A 5-Fluorouracil-Induced Hyperammonemic Encephalopathy Challenged with Capecitabine

Abstract

Cancer patients presenting with altered mental status demand a broad differential with early recognition of the etiology. Failure to do so is associated with increased morbidity and mortality. Causes that must be considered include organ involvement of the cancer, electrolytes abnormalities, and even chemotherapeutic agents. A 32-year-old female patient had been recently started on FOLFOX for metastatic colon cancer. Her initial treatments were uneventful, but she later developed encephalopathy during day three of cycle five. During her evaluation, she was found to have hyperammonemia (84 mcmol/L), without hepatic failure, that resolved with stopping chemotherapy and supportive care. After a trial of home infusion fluorouracil, she developed hyperammonemic encephalopathy again. During both admissions, her symptoms resolved with IV hydration and cessation of chemotherapy. She was then successfully challenged with capecitabine (1000 mg/m 2 daily), and additional hydration, and continued chemotherapy without recurrence of symptoms. Hyperammonemia is associated with fluorouracil though the mechanism is unclear. Suspected etiologies include either elevated levels of the drug due to slower metabolism or accumulation of certain metabolites. Additionally, risk factors such urease-producing bacterial infections, dehydration, and increased catabolism are thought to increase the risk for hyperammonemia. This case demonstrates the need for greater awareness of fluorouracil as a cause of hyperammonemic encephalopathy. Knowledge of this may allow for earlier recognition and reduced unnecessary testing.

"5-Fluorouracil Neurotoxicity – Diagnostic and Clinical Implications"

“…In the literature on the subject, we can find several clinical papers devoted to the issue of 5-Fu neurotoxicity, the vast majority of which are case studies [3]. Two main patterns of encephalopathy are recognized.…”

“…Acute encephalopathies are usually rare, reversible and do not require treatment, although fatalities have also been reported rarely. In the described large group of 30 cases of hyperammonemic encephalopathies from the years 1986-2018, the mortality rate due to them was 17% (although the standards of diagnosis and treatment have changed over the last 30 years); 57% of patients were admitted to the ICU and 70% achieved complete neurological recovery within 5 [2][3][4][5][6][7][8][9][10] days. Rechallenge with 5-FU was considered in 14 (67%) neurologically recovered patients, and relapse was observed in 57% of these.…”

Connecting the dots: targeting gut microbiota in drug toxicity

“…FMT improved hepatic necrosis, intestinal mucosal barrier damage, behaviors, HE grade, and spatial learning capability of these rats (Wang et al, 2017), revealing that the gut microbiota can be a common target in treating liver and brain diseases. Besides, drugs such as 5-FU that induce hyperammonemia also may cause severe HE and should be given special attention in clinical use (Chahin et al, 2020). Theoretically, drugs eliciting hepatotoxicity or inducing hyperammonemia are potential in causing HE.…”

In silico Anticancer Activity and in vitro Antioxidant of Flavonoids in Plectranthus amboinicus

“…2 The main strategy of choice in the treatment of colon cancer is chemotherapy with 5-fluorouracil (5-FU) but it is very toxic to other normal tissues. [3][4] The diversity of plants in Indonesia is one of the important opportunities in developing Indonesia potential in the era of globalization. 5 Natural sources of antioxidants that come from food ingredients are found in spices, leaves, seeds, vegetables.…”