FDA Approves Rescue Drug for Chemotherapy Overdose

The US Food and Drug Administration (FDA) granted approval to uridine triacetate (Vistogard, Wellstat Therapeutics) as a treatment for overdose of fluorouracil or capecitabine, which are administered for a number of malignancies.

“Treating cancer requires not only selecting which drug may be most effective and well tolerated, but ensuring the correct dose is given at proper intervals. While rare, unintentional overdose can occur,” said Richard Pazdur, MD, director of the FDA’s Office of Hematology and Oncology Products, in a press release. “Today’s approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents.”

Uridine triacetate is orally administered, and quickly converts to uridine, which is a pharmacologic antidote to fluorouracil. The FDA noted that it can block cell damage and cell death caused by fluorouracil. The approval comes after uridine triacetate was granted orphan drug designation, which promotes development of agents for rare conditions or diseases, as well as priority review and fast track designation. Wellstat Therapeutics submitted the application for review in September 2015.

The FDA based its decision on results from two separate open-label trials that included a total of 135 adult and pediatric cancer patients. All patients either received an overdose of fluorouracil or capecitabine or had early-onset and unusually severe or life-threatening toxicities within 96 hours of receiving fluorouracil.

Of those patients treated for overdose, 97% were alive after 30 days. Of those treated for early-onset severe toxicity, 89% were alive at 30 days. A total of 33% of patients were able to resume chemotherapy treatments for their cancers within 30 days of the uridine triacetate treatment. The most common adverse events with the agent were diarrhea, vomiting, and nausea.

The FDA specifically noted that the efficacy of the treatment when administered more than 96 hours following fluorouracil or capecitabine treatment remains unknown.

According to Wellstat Therapeutics, as many as 8,250 patients each year in the United States develop severe toxic reactions to fluorouracil, with as many as 1,300 dying from the toxicity. A presentation of clinical experience with uridine triacetate at the 2010 American Society of Clinical Oncology Annual Meeting noted that of 43 historical cases of fluorouracil overdose identified, 39 proved fatal.