Preclinical data for VISTOGARD® (uridine triacetate)
Earlier treatment improved survival in animal studies1
After a lethal dose of 5-FU in animal studies1
when VISTOGARD dosing began at 24 hours1
Treatment with VISTOGARD (2 g/kg every 8 hours for 15 doses over
5 days) was initiated at 24, 48, 74, and 96 hours (n=10/group) after a lethal overdose of 5-FU
(300 mg/kg) in normal mice and in a model of DPD delivery.14
The clinical significance of animal studies is unknown
Survival diminished with increasing intervals between the 5-FU dose and uridine triacetate
treatment, indicating that earlier administration is more beneficial1
In mice given a sub-lethal dose of 5-FU, the administration of oral uridine triacetate
diminished but did not completely prevent hematological toxicity as a function of increasing
dose1
Clinical data
The first and only FDA-approved emergency treatment following 5-FU or
capecitabine overdose, or early-onset, severe toxicity occurring within 96 hours of
administration1,2
Ma WW, Saif MW, El-Rayes, BF et al (2017), Emergency Use of
Uridine Triacetate for the Prevention and Treatment of Life-Threatening
5-Fluorouracil and Capecitabine Toxicity. Cancer 123(2):345-356
Ison G et al. (2016), FDA approval: Uridine triacetate for the treatment
ofpatients following fluorouracil or capecitabine overdose or exhibiting
early-onset severe toxicides following administration of these drugs. Clin
Cancer Res 22(18): 1-5
Brutcher E et al. (2018) Assessment and Treatment of Uncommon, Early-
onset, Severe Toxicides Associated With 5-Fluorouracil and
Capecitabine. Clin J Oncology Nursing 22 (6): 627-634
Polk A. et al. (2016). Incidence and risk factors for capecitabine-induced
symptomatic cardiotoxicity: A retrospective study o f452 consecutive
patients with metastatic breast cancer. BMJ Open, 6, e012798
Genentech, Inc. (2016). Xeloda® (capecitabine) Package Insert
Meulendijks, D et al. (2016) Renal function, body surface area, and age
are associated with risk of early-onset fluoropyrimidine-associated
oxicity in patients treated with capecitabine-based anticancer regimens
in daily clinical care. European Journal of Cancer, 54, 120-130
Froehlich TK et al. (2015). Clinical importance of risk variants in the
dihydropyrimidine dehydrogenase gene for the prediction of early-onset
fluoropyrimidine toxicity. International Journal of Cancer, 136, 730-739
Mitani S et al. (2017) Acute hyperammonemic encephalopathy after
fluoropyrimidine-based chemotherapy: A case series and review of the
literature Medicine 96:22(e6874)
Etienne-Grimaldi M-C et al. (2017) New advances in DPYD genotype
and risk of severe toxicity under capecitabine. PLOS ONE, 12, e0175998
Hamzic S et al. (2018) Come a long way, still a ways to go: from
predicting and preventing fluoropyrimidine toxicity to increased
efficacy? Pharmacogenomics 19(8):689-692 Published Online: 22 May
2018
Rodriguez RU. Public teleconference regarding licensing and
collaborative research opportunities for: methods and compositions
relating to detecting dihydropyrimidine dehydrogenase (DPD). Fed
Regist. 2008; 73(129):38233
Andre T et al. (2004) Oxaliplatin, fluorouracil, and leucovorin as
adjuvant treatment for colon cancer N Engl J Med. 2004;350: 2343-2351
Sara JD et al. (2018) 5-fluorouracil and cardiotoxicity: a review
Therapeutic Advances in Medical Oncology Vol 10: 1-18
Peng J et al. (2018) Cardiotoxicity of 5-fluorouracil and capecitabine in
Chinese patients: a prospective study Cancer Communications; 38(22):
1-7
Yeh KH and Cheng AL (1997) High-dose 5-fluorouracil infusional
herapy is associated with hyperammonaemia, lactic acidosis and
encephalopathy Brit. J Cancer 75(3): 464-465
Cordier P-Y et al. (2011). 5-FU-induced neurotoxicity in cancer patients
with profound DPD deficiency syndrome: A report of two cases. Cancer
Chemotherapy and Pharmacology, 68, 823-826
BTG International Inc. (2023) Vistogard (uridine triacetate) Oral Granules Package Insert
Garcia R et al. (2018) Prompt treatment with uridine triacetate improves
survival and reduces toxicity due to fluorouracil and capecitabine
overdose or dihydropyrimidine dehydrogenase deficiency Toxicology
and Applied Pharmacology 353 (2018) 67-73
Baldeo C et al. (2018) Uridine triacetate for severe 5-fluorouracil
toxicity in a patient with thymidylate synthase gene variation: Potential
pharmacogenomic implications (Case Report). SAGE Open Medical
Case Reports Volume 6: 1-4
Vaudo CE et al. (2016) Early-Onset 5-Fluorouracil Toxicity in a Patient
Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical
Course of Reversal with Uridine Triacetate. Pharmacotherapy 36(11)
e178-e182
Santos C et al. (2017) The successful treatment of 5-fluorouracil (5-FU)
overdose in a patient with malignancy and HIV/AIDS with uridine
triacetate. American Journal of Emergency Medicine 35(5) 802.e7-
802.e8
Chu E (2014) Epidemiology and natural history of central venous access
device use and infusion pump function in the NO16966 trial Brit J Cancer
110, 1438-1445 doi: 10.1038/bjc
You are now leaving the patient site.
The section you selected contains information intended for U.S. healthcare professionals only.
Please certify that you are a U.S. healthcare professional by clicking the link below.
