December 6, 2012
FDA is alerting healthcare providers that ondansetron (Zofran, generics) 32 mg premixed bags will be voluntarily withdrawn from the U.S. market through early 2013 due to an increased risk of QT prolongation associated with this dose. Ondansetron is a 5-HT3 receptor antagonist used to treat and prevent nausea caused by chemotherapy, radiation therapy, and surgery. Use of a single intravenous (IV) dose of ondansetron 32 mg could cause QT interval prolongation, and predispose patients to cardiac arrhythmias. The risk of QT interval prolongation and cardiac arrhythmias with ondansetron is dose-related. Manufacturers of ondansetron 32 mg premixed bags include Baxter Healthcare Corporation, Bedford Labs, Claris Lifesciences, Hospira, and Teva.
Prior to September 2011, the product labeling stated that ondansetron may prolong the QT interval which can lead to Torsades de Pointes, a potentially fatal heart arrhythmia. Patients with existing heart conditions, such as congestive heart failure or bradyarrhythmias, or those with hypokalemia or hypomagnesemia are especially at risk for this effect.
In September 2011, FDA required that the product labeling for ondansetron include additional recommendations to avoid the drug in patients with congenital long QT syndrome and to monitor electrocardiogram in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and those taking other medications that prolong the QT interval.
A study completed by the manufacturer of Zofran in June, 2012 found that use of a single intravenous dose of ondansetron 32 mg could cause QT interval prolongation, and predispose patients to cardiac arrhythmias, including potentially fatal torsades de pointes. The product labeling has been revised to eliminate the 32 mg single IV dose from the dosing recommendations for the prevention of chemotherapy-induced nausea and vomiting (CINV). For the prevention of CINV in children and adults, the product label will recommend a lower dosage regimen of 0.15 mg/kg/dose IV every 4 hours for 3 doses, with each single dose not to exceed 16 mg – cap the IV dose at 16 mg in patients weighing more than 106 kg. The revised product labeling also advises using additional caution in patients with other risk factors for QT interval prolongation (eg, long QT syndrome, heart failure, bradycardia, other concomitant QT-prolonging medications), and recommends correcting electrolyte abnormalities prior to starting ondansetron therapy. There are no changes to dosage recommendations for postoperative nausea and vomiting, or to oral dosage recommendations for CINV.
Patients currently taking ondansetron should consult their healthcare professional before stopping the medication. Report ondansetron related adverse effects to the MedWatch program.
Additional information is available at the following links:
- MedWatch Alerts:
- December 4, 2012:
- June 29, 2012:
- September 15, 2011:
- December 4, 2012:
- Drug Safety Communications:
December 6, 2012; June 29, 2012; September 15, 2011; University of Utah, Drug Information Service. Copyright 2012, Drug Information Service, University of Utah, Salt Lake City, UT.