[06-29-2012] The U.S. 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, ondansetron hydrochloride, and generics) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as 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 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.
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, FDA continues to assess data about the risk of QT prolongation and will update the public when more information becomes available. FDA previously issued a DSC about the ongoing safety review of ondansetron in September 2011.
- Discuss any questions or concerns about ondansetron with your healthcare professional.
- While taking ondansetron, your healthcare professional may order an electrocardiogram (ECG, EKG) to monitor your heart rate and rhythm.
- Seek immediate care if you experience an irregular heartbeat, shortness of breath, dizziness, or fainting while taking ondansetron.
- Report any side effects you experience to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.
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, an abnormal, potentially fatal, heart rhythm, 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 (e.g., hypokalemia or hypomagnesemia) should be corrected prior to the infusion of ondansetron.
- The lower dose intravenous regimen of 0.15 mg/kg every 4 hours for three 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.
- Report adverse events involving ondansetron to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.
GlaxoSmithKline (GSK), the manufacturer of Zofran, was required by FDA 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.