Uridine triacetate
Regulatory sources consulted
Approved indications
- Emergency treatment in adults and paediatric patients after fluorouracil or capecitabine overdose, or for early-onset severe or life-threatening toxicity within 96 hours after the end of administration. It is not recommended for non-emergent adverse reactions because it may diminish antineoplastic efficacy; safety and efficacy have not been established when started after 96 hours.
Adverse events
Common (≥1%)
Vomiting · Nausea · Diarrhoea
Pregnancy and lactation
Limited pregnancy case reports are insufficient to establish a drug-associated risk. There are no data on presence in human milk; weigh breastfeeding benefits with the mother’s clinical need and potential infant risk.
Recent literature (PubMed)
In 2015, the United States Food and Drug Administration (FDA) approved uridine triacetate to treat overdose and severe toxicity of the fluoropyrimidine chemotherapy agents 5-fluorouracil (5-FU) and its oral prodrug capecitabine. Uridine triacetate is as an oral prodrug of uridine that competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides. Two million people worldwide start fluoropyrimidine chemotherapy each year, with 20-30% developing severe or life-threatening adverse effects, often attributable to a genetic predisposition such as dihydropyrimidine dehydrogenase deficiency. Whilst genetic prescreening is recommended prior to starting fluoropyrimidine agents, this only prevents 20-30% of early-onset life-threatening toxicity and so does not obviate the need for an antidote. Initial in-human studies established that uridine triacetate more than doubles the maximum tolerated weekly 5-FU bolus dose. A lack of clinical equipoise meant a placebo-controlled phase III trial was not ethical and so the phase III trials used historical controls. These found that uridine triacetate improved survival in those with fluoropyrimidine overdose and severe toxicity from 16% to 94%, with 34% able to resume chemotherapy within 30 days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120-504 h after last fluoropyrimidine administration, suggesting efficacy beyond the FDA licencing indications. Mechanistically uridine triacetate would be expected to be effective for overdose and severe toxicity of tegafur (a 5-FU prodrug), but there are no published case reports describing this. Uridine triacetate is available internationally through an expanded access scheme and has been available in the UK since 2019 on a named patient basis. Capecitabine (brand name Xeloda) is a chemotherapy agent that belongs to the drug class of fluoropyrimidines. It is widely used in the treatment of several mal
Capecitabine is an anticancer drug related to 5-fluorouracil (5-FU) that is used to treat multiple cancers. Little is known about the central nervous system toxicity of capecitabine owing to the low frequency of occurrence. In this report we describe a rare case of capecitabine-related toxic encephalopathy involving the cerebellum and subcortical white matter. A review of the literature showed that most reported cases have shown excellent recovery within a few days of capecitabine termination. Whether uridine triacetate is a reasonable treatment choice for patients with life-threatening toxic encephalopathy depends on the availability of reliable clinical data. Prescreening for dihydropyrimidine dehydrogenase genotype variants and detection of 5-FU degradation rate prior to capecitabine treatment may become an effective way to avoid toxic reactions by regulating the therapeutic dose for each patient, which remains to be investigated and needs more clinical data to support.