Is 8 mg of Zofran (ondansetron) safe in a patient with a prolonged QT interval (QTc) of 480 ms?

From the Guidelines

I would not recommend taking 8 mg of Zofran (ondansetron) with a QTc interval of 480 milliseconds due to safety concerns. Zofran can prolong the QTc interval, and your current QTc of 480 ms is already at the upper limit of normal (generally considered 450 ms for men and 470 ms for women) 1. Taking Zofran could further increase your QTc interval, potentially putting you at risk for dangerous heart rhythm disturbances like Torsades de Pointes. This risk is dose-dependent, meaning higher doses pose greater risk. Some key points to consider:

• The QT interval should be evaluated before initiation of treatment and during titration of dose 1
• Concomitant treatment with more than one drug with the propensity of prolonging the QT interval should be avoided if possible 1
• If the QT-interval or QTc reaches a length >500 ms or increases by >60 ms compared with baseline, treatment with the particular drug should be ceased or dose reduced 1 Instead, discuss alternative anti-nausea medications with your healthcare provider that don't affect QTc, such as promethazine, prochlorperazine, or metoclopramide. If you're experiencing nausea and vomiting, it's essential to address it, but safely given your cardiac status. Your doctor might also want to investigate the cause of your prolonged QTc and check for other factors that could be contributing, such as electrolyte abnormalities or other medications. Some medications that can prolong the QT interval include:
• Antiemetics like ondansetron and dolasetron 1
• Antipsychotics 1
• Macrolides like azithromycin, clarithromycin, and erythromycin 1
• Fluoroquinolones like ciprofloxacin, levofloxacin, and moxifloxacin 1 It's crucial to weigh the benefits and risks of taking Zofran in your situation and consider alternative treatments that don't pose a risk to your cardiac health.

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)].

The use of 8 mg of ondansetron with a QTc interval of 480 ms is not explicitly addressed in the label. However, the label does mention that ECG monitoring is recommended in patients with conditions that may lead to QT prolongation.

• The label recommends avoiding ondansetron in patients with congenital long QT syndrome.
• Since a QTc interval of 480 ms is considered prolonged, caution should be exercised when administering ondansetron in this context.
• Given the potential risk of QT prolongation and Torsade de Pointes, it is advisable to monitor the patient's ECG and consider alternative treatments if possible 2.

From the Research

QT Interval Prolongation and Zofran

• The use of Zofran (ondansetron) has been associated with QT interval prolongation, which can increase the risk of torsades de pointes (TdP) and sudden cardiac death 3.
• A study found that 4 mg of intravenous ondansetron caused a mean prolongation of the QTc by 20 ms, with a mean proportion change from baseline of 5.2% 3.
• However, another study suggested that the clinical impact of QTc prolongation caused by ondansetron is questionable, as there were no reported serious adverse cardiac electrical events 3.

Risk Factors for QTc Prolongation

• Several risk factors can contribute to QTc prolongation, including hypokalemia, use of diuretics, antiarrhythmic drugs, and QTc-prolonging drugs 4.
• A study found that very strong evidence exists for hypokalemia, use of diuretics, antiarrhythmic drugs, and QTc-prolonging drugs of list 1 of CredibleMeds as risk factors for QTc prolongation 4.
• Other factors, such as hyperlipidemia, use of digoxin or statins, neurological disorders, diabetes, renal failure, depression, alcohol abuse, heart rate, pulmonary disorders, hormone replacement therapy, hypomagnesemia, history of a prolonged QTc-interval/Torsade de Pointes, familial history of cardiovascular disease, and the use of only QTc-prolonging drugs of list 2 or 3 of CredibleMeds, have little or no evidence as risk factors for QTc prolongation 4.

QTc Interval and Zofran Dosage

• A study recommended that when the QTc interval is 470-500 ms for males, or 480-500 ms for females, or the QTc interval increases 60 ms or more from pretreatment values, dose reduction or discontinuation of the offending drug should be considered where possible, and electrolytes corrected as needed 5.
• Given that the QTc interval is 480 ms, it is within the range where dose reduction or discontinuation of the offending drug should be considered, especially if the patient is female 5.
• However, the specific dosage of 8 mg of Zofran was not mentioned in the studies, and therefore, it is unclear whether this dosage would be safe for a patient with a QTc interval of 480 ms.

Monitoring and Prevention

• Close monitoring for QTc prolongation is necessary to prevent TdP, especially in patients with risk factors for QTc prolongation 5, 4.
• 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.
• Electrolytes should be corrected as needed, and the offending drug should be discontinued if the QTc interval is ≥500 ms 5.