Can a patient with a prolonged QTc (corrected QT) interval receive Zofran (ondansetron)?

From the Guidelines

Ondansetron (Zofran) should be used with caution in patients with prolonged QTc intervals, and alternative antiemetics should be considered when possible. For patients with known QTc prolongation, congenital long QT syndrome, or other significant risk factors for QT prolongation, ondansetron is generally not recommended as it can further extend the QT interval and potentially trigger life-threatening arrhythmias like torsades de pointes 1. If ondansetron must be used in a patient with borderline QT prolongation due to lack of alternatives, it should be administered at the lowest effective dose (typically 4mg rather than 8mg), given slowly if IV, and with ECG monitoring when possible. The risk increases with higher doses, rapid IV administration, electrolyte abnormalities (especially hypokalemia and hypomagnesemia), and concurrent use of other QT-prolonging medications. Some key points to consider when treating patients with QT-prolonging medications include:

• Recording a 12-lead ECG and obtaining the QT interval, corrected for heart rate, at baseline 1
• Monitoring patients with a history of QT prolongation, relevant cardiac disease, or treated with QT-prolonging drugs with repeated 12-lead ECG 1
• Considering treatment discontinuation or alternative regimens if the QTc is ≥500 ms, QTc prolongation is ≥60 ms, or dysrhythmias are encountered 1 Alternative antiemetics that don't significantly affect QT intervals include prochlorperazine, promethazine, metoclopramide (though it has its own cardiac considerations), and dexamethasone. The mechanism behind ondansetron's QT prolongation involves blockade of hERG potassium channels in cardiac cells, which delays ventricular repolarization and extends the QT interval.

From the FDA Drug Label

5.2 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)].

Patients with prolonged QTc interval should be cautious when receiving Zofran (ondansetron).

• The drug label recommends avoiding ondansetron tablets in patients with congenital long QT syndrome.
• However, it does not explicitly state that patients with prolonged QTc interval cannot receive ondansetron.
• ECG monitoring is recommended in patients with conditions that may lead to QT prolongation.
• Given the potential risk of QT prolongation and Torsade de Pointes, it is recommended to exercise caution and consider alternative treatments or close monitoring when administering ondansetron to patients with prolonged QTc interval 2.

From the Research

Patient Considerations for Zofran Administration

• Patients with a prolonged QTc interval may be at increased risk for ventricular arrhythmias, particularly torsades de pointes, when administered Zofran (ondansetron) 3, 4, 5, 6.
• Studies have shown that ondansetron can prolong the QTc interval in patients with cardiovascular disease and additional risk factors for torsades de pointes 5.
• A case study reported a patient who experienced QT prolongation, torsades de pointes, and cardiac arrest after receiving 4 mg of IV ondansetron 6.
• However, another study found that the effect of ondansetron administration on QT prolongation was below the 'significant' value, according to the International Conference on Compliance (ICH) recommendations, and no cases of cardiac arrhythmia were reported 7.

Risk Factors and Monitoring

• Patients with risk factors for torsades de pointes, such as hypokalemia, hypomagnesemia, and heart failure, may be more susceptible to QTc prolongation when administered ondansetron 4, 5, 6.
• Close monitoring of the QTc interval and cardiac function is recommended for patients at high risk for torsades de pointes who receive ondansetron 5.
• The decision to administer Zofran to a patient with a prolonged QTc interval should be made on a case-by-case basis, taking into account the patient's individual risk factors and medical history 3, 4, 5, 6, 7.