5-Fluorouracil Overdose Symptoms
5-FU overdose causes life-threatening toxicities including severe gastrointestinal symptoms (bloody diarrhea, stomatitis, vomiting), myelosuppression (neutropenia, thrombocytopenia), neurotoxicity (encephalopathy, ataxia, dysarthria), and cardiotoxicity (chest pain, arrhythmias). 1
Gastrointestinal Toxicity
The most prominent and dangerous manifestations of 5-FU overdose involve the GI tract:
- Severe diarrhea (watery or bloody) that can be life-threatening 2
- Stomatitis and mucositis - severe inflammation and ulceration of oral and GI mucosa 1, 3
- Vomiting 3
- Severe abdominal pain 1
- Fever and chills 1
The disruption of gut lining integrity permits enteric organisms to enter the bloodstream, creating risk for overwhelming sepsis, particularly when coinciding with neutropenia 2. This combination has historically resulted in a 5% mortality rate in some series 2.
Hematologic Toxicity
Myelosuppression is a cardinal feature of 5-FU overdose 3:
- Neutropenia - potentially life-threatening 1
- Thrombocytopenia 1, 4
- Pancytopenia 2
- Leukocytosis (paradoxically, the most frequent hematological side effect at therapeutic doses) 1
Neurotoxicity
Neurological symptoms are rare but potentially fatal 5, 6:
- Encephalopathy with altered consciousness ranging from hypoactive delirium to coma 5, 7
- Ataxia 5
- Dysarthria 5
- Convulsions 6
- Toxic leukoencephalopathy - affects white matter, can present acutely or subacutely 7
- Cerebral vasospasm presenting as stroke-like symptoms 8
MRI findings in neurotoxicity cases show diffusion restriction with T2/FLAIR hyperintensities in bilateral centrum semiovale, white matter, and corpus callosum 7. Symptoms typically develop within 3-6 days of administration 7, 6.
Cardiovascular Toxicity
Angina-like chest pain is the most commonly described cardiac effect, with incidence ranging from 1% to 68% 9:
- Cardiac events typically occur within 5 days after first administration 9
- Ischemic ECG changes reported in 68% of patients 9
- Supraventricular arrhythmias and flutter requiring cardioversion 4
- Possible mechanisms include coronary artery thrombosis, vasospasm, and direct myocardial toxicity 9
Dermatologic Manifestations
Critical Risk Factors for Severe Toxicity
Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at extreme risk for life-threatening complications 2, 1. However, severe neurotoxicity can occur even with normal DPD activity 5, making clinical vigilance essential regardless of genetic testing results.
Timing of Symptom Onset
Symptoms are often delayed, which poses a diagnostic challenge 3. Patients may not seek medical attention until many hours or several days after administration, as toxicity manifestations typically appear:
- Cardiac symptoms: within 5 days 9
- Neurological symptoms: 3-6 days 7, 6
- GI symptoms: variable, but can be immediate to several days
Treatment Considerations
Uridine triacetate (Vistogard®) is FDA-approved as the specific antidote and must be administered within 96 hours following the end of 5-FU administration 3. In clinical trials, 96% of patients recovered with uridine triacetate versus only 10% in historical controls 3. However, some patients have been successfully managed with best supportive care alone 10.