December 11, 2015
On December 11, 2015, the U.S. Food and Drug Administration granted approval to uridine triacetate (VISTOGARD® granules, Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients:
following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration.
Uridine triacetate is not recommended for the non-emergent treatment of adverse reactions associated with fluorouracil or capecitabine because uridine triacetate may diminish the efficacy of these drugs. The safety and efficacy of uridine triacetate initiated more than 96 hours following the end of fluorouracil or capecitabine administration have not been established.
The approval of uridine triacetate is based on two single-arm, open-label, expanded access studies of patients who had either received a fluorouracil or capecitabine overdose or presented with severe or life-threatening toxicities within 96 hours after the end of receiving fluorouracil or capecitabine. The major efficacy outcome was survival at 30 days or the resumption of chemotherapy, if prior to 30 days. Of the 135 patients in the two studies, 130 (96%) survived and five (4%) died. Of the five patients who died, two were treated after 96 hours following the end of fluorouracil administration. Retrospective historical case reports of 25 patients who were overdosed with fluorouracil and received supportive care only, disclosed that 84% of patients died.
Safety data was evaluated in 135 patients enrolled on these two studies. The most common adverse reactions (greater than 2%) were vomiting (10%), nausea (5%) and diarrhea (3%). One patient receiving uridine triacetate experienced serious adverse reactions of grade 3 nausea and vomiting. Five deaths were reported within 30 days of the last dose of uridine triacetate. No deaths were attributable to uridine triacetate.
The recommended dose and schedule of uridine triacetate for adults is 10g orally every 6 hours for 20 doses. The recommended dose and schedule for pediatric patients is 6.2g/m2 of body surface area orally every 6 hours for 20 doses. Administer uridine triacetate as soon as possible after an overdose or early-onset toxicity within 96 hours following the end of 5-fluorouracil or capecitabine administration.
Uridine triacetate is being approved prior to the Prescription Drug User Fee Act (PDUFA) goal date of March 10, 2016. This application was granted an orphan designation and a fast track therapy designation. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).