The US Food and Drug Administration (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) may cause QT interval prolongation, which could pre-dispose patients to develop Torsades de Pointes.
GlaxoSmithKline (GSK) has announced changes to the Zofran drug label to remove the 32-mg single intravenous dose. The updated label will state that 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 3 doses; however, no single intravenous dose should exceed 16 mg. Information from the new clinical study will be included in the updated drug label.
The FDA will evaluate the final study results when available, 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. The new information on QT prolongation does not change any of the recommended oral dosing regimens for ondansetron. It also does not change the recommended lower dose intravenous dosing of ondansetron to prevent post-operative nausea and vomiting. As part of the ongoing safety review of ondansetron, the FDA continues to assess data about the risk of QT prolongation and will update the public when more information becomes available. Additional Information for Healthcare Professionals (updated from 9/15/2011)· ECG changes including QT interval prolongation have been observed in patients receiving ondansetron. In addition, Torsade de Pointes has been reported in some patients receiving ondansetron.
- The use of a single 32-mg intravenous dose of ondansetron should be avoided. New information indicates that QT prolongation occurs in a dose-dependent manner, and specifically at a single intravenous dose of 32 mg.
- Patients who may be at particular risk for QT prolongation with ondansentron are those with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or patients taking concomitant medications that prolong the QT interval - Electrolyte abnormalities should be corrected prior to the infusion of ondansetron.
- The lower dose intravenous regimen of 0.15 mg/kg every 4 hours for 3 doses may be used in adults with chemotherapy-induced nausea and vomiting. However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation.
- The new information does not change any of the recommended oral dosing regimens for ondansetron, including the single oral dose of 24 mg for chemotherapy induced nausea and vomiting.
- The new information also does not change the recommended lower dose intravenous dosing to prevent post-operative nausea and vomiting.
SOURCE: US Food and Drug Administration