Fluorouracil-induced neurotoxicity: risk factors, clinical impact, and management strategies

Abstract

Neurotoxicity is a rare ADR of 5-FU and may present with nonspecific symptoms.

Reduced DPD activity increases the risk of 5-FU-related ADRs and should be assessed before initiating therapy.

Uridine triacetate has been approved as an antidote in the U.S. for several years and is available as an unlicensed product in the EU and other regions. The recommended dosage is 10 g orally every 6 hours for a total of 20 doses (for children: 6.2 g/m² BSA, max. 10 g per dose). Non-acetylated uridine, when used as an alternative, has significantly lower bioavailability, resulting in lower uridine concentrations.

When assessing a suspected ADR, factors such as temporal correlation, drug interactions, elimination disorders, and enzyme polymorphisms should be considered. Suspected ADRs should be reported to Swissmedic, with mandatory reporting required for severe adverse reactions by healthcare professionals.