Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.
GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.
The updated label will say that ondansetron, a 5-HT3 receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.
The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.
Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.
The FDA, which required GlaxoSmithKline to conduct the study, "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 FDA said.
It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.
Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.
The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.