After a yearlong investigation into the potential cardiac risks with the anti-nausea medication, Zofran, the FDA has announced that the 32 mg, single intravenous (IV) dose Zofran (ondansetron hydrochloride) will no longer be marketed because of the potential for serious cardiac risks.
Zofran is used to prevent chemotherapy-induced nausea and vomiting. But, has also been prescribed to pregnant women experiencing morning sickness, as well as in other situations where a patient felt nauseous.
In September of 2011 the U.S Food & Drug Administration announced that abnormal heart rhythms may be associated with use of Zofran (ondansetron), and were requiring GlaxoSmithKline (GSK), the manufacturer of Zofran the drug maker to thoroughly investigate the concern.
A drug safety communication issued on June 29, 2012, was a follow up of the September 2011 one and warned that the 32 mg, single IV dose should be avoided due to the risk of QT interval prolongation, which can lead to a serious and sometimes fatal heart rhythm called Torsades de Pointes. These drugs are sold pre-mixed in solutions of either dextrose or sodium chloride in plastic containers.
The FDA previously noted cardiovascular safety concerns that suggested Zofran (ondansetron) could cause QT prolongation, therefore required GSK, to conduct a thorough QT study to assess the potential for the drug to prolong the QT interval. Preliminary review of the study results shows that QT prolongation occurs in a dose-dependent manner. Specifically, at the highest tested single intravenous dose of 32 mg, the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower tested single intravenous dose of 8 mg, the maximum mean difference in QTcF from placebo after baseline-correction was 6 msec.
In the June Safety Communication the FDA announced that GSK was making changes to the Zofran drug label to remove the 32 mg single intravenous dose. They stated that the updated label would 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 three 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 new communication says that the FDA anticipates these products will be removed from the market through early 2013. FDA does not anticipate that removal of the 32 mg intravenous dose of ondansetron currently sold as pre-mixed injections will contribute to a drug shortage of IV ondansetron, as the 32 mg dose makes up a very small percentage of the current market.
The FDA continues to recommend the intravenous regimen of 0.15 mg/kg administered every 4 hours for three doses to prevent chemotherapy-induced nausea and vomiting. Oral dosing of ondansetron remains effective for the prevention of chemotherapy-induced nausea and vomiting. At this time, there is not enough information available for FDA to recommend an alternative single IV dose regimen.
Health care professionals are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.