not-yet-known not-yet-known not-yet-known unknown 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 which 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 pre-screening 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 30days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120-504 hours after last fluoropyrimidine administration suggesting efficacy beyond the FDA licensing 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.

Abstract Prescription medicine misuse, especially misuse of opioids has become a major public healthcare issue in many developed countries such as the United States of America and Australia where this is associated with significant morbidity (Emergency Department visits due to acute toxicity) and mortality. In this review, we looked at the available data obtained from peer-reviewed articles and population surveys to gain an insight into the current situation in the Asia Pacific region. There is currently limited information available, but data from subpopulation surveys in a number of countries suggests that prescription medicine misuse is likely to be an issue of concern from a public health perspective in the Asia Pacific region. The available data suggest that misuse prevalence rates and the medicines that are commonly misused are similar to countries such as the USA and United Kingdom. Further studies are required to determine the overall prevalence of misuse, the harms associated with this and the sources of drugs being misused so that appropriate interventions can be implemented to tackle issues related to prescription medicine misuse in this region. Keywords: Prescription medicine misuse, drug abuse, opioids, benzodiazepines, GABA analogues