U.S. FDA Approves First Chemotherapy Overdose Reversal Agent

The U.S. Food and Drug Administration (FDA) has approved uridine triacetate for the emergency treatment of adults or children with cancer who receive an overdose of the chemotherapeutic agents fluorouracil or capecitabine or who develop certain severe or life-threating toxicities within four days of receiving these agents. This is the first reversal agent of its kind to be approved by the U.S. FDA.

Uridine triacetate is administered orally and blocks cell damage and death from chemotherapy. The manufacturers note that uridine triacetate should be administered as soon as possible after an overdose occurs, though it can be administered up to four days following chemotherapy administration.

The drug’s approval was based on the findings of two separate trials that included 135 adult and pediatric patients with cancer. Patients included in the studies had either received an overdose of fluorouracil or capecitabine or had early-onset, unusually severe, or life-threatening toxicities within 96 hours of receiving the two chemotherapy drugs. The study’s primary endpoint was survival at 30 days or, if prior to 30 days, until the point at which chemotherapy could be resumed.

In the study, 97 percent of patients treated with uridine triacetate for overdose were alive at 30 days, while 89 percent of patients treated with uridine triacetate for toxicity were alive at 30 days. In both patient cohorts, 33 percent of patients resumed chemotherapy in less than 30 days.

The most common treatment-related adverse events (AEs) included diarrhea, vomiting, and nausea.

Uridine triacetate is not recommended for treating non-emergency AEs associated with fluorouracil or capecitabine. The safety and efficacy of uridine triacetate initiated more than 96 hours following chemotherapy has not yet been studied.

Source: U.S. FDA news release, December 11, 2015.