Mechanism of Action (MOA)

Vistogard® (uridine triacetate) oral granules inhibit severe 5-FU toxicity3,4

Vistogard
  • Studies have demonstrated that uridine does not interfere with 5-FU disruption of DNA synthesis; however, this has not been established in clinical trials5,6
 
  • Following oral administration, Vistogard® yields uridine in circulation. Uridine competitively inhibits cell damage and cell death caused by 5-FU
  • 5-FU interferes with nucleic acid metabolism (DNA and RNA) in normal and cancer cells. Cells anabolize 5-FU to the cytotoxic intermediates FdUMP (5-fluoro-2’-deoxyuridine-5’-monophosphate) and FUTP (5-fluorouridine triphosphate)
  • FdUMP inhibits synthesis of thymidine, which is required for DNA replication and repair. Uridine is not found in DNA
  • The incorporation of FUTP into RNA is a major source of 5-FU cytotoxicity. Excess circulating uridine derived from Vistogard® is converted into UTP (uridine triphosphate), which competes with FUTP for incorporation into RNA
  • Vistogard® inhibits incorporation of FUTP into RNA, a major source of 5-FU toxicity

Important Safety Information

  • In clinical studies, adverse reactions occurring in >2% of patients receiving VISTOGARD included vomiting (10%), nausea (5%), and diarrhea (3%).
  • One person receiving uridine triacetate experienced grade 3 nausea and vomiting.
  • VISTOGARD was discontinued for adverse reactions in 2 (1.4%) patients.