolong the QT interval 1.
• A list of QT-interval-prolonging medications, including ondansetron, has been compiled, highlighting the potential risk of QT prolongation and dysrhythmia associated with its use 1.
• The British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) also mention QTc prolongation as a common cardiovascular side effect, particularly when ondansetron is used in combination with other drugs that prolong the QT interval 1.
• The European LeukemiaNet expert panel recommends avoiding the concomitant use of drugs like ondansetron that are known to prolong the QTc interval, and modifying QT monitoring in accordance with recent studies 1.
• It is essential to monitor patients who receive ondansetron, especially those with previous episodes of significant QTc prolongation or torsades de pointes, or those with other risk factors for cardiac arrhythmias, and to adjust the treatment accordingly 1.

From the FDA Drug Label

1. 2 QT Prolongation Electrocardiogram (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)].

QT interval prolongation is a potential risk associated with the use of Zofran (ondansetron). The FDA drug label recommends avoiding the use of ondansetron in patients with congenital long QT syndrome and ECG monitoring in patients with certain risk factors, such as electrolyte abnormalities or congestive heart failure 2.

From the Research

QT Interval Prolongation and Zofran (Ondansetron)

• The relationship between QT interval prolongation and Zofran (ondansetron) has been studied in several research papers 3, 4, 5, 6, 7.
• 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% 3.
• Another study published in 2024 found that the QT prolongation associated with ondansetron use in the emergency department was above the 'negligible' but below the 'significant' value, according to the International Conference on Compliance (ICH) recommendations 4.
• A prospective observational study published in 2024 found that single intravenous dose ondansetron induces QT prolongation in adult emergency department patients, and that the predictive models for QTc prolongation 1-hour post-ondansetron administration showed a significant association with baseline QT and QTc intervals, as well as ondansetron dosage 5.
• A thorough QTc study published in 2014 found that single intravenous doses of ondansetron greater than 16 mg should no longer be used, due to the risk of QT interval prolongation 6.
• A review of the cardiac safety of ondansetron published in 2013 found that the dose of ondansetron that the FDA has concerns about is 32 mg i.v., and that more research needs to be undertaken on the relationship between QT prolongation and torsades in order to produce clear-cut evidence of proarrhythmic risk 7.

Key Findings

• Ondansetron has been shown to cause QT interval prolongation in several studies 3, 4, 5, 6.
• The risk of QT interval prolongation associated with ondansetron use is dose-dependent, with higher doses associated with a greater risk of prolongation 6.
• The clinical significance of QT interval prolongation associated with ondansetron use is unclear, and more research is needed to fully understand the relationship between QT prolongation and torsades 7.
• Baseline QT and QTc intervals, as well as ondansetron dosage, have been shown to be predictive of QTc prolongation 1-hour post-ondansetron administration 5.