What is the impact of Zofran (ondansetron) on the QT interval?

From the Guidelines

Zofran (ondansetron) can prolong the QT interval, as listed in the table of QT-Interval-Prolonging Medications in Pediatrics 1. This effect is particularly concerning in patients with pre-existing QT prolongation, those taking other QT-prolonging medications, or those with electrolyte abnormalities (particularly hypokalemia or hypomagnesemia). The mechanism behind this QT prolongation is the blockage of hERG potassium channels in cardiac cells by ondansetron, leading to delayed cardiac repolarization. Key points to consider include:

• The risk of QT prolongation is dose-dependent, with higher doses (especially above 16 mg given intravenously) posing a greater risk.
• Patients at increased risk should be considered for ECG monitoring.
• Healthcare providers should avoid exceeding recommended doses and correct any electrolyte abnormalities before administering ondansetron.
• The risk is generally lower with oral administration and standard antiemetic dosing (4-8 mg).
• Alternative antiemetics may be considered for patients with significant cardiac risk factors, as the potential for QT prolongation can lead to dangerous ventricular arrhythmias like torsades de pointes, although this is rare with typical therapeutic doses 1.

From the FDA Drug Label

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. 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 15-minute intravenous infusions of 32 mg and 8 mg of ondansetron injection, respectively.

Zofran (ondansetron) can cause QT interval prolongation, as evidenced by ECG changes in patients receiving the drug. The degree of QTc interval prolongation varies depending on the dose, with a maximum mean difference of 19.5 milliseconds observed after a 32 mg intravenous infusion.

• Key points:
  • QT interval prolongation is a potential risk associated with ondansetron use.
  • The risk of QT interval prolongation increases with higher doses of ondansetron.
  • Patients with congenital long QT syndrome should avoid ondansetron.
  • ECG monitoring is recommended in patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias, or those taking other medicinal products that lead to QT prolongation 2.

From the Research

Zofran Impact on QT Interval

• The impact of Zofran (ondansetron) on the QT interval has been studied in various research papers 3, 4, 5, 6, 7.
• Prolongation of the QT interval has been observed with ondansetron and other members of the 5-HT3 antagonist class 3.
• A thorough QTc study of ondansetron conducted in accordance with ICH E14 guidelines found that single intravenous (IV) doses of ondansetron greater than 16 mg should no longer be used due to the risk of QT interval prolongation 3.
• The study also found that the maximum mean difference in QTcF, compared to placebo and corrected for baseline, was less than 10 milliseconds (ms) after an 8 mg IV dose and approximately 20 ms after the 32 mg dose 3.

QT Interval Prolongation Risk Factors

• Patients with cardiovascular disease and additional risk factors for torsades de pointes are at higher risk of QT interval prolongation due to ondansetron administration 6.
• A prospective observational study found that 8 mg doses of ondansetron were associated with higher rates of QTc60 prolongation, while 4 mg doses favored maintaining QTc60 within normal limits 4.
• The study also found that a QTc0 of 400 msec had a sensitivity of 100% in predicting a QTc60 < 480 msec, while a QTc0 > 460 msec predicted a QTc60 > 480 msec with a specificity of 98% 4.

Clinical Implications

• Anesthesia providers and perioperative nurses must be informed regarding the importance of the QT interval and the risk of QT prolongation due to ondansetron administration 5.
• Patients who are at high risk for torsades de pointes and receiving ondansetron should be followed via telemetry when admitted to hospital 6.
• Routine ECG monitoring in patients given ondansetron due to the risk of QTc prolongation may not be cost-effective in the absence of a known risk of cardiac arrhythmia 7.