The 32-mg intravenous dose of the antinausea drug ondansetron will no longer be marketed because it has been linked to a risk of QT prolongation, the Food and Drug Administration announced.
A statement on the agency’s MedWatch website said that the withdrawal of the 32-mg dose, available in premixed solutions of dextrose or sodium chloride, is expected to last through early 2013. Since this dose accounts for a "very small percentage" of the market, the voluntary withdrawal is not expected to contribute to a shortage of intravenous ondansetron, the Dec. 4 statement said.
The drug is marketed as Zofran and is available in generic formulations for preventing chemotherapy-induced nausea and vomiting. The FDA is recommending three doses of IV ondansetron at a dose of 0.15 mg/kg administered every 4 hours for three doses to prevent chemotherapy-induced nausea and vomiting but added: "If the calculated weight-based dose were to exceed 16 mg, the potential for prolonged QT interval would be greater; therefore, no single intravenous dose should exceed 16 mg." QT prolongation can result in the potentially fatal arrhythmia, torsades de pointes.
The FDA also stated that, currently, there is not enough information to recommend another single-dose intravenous regimen and that oral ondansetron "remains effective for the prevention of chemotherapy-induced nausea and vomiting."
Ondansetron also is approved for postoperative nausea and vomiting.
The announcement follows a previous FDA notice in June 2012 that the 32-mg single-IV dose of ondansetron should be avoided, citing preliminary results from a study suggesting that the 32-mg dose may cause QT prolongation. The agency first announced that it was conducting a safety review of ondansetron in September 2011.
At the time of the June 2012 statement, GlaxoSmithKline, the manufacturer of Zofran, which conducted the QT study, announced that it was removing the 32-mg single-IV dose from the drug’s label. In November, the labeling was revised and no longer includes the 32-mg IV dose; it includes information about QT prolongation and dosing information that no single-IV weight-based dose should exceed 16 mg.
Manufacturers of ondansetron intravenous products are Baxter Healthcare, Hospira, Teva, Bedford Labs, and Claris Lifesciences.
Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/default.htm.
