FDA Drug Safety Communication: Updated information on 32 mg intravenous ondansetron (Zofran) dose and pre-mixed ondansetron products

This update is a follow-up to the FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran)¹ on 6/29/2012.

Safety Announcement
Table 1. List of ondansetron products to be voluntarily withdrawn from the U.S. market
Reference

Safety Announcement

[12-4-2012] The U.S. Food and Drug Administration (FDA) is notifying health care professionals that the 32 mg, single intravenous (IV) dose of the anti-nausea drug Zofran (ondansetron hydrochloride) will no longer be marketed because of the potential for serious cardiac risks. This dose has been removed from the Zofran drug label. FDA is now working with the manufacturers of all 32 mg dose ondansetron injectable products (brand and generic) to voluntarily recall them from the market. These drugs are sold pre-mixed in solutions of either dextrose or sodium chloride in plastic containers (See Table 1).

A previous Drug Safety Communication (DSC), issued on June 29, 2012², communicated that the 32 mg, single IV dose should be avoided due to the risk of a specific type of irregular heart rhythm called QT interval prolongation, which can lead to Torsades de Pointes, an abnormal, potentially fatal heart rhythm.

The 32 mg, single IV dose had been used to prevent chemotherapy-induced nausea and vomiting. As stated in the previous DSC, 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. 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. In addition, oral dosing of ondansetron³ 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.

FDA anticipates these products (see Table 1, below) to 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. According to sales distribution data, ondansetron IV 32 mg premixed bags accounted for less than 1% of ondansetron IV sales (vials, bags, etc.) from the manufacturers to retail and non-retail channels of distribution in the 12-month period ending in June 2012.¹

Table 1. List of ondansetron products to be voluntarily withdrawn from the U.S. market

Generic name	Sponsor	Application Number
Ondansetron Hydrochloride Injection, USP premix in Intravia Plastic Container	Baxter Healthcare Corporation	NDA 021915
Ondansetron Hydrochloride and Dextrose in Plastic Container	Hospira	ANDA 077348
Ondansetron Hydrochloride and Dextrose in Plastic Container	Teva	ANDA 077480
Ondansetron Hydrochloride and Dextrose in Plastic Container	Bedford Labs	ANDA 078291
Ondansetron Hydrochloride and Dextrose in Plastic Container	Claris Lifesciences	ANDA 078308