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The Food and Drug Administration has approved Vistogard (uridine triacetate) for the emergency treatment of adults and children who receive an overdose of the cancer chemotherapies fluorouracil (5-FU) or capecitabine, or who develop certain severe or life-threatening toxicities within four days of receiving these therapies. Vistogard blocks cell damage and cell death caused by fluorouracil.

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"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," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news 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."


Potentially life-threating or lethal toxicity from 5-FU can occur if the drug has been administered at a dose or rate greater than intended, or when a patient has genetic variations, impaired clearance or other factors that increase susceptibility to the toxicities of the drug. Overdose of 5-FU or capecitabine is rare, but when it occurs, the effects are serious and can be fatal, the FDA noted.


Vistogard, marketed by Wellstat Therapeutics Corporation, is an oral drug that should be taken as soon as possible after the overdose (whether or not the patient has symptoms) or early-onset (within four days) of severe or life-threatening toxicity. The patient's health care provider should determine when he or she should return to the prescribed chemotherapy after treatment with Vistogard, the FDA noted.


Safety and Efficacy

Safety and efficacy for Vistogard were evaluated in a study of 135 adult and pediatric patients with cancer who were treated in two separate trials and had either received an overdose of 5-FU or capecitabine, or had early-onset, unusually severe or life-threatening toxicities within 96 hours after receiving fluorouracil (not due to an overdose).


Of those treated with Vistogard for overdose, 97 percent of the patients were alive at 30 days, compared with 16 percent of patients in historical cases employing standard supportive care measures. Of those treated with Vistogard for early-onset severe or life-threatening toxicity, 89 percent were alive at 30 days. In both studies, 33 percent of patients resumed chemotherapy in less than 30 days.


"Severe 5-FU toxicity has, historically, been difficult to treat and sometimes resulted in death for those affected. It is important to recognize the signs of severe 5-FU and capecitabine toxicity early, which often include unexpected side effects on the first cycle-including gastrointestinal toxicities such as mucositis, central nervous system toxicities such as altered mental state, hematologic toxicities, and even cardiotoxicity," Wen Wee Ma, MD, Associate Professor of Oncology in the GI Cancers & Drug Development Program at Roswell Park Cancer Institute, who led the clinical development program for the drug, said in a news release.


Vistogard is not recommended for treating non-emergency adverse reactions associated with fluorouracil or capecitabine because Vistogard may lessen the efficacy of these drugs. The safety and efficacy of Vistogard initiated more than 96 hours following the end of treatment with 5-FU or capecitabine have not been established.


The most common side effects of treatment with Vistogard were diarrhea, vomiting, and nausea.


Other Designations

The FDA has also granted Vistogard orphan drug designation, which provides financial incentives, including clinical trial tax credits, user fee waivers, and eligibility for market exclusivity to promote rare disease drug development. The drug was also granted priority review and fast track designations, which are distinct programs intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions.


Clinical Quick Facts: Vistogard

Drug: Vistogard (uridine triacetate)


Approved Indication: Emergency treatment of adults and children who receive an overdose of the cancer chemotherapies fluorouracil or capecitabine, or who develop certain severe or life-threatening toxicities within four days of receiving these therapies


Common Side Effects: Diarrhea, vomiting, and nausea