Treatment of Fluorouracil (5-FU) or Capecitabine Overdose with Uridine Triacetate
Uridine triacetate should be administered at a dose of 10 g orally every 6 hours for 20 doses within 96 hours following the end of 5-FU or capecitabine administration for overdose or early-onset severe toxicity. 1, 2
Indications for Uridine Triacetate
- Indicated for emergency treatment of adult and pediatric patients following fluorouracil or capecitabine overdose regardless of symptoms 2
- Indicated for patients exhibiting early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system 2
- Indicated for patients with unusually severe adverse reactions (e.g., gastrointestinal toxicity, neutropenia) within 96 hours following fluorouracil or capecitabine administration 1, 2
Administration Protocol
- Administer 10 g orally every 6 hours for a total of 20 doses (5-day course) 1
- Treatment should begin as soon as possible after overdose or recognition of severe toxicity 3
- Most effective when initiated within 24 hours of fluoropyrimidine administration, with decreasing efficacy when started later 3
- Must be administered within 96 hours of last fluoropyrimidine dose, as 50% mortality was observed in patients treated beyond this window 1
- Can be mixed with food (such as applesauce) to improve palatability and followed with water 4
- Consider antiemetic premedication (e.g., ondansetron) to prevent nausea and vomiting 4
Mechanism of Action and Efficacy
- Uridine triacetate is an oral prodrug of uridine that competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides 5
- Clinical trials demonstrated 96% survival rate in patients treated with uridine triacetate compared to only 16% survival in historical controls receiving supportive care alone 6, 1
- Provides rapid reversal of severe cardiac and neurologic toxicities 1
- Prevents or facilitates recovery from mucositis and leukopenia 6
- Allows 38% of patients to resume chemotherapy within 30 days (mean time to resumption: 19.6 days) 1, 6
Monitoring and Expected Outcomes
- Monitor for common adverse reactions including vomiting (8.1%), nausea (4.6%), and diarrhea (3.5%) 6
- Assess for resolution of fluoropyrimidine-related toxicities including:
- Laboratory values should be monitored daily during treatment 4
Important Considerations and Caveats
- Uridine triacetate is not recommended for non-emergency treatment of adverse reactions as it may diminish the efficacy of fluoropyrimidines 2
- The 96-hour window for administration is critical - efficacy decreases significantly after this timeframe 1, 3
- Consider testing for dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe toxicity, as this genetic variation increases risk of fluoropyrimidine toxicity 7
- For patients with known DPD deficiency requiring future fluoropyrimidine therapy, consider dose reductions (50% for heterozygous mutations) or alternative chemotherapy regimens (for homozygous mutations) 7
By following this protocol, healthcare providers can significantly improve survival and reduce morbidity in patients experiencing fluoropyrimidine overdose or severe toxicity.