What is the effect of Ondansetron (Zofran) on QT interval?

From the Guidelines

Zofran (ondansetron) can prolong the QT interval, and its use requires caution, especially in patients with pre-existing risk factors, as evidenced by the most recent study 1. When prescribing Zofran, it is essential to consider the potential risk of QT interval prolongation, which can increase the risk of developing dangerous arrhythmias like Torsades de Pointes. The risk factors for QT interval prolongation include:

• Congenital long QT syndrome
• Heart failure
• Electrolyte abnormalities, such as hypokalemia or hypomagnesemia
• Concomitant use of other medications that prolong the QT interval According to the study 1, the QT interval should be evaluated before initiation of treatment and during titration of dose, and strict monitoring for ECG changes is recommended for patients with previous episodes of significant QTc prolongation or torsades de pointes. The use of Zofran should be avoided in patients with a QTc interval greater than 500 milliseconds, and alternative rate-correction formulas, such as Fridericia's formula, should be used to reduce unnecessary interruptions of treatment 1. In addition, the study 1 recommends that patients with drug-induced LQTS should have the offending agent removed, and treatment with the particular drug should be ceased or dose reduced if the QT-interval or QTc reaches a length >500 ms or increases by >60 ms compared with baseline. Overall, the use of Zofran requires careful consideration of the potential risks and benefits, and patients should be closely monitored for signs of QT interval prolongation and arrhythmias. Some key points to consider when prescribing Zofran include:
• Correcting any electrolyte abnormalities before administration
• Considering ECG monitoring in high-risk patients
• Avoiding concomitant use of other medications that prolong the QT interval
• Using alternative rate-correction formulas to reduce unnecessary interruptions of treatment
• Monitoring patients closely for signs of QT interval prolongation and arrhythmias.

From the FDA Drug Label

Cardiac Electrophysiology 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. A significant exposure-response relationship was identified between ondansetron concentration and ΔΔQTcF. Using the established exposure-response relationship, 24 mg infused intravenously over 15 minutes had a mean predicted (95% upper prediction interval) ΔΔQTcF of 14.0 (16. 3) milliseconds. In contrast, 16 mg infused intravenously over 15 minutes using the same model had a mean predicted (95% upper prediction interval) ΔΔQTcF of 9.1 (11.2) milliseconds. In this study, the 8 mg dose infused over 15 minutes did not prolong the QT interval to any clinically relevant extent.

Ondansetron and QT Interval Prolongation: Ondansetron may prolong the QT interval, with the maximum mean difference in QTcF from placebo being 19.5 milliseconds after a 32 mg intravenous infusion and 5.6 milliseconds after an 8 mg intravenous infusion 2. The risk of QT interval prolongation increases with higher doses of ondansetron.

• Key Findings:
  • 32 mg intravenous infusion: 19.5 milliseconds QTcF prolongation
  • 8 mg intravenous infusion: 5.6 milliseconds QTcF prolongation
  • 8 mg dose infused over 15 minutes: no clinically relevant QT interval prolongation
• Clinical Implications: Patients receiving ondansetron, especially at higher doses, should be monitored for QT interval prolongation and associated cardiac risks 2.

From the Research

Zofran and QT Interval Prolongation

• Zofran, also known as ondansetron, is a medication used to prevent nausea and vomiting, and it has been associated with QT interval prolongation 3, 4.
• QT interval prolongation is a condition that can increase the risk of torsades de pointes, a life-threatening arrhythmia 5.
• The risk of QT interval prolongation is higher in patients with certain risk factors, such as hypokalemia, female sex, and advancing age 5.

Studies on Ondansetron and QT Interval Prolongation

• A prospective, observational cohort study found that intravenous ondansetron caused a mean QTc prolongation of 7.9 ± 18.1 ms, which was considered negligible to significant 3.
• Another study found that ondansetron caused a mean prolongation of the QTc by 20 ms, with a mean proportion change from baseline of 5.2% 4.
• Both studies found that the QTc prolongation was not related to the dose of ondansetron, and no serious adverse cardiac electrical events were reported 3, 4.

Monitoring and Prevention

• Close monitoring of electrocardiography (EKG) and electrolytes is necessary to prevent QT interval prolongation and torsades de pointes 5, 6.
• Patients at risk for QT interval prolongation should be educated to go directly to the emergency room if they experience palpitations, lightheadedness, dizziness, or syncope 5.
• The combination of QT-prolonging drugs, such as ondansetron, with other medications that can prolong the QT interval should be avoided 7.