5-fluorouracil poisoning

5-Fluorouracil (5-FU) poisoning, also known as 5-fluorouracil toxicity, refers to severe and potentially life-threatening adverse reactions to the chemotherapy drug 5-fluorouracil or its oral prodrug capecitabine. 5-Fluorouracil is widely used in the treatment of solid tumors including colorectal, breast, head and neck, and gastrointestinal cancers. Toxicity occurs when the drug accumulates to dangerous levels in the body, most commonly due to a deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. DPD is responsible for metabolizing over 80% of administered 5-FU, and patients with partial or complete DPD deficiency are at significantly increased risk of severe poisoning even at standard therapeutic doses. The condition affects multiple body systems. Hematologic toxicity manifests as severe neutropenia, leukopenia, thrombocytopenia, and pancytopenia, which can lead to life-threatening infections and bleeding. Gastrointestinal effects include severe mucositis, stomatitis, intractable diarrhea, nausea, and vomiting. Neurological toxicity can present as cerebellar ataxia, encephalopathy, confusion, and altered consciousness. Cardiac toxicity, including chest pain, arrhythmias, and cardiomyopathy, may also occur. Dermatologic manifestations such as hand-foot syndrome and severe dermatitis are common. In the most severe cases, multi-organ failure and death can result. Treatment of 5-FU poisoning includes immediate discontinuation of the drug and supportive care. Uridine triacetate (Vistogard) is an FDA-approved antidote that, when administered within 96 hours of the last dose of 5-FU or capecitabine, can significantly reduce mortality by competitively inhibiting the incorporation of toxic 5-FU metabolites into RNA. Preventive pharmacogenomic testing for DPYD variants before initiating 5-FU-based chemotherapy is increasingly recommended by clinical guidelines to identify at-risk patients and adjust dosing accordingly.

Common questions about 5-fluorouracil poisoning