What are the considerations for using Ondansetron (generic name) in a patient with cardiac disease?

From the Guidelines

Ondansetron should be used with caution in cardiac patients due to its potential to cause QT interval prolongation, and the lowest effective dose should be administered with ECG monitoring when possible. The standard adult dose is 4-8 mg orally or intravenously every 8-12 hours as needed for nausea and vomiting. In cardiac patients, particularly those with known QT interval prolongation, heart failure, or electrolyte abnormalities, ondansetron should be used at the lowest effective dose and with ECG monitoring when possible, as recommended by the FDA after reviewing the cardiac safety concerns associated with its use 1.

The medication can cause QT interval prolongation, which may increase the risk of developing torsades de pointes, a potentially life-threatening arrhythmia. This risk is dose-dependent and more significant with IV administration, especially with rapid infusion. Before administering ondansetron to cardiac patients, check for drug interactions with other QT-prolonging medications and ensure potassium and magnesium levels are normal. Alternative antiemetics like prochlorperazine or metoclopramide may be considered for patients at high risk of cardiac complications, though these agents have their own side effect profiles.

Some studies have compared ondansetron with other 5-HT3 antagonists, such as palonosetron, and found that palonosetron is superior in preventing delayed nausea and vomiting 1. However, the primary concern in cardiac patients is the potential for QT interval prolongation, and ondansetron's safety profile in this regard should be carefully considered. The benefit of controlling nausea and vomiting must be weighed against the potential cardiac risks in each individual patient.

Key considerations when using ondansetron in cardiac patients include:

• Using the lowest effective dose
• Monitoring ECG when possible
• Checking for drug interactions with other QT-prolonging medications
• Ensuring potassium and magnesium levels are normal
• Considering alternative antiemetics for patients at high risk of cardiac complications.

From the FDA Drug Label

QT Prolongation Inform patients that ondansetron tablets may cause serious cardiac arrhythmias such as QT prolongation. Ondansetron Injection should be avoided in these patients, since they may be more at risk for cardiac arrhythmias such as QT prolongation and Torsade de Pointes.

• Cardiac Risk: Ondansetron may cause serious cardiac arrhythmias, including QT prolongation.
• Precautions: Patients with a personal or family history of abnormal heart rhythms, hypokalemia, or hypomagnesemia should be cautious when taking ondansetron.
• Monitoring: Patients should be instructed 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 2 3. The use of ondansetron in cardiac patients should be done with caution, as it may cause QT prolongation and other cardiac arrhythmias.

From the Research

Ondansetron and Cardiac Safety

• Ondansetron is a 5-HT₃ receptor antagonist commonly used as an antiemetic to prevent nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively 4.
• The US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes 4.

QT Interval Prolongation

• Studies have shown that ondansetron can cause QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades 5, 6, 7.
• The mean QTc interval prolongation after ondansetron administration was found to be around 16-20 ms in several studies 5, 6, 7.
• A study found that 31% and 46% of patients with heart failure and acute coronary syndromes, respectively, met gender-related thresholds for a prolonged QTc interval after ondansetron exposure 5.

Clinical Significance

• While QTc prolongation does occur in adult patients receiving IV ondansetron, the clinical impact is questionable 6.
• None of the patients in several studies had an ondansetron-related cardiac adverse event 6, 7.
• However, patients who are at high risk for torsades de pointes and receiving ondansetron should be followed via telemetry when admitted to hospital 5.

Comparison with Other Antiemetics

• A study found that droperidol and ondansetron induced similar clinically relevant QTc interval prolongations when used in treatment of postoperative nausea and vomiting 8.
• The safety of 5-hydroxytryptamine type 3 antagonists, such as ondansetron, may not be superior to that of low-dose droperidol in this context 8.