The FDA is informing healthcare professionals and the public that preliminary results from a recently completed clinical study suggest that a 32 mg single intravenous dose of ondansetron (Zofran, and generics) may affect the electrical activity of the heart (QT-interval prolongation), which could pre-dispose the development of an abnormal and potentially lethal heart rhythm known as Torsades de Pointes in patients.
GlaxoSmithKline (GSK) has announced updates to the Zofran drug label to remove the 32 mg single intravenous dose. The updated label will state that the ondansetron can continue to be used in adults and children with chemotherapy-induced nausea and vomiting at the lower intravenous dose recommended in the drug label, a dose of 0.15 mg/kg administered every 4 hours for three doses; however, no single intravenous dose should exceed 16 mg. The updated label will include data from the new clinical study.
Ondansetron belongs to a class of medications called 5-HT3 receptor antagonists, used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy and surgery.
The FDA will evaluate the final study results, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults.
This new findings on QT-prolongation does not change any of the recommended oral dosing regimens for ondansetron, and it also does not change the recommended lower dose intravenous dosing used in the prevention of post-operative nausea and vomiting. The following is however now recommended:
- The use of a single 32 mg IV dose should be avoided. The new information indicates that QT prolongation occurs in a dose-dependent manner, and specifically at a single intravenous dose of 32 mg.
- Patients expressing a particular risk for QT-prolongation with ondansetron are those with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or patients taking concomitant medications that prolong QT interval.
- Electrolyte abnormalities (e.g. hypokalemia or hypomagnesia) should be corrected prior to infusion of ondansetron.
- Lower-dose IV regiment of 0.15 mg/kg every 4 hours for three doses may be used in adults on chemotherapy-induced nausea and vomiting. However, no single IV dose should exceed 16 mg due to risk of QT prolongation.
- None of the recommended oral dosing regimens, included the single oral dose of 24 mg for chemotherapy-induced nausea and vomiting are affected by the new information.