“ The patient’s symptoms resolved after permanently stopping 5-FU and administering lactulose and intravenous fluids, therefore supporting the diagnosis of hyperammonemic encephalopathy due to 5-FU. ”
BUFFALO, NY — February 5, 2026 — A new case report was published in Volume 12 of Oncoscience on December 23, 2025, titled “ Silent toxicity: A rare case of 5-fluorouracil-induced hyperammonemic encephalopathy .”
In this report, Areti Kalfoutzou from the National and Kapodistrian University of Athens and colleagues describe a rare and potentially life-threatening complication called hyperammonemic encephalopathy, which is linked to the widely used chemotherapy drug 5-fluorouracil (5-FU). The case highlights the importance of monitoring neurological symptoms in patients receiving 5-FU, even when liver function appears normal.
Hyperammonemic encephalopathy is a serious condition caused by elevated levels of ammonia in the blood, leading to acute confusion, reduced consciousness, and other neurocognitive disturbances. The case involves a 63-year-old woman with a history of pancreatic cancer who had undergone multiple surgeries and chemotherapy. Following several cycles of a regimen that included 5-FU, she developed repeated episodes of confusion and lethargy. Despite normal liver function, laboratory tests revealed significantly elevated serum ammonia levels.
“ Her past medical history included epileptic seizures, diabetes mellitus and hypothyroidism.”
Upon discontinuation of 5-FU and administration of standard treatments for hyperammonemia, including lactulose and intravenous fluids, the patient’s neurological symptoms resolved rapidly. The improvement strongly supported the diagnosis. Using the Naranjo adverse drug reaction probability scale, the authors identified 5-FU as the most likely cause of the toxicity.
The researchers also considered other medications the patient was taking, including antiepileptic drugs and irinotecan, which have also been associated with hyperammonemia. However, the pattern of symptom recurrence following each 5-FU infusion, and resolution after discontinuation, reinforced its role as the primary trigger.
Although 5-FU is commonly used to treat gastrointestinal and other solid tumors, it may affect ammonia clearance by disrupting energy metabolism and liver detoxification pathways. When ammonia accumulates in the bloodstream, it can cross the blood-brain barrier and cause neurotoxic effects, even in patients without liver impairment.
This case reinforces the need for clinicians to be vigilant when treating cancer patients with 5-FU. Early recognition of altered mental status and immediate testing of serum ammonia levels can lead to timely intervention, preventing serious outcomes. The authors advise careful consideration before reintroducing 5-FU and recommend doing so only in close collaboration with specialists in metabolic or drug-related toxicities.
DOI: https://doi.org/10.18632/oncoscience.638
Correspondence to: Areti Kalfoutzou – areti.kalfoutzou@haf.gr
Abstract video: https://www.youtube.com/watch?v=30iB3ZmCvJA
Keywords: oncology, hyperammonemia, encephalopathy, fluorouracil, neurotoxicity
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Silent toxicity: A rare case of 5-fluorouracil-induced hyperammonemic encephalopathy
23-Dec-2025
Authors have no conflicts of interest to declare.