The FDA has issued new information about this safety issue, see the FDA Drug Safety Communication issued 6-29-2012

Safety Announcement

Additional Information for Patients

Additional Information for Healthcare Professionals

Data Summary

Safety Announcement

[09-15-2011] The U.S. Food and Drug Administration (FDA) is informing the public of an ongoing safety review of the anti-nausea drug Zofran (ondansetron, ondansetron hydrochloride and their generics). Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm.

Facts about Zofran (ondansetron and ondansetron hydrochloride) Used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy and surgery.

Is in a class of medications called 5-HT3 receptor antagonists. Works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting. 1

Available as 4 mg and 8 mg tablets, 4 mg and 8 mg orally disintegrating tablets, and oral solution (4 mg/5 mL). Also available as an injection for intravenous use (2 mg/mL).

Changes in the electrical activity of the heart (prolongation of the QT interval of the electrocardiogram [ECG]) — see Data Summary below — can lead to an abnormal and potentially fatal heart rhythm (including Torsade de Pointes). Patients at particular risk for developing Torsade include those with underlying heart conditions, such as congenital long QT syndrome, those who are predisposed to low levels of potassium and magnesium in the blood, and those taking other medications that lead to QT prolongation.

FDA has reviewed all available information and is making interim changes to the drug labels. The manufacturer of Zofran (GlaxoSmithKline) is being required to conduct a thorough QT study to assess the potential for the drug to prolong the QT interval. The results from this study are expected to be available in the summer of 2012. Additional label changes may result after the additional information has been reviewed.

The Zofran (ondansetron) drug labels already contain information about the potential for QT prolongation. The labels are being revised to include a warning to avoid use in patients with congenital long QT syndrome because these patients are at particular risk for Torsade. Additionally, recommendations for ECG monitoring in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or in patients taking other medications that can lead to QT prolongation, are being included in the labels.

Additional Information for Patients

Do not stop taking Zofran (ondansetron) without talking to your healthcare professional.

Discuss any questions or concerns about Zofran (ondansetron) with your healthcare professional.

While taking Zofran (ondansetron), your healthcare professional may occasionally 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 Zofran (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

ECG changes including QT interval prolongation have been seen in patients receiving Zofran (ondansetron). In addition, Torsade de Pointes, an abnormal heart rhythm, has been reported in some patients receiving ondansetron.

The use of Zofran (ondansetron) should be avoided in patients with congenital long QT syndrome.

ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking concomitant medications that prolong the QT interval.

Advise patients to contact a healthcare professional immediately if they experience signs and symptoms of an abnormal heart rate or rhythm while taking Zofran (ondansetron).

Report adverse events involving Zofran (ondansetron) to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.

Data Summary

The FDA previously noted cardiovascular safety concerns that suggested Zofran (ondansetron) could cause QT prolongation, which can lead to a serious and sometimes fatal heart rhythm called Torsade de Pointes. Additionally, there are articles published in the medical literature that describe QT interval prolongation with ondansetron or droperidol.2-4

FDA is now adding a new warning to avoid the use of ondansetron in patients with congenital long QT syndrome because these patients are at particular risk for developing Torsade. Previous versions of the ondansetron labels included a warning on ECG interval changes (QT interval prolongation). Additional recommendations for ECG monitoring in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or in patients taking other medications that can lead to QT prolongation, are being added to the ondansetron drug labels.

To further characterize this risk, FDA is requiring GlaxoSmithKline to conduct a thorough QT study to determine the degree to which Zofran (ondansetron) may cause QT interval prolongation. The FDA will continue to assess all available data supporting the safety and effectiveness of ondansetron and will update the public when more information becomes available.

References

National Center for Biotechnology Information. U.S. National Library of Medicine. PubMed Drug & Supplements Monograph Ondansetron. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601209.html. Accessed September 10, 2011. Charbit et al. Droperidol and ondansetron-induced QT interval prolongation. Anesthesiology 2008; 109(2): 206-212. Charbit et al. Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 2005; 102(6): 1094-1100. Nathan et al. Implicationa of Anesthesia in Children with Long QT syndrome. Anesthesia and Analgesia 2011; 112(5): 1163-1168.

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