What are the precautions when prescribing Zofran (ondansetron) to patients with a prolonged QTc interval?

From the Guidelines

Ondansetron (Zofran) should be used with extreme caution or avoided entirely in patients with prolonged QTc intervals due to the risk of further QT prolongation and potentially fatal arrhythmias like Torsades de Pointes. For patients who require antiemetic therapy and have known QTc prolongation, clinicians should first consider alternative antiemetics without QT-prolonging effects, such as prochlorperazine or promethazine. If ondansetron must be used, obtain a baseline ECG before initiating therapy and monitor the QTc interval regularly during treatment, as recommended by the European Society of Cardiology 1. The dose should be reduced to the minimum effective amount, typically not exceeding 8mg per dose, with careful attention to the total daily dose. Avoid administering ondansetron rapidly intravenously; instead, administer over at least 15 minutes. Additionally, be vigilant about drug interactions that could further prolong the QT interval, including other QT-prolonging medications, electrolyte abnormalities (particularly hypokalemia and hypomagnesemia), and concomitant use of CYP3A4 inhibitors that may increase ondansetron levels.

Some key points to consider when prescribing Zofran to patients with a prolonged QTc interval include:

• A 12-lead ECG should be recorded and the QT interval, corrected for heart rate with Bazett’s or Fridericia’s formula, should be obtained in all patients at baseline 1
• Patients with a history of QT prolongation, relevant cardiac disease, treated with QT-prolonging drugs, bradycardia, thyroid dysfunction or electrolyte abnormalities should be monitored by repeated 12-lead ECG 1
• Consider treatment discontinuation or alternative regimens if the QTc is >500 ms, QTc prolongation is >60 ms or dysrhythmias are encountered 1
• Conditions known to provoke torsades de pointes, especially hypokalaemia and extreme bradycardia, should be avoided in patients with drug-induced QT prolongation 1
• Exposure to other QT-prolonging drugs should be minimized in patients treated with potentially QT-prolonging chemotherapy 1

It is also important to note that ondansetron blocks hERG potassium channels in cardiac tissue, which delays cardiac repolarization and prolongs the QT interval, making patients with existing prolongation particularly vulnerable to dangerous cardiac events. Therefore, careful consideration and monitoring are necessary when prescribing ondansetron to patients with prolonged QTc intervals, as recommended by the American College of Cardiology/American Heart Association 1 and the American Heart Association 1.

From the FDA Drug Label

QT Prolongation Inform patients that ondansetron tablets may cause serious cardiac arrhythmias such as QT prolongation. Instruct patients to tell their healthcare provider right away if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode [see Warnings and Precautions (5. 2)].

When prescribing Zofran (ondansetron) to patients with a prolonged QTc interval, precautions should be taken due to the potential risk of QT prolongation. Patients should be instructed to immediately report any signs or symptoms of QT prolongation, such as changes in heart rate, lightheadedness, or syncopal episodes, to their healthcare provider 2.

• Key considerations:
  • Monitor patients with prolonged QTc interval for signs of QT prolongation
  • Instruct patients to report any changes in heart rate or symptoms of QT prolongation
  • Consider alternative treatments or closer monitoring in patients with prolonged QTc interval 2

From the Research

Precautions for Prescribing Zofran (Ondansetron) to Patients with Prolonged QTc Interval

When prescribing Zofran (ondansetron) to patients with a prolonged QTc interval, several precautions should be taken into consideration:

• Patients with a prolonged QTc interval are at increased risk of developing torsades de pointes, a potentially fatal arrhythmia 3, 4, 5, 6.
• Ondansetron has been shown to prolong the QTc interval in patients with cardiovascular disease and additional risk factors for torsades de pointes 5.
• The risk of QTc prolongation is higher in patients with certain risk factors, such as hypokalemia, hypomagnesemia, and a history of thyroid disease or myocardial infarction 7.
• Patients who are taking other QT-prolonging medications or have a history of stroke, hypertension, or diabetes should be closely monitored for QTc prolongation 7.
• Electrocardiogram (ECG) monitoring should be performed before and after administration of ondansetron to patients with a prolonged QTc interval 5, 6.
• Patients who experience QTc prolongation or torsades de pointes after receiving ondansetron should be treated promptly with magnesium and other supportive measures 6.

Risk Factors for Prolonged QTc Interval

Several risk factors have been identified as increasing the risk of prolonged QTc interval, including:

• Age: Older adults are at higher risk of QTc prolongation 7.
• Female sex: Women are at higher risk of QTc prolongation than men 7.
• Hypokalemia: Low potassium levels can increase the risk of QTc prolongation 7.
• Hypomagnesemia: Low magnesium levels can increase the risk of QTc prolongation 6.
• History of thyroid disease or myocardial infarction: Patients with a history of these conditions are at higher risk of QTc prolongation 7.
• Use of QT-prolonging medications: Patients taking other medications that prolong the QTc interval are at higher risk of QTc prolongation 7.