Triacetyluridine
Also known as: Triacetyluridine, TAU, Uridine Triacetate
Overview
Triacetyluridine, also known as Uridine Triacetate (TAU), is a synthetic uridine derivative primarily used as an antidote for life-threatening toxicity induced by the chemotherapeutic agents 5-fluorouracil (5-FU) and capecitabine. It is administered orally and has demonstrated improved bioavailability compared to uridine. Its primary application is in treating severe toxicities resulting from 5-FU or capecitabine overexposure, particularly in patients with DPD deficiency or those experiencing early-onset severe toxicity. Clinical trials have shown significant survival benefits when administered promptly, ideally within 96 hours of exposure. Research is mature, with high-quality evidence supporting its efficacy as an antidote, making it a crucial intervention in managing chemotherapy-related complications.
Benefits
Triacetyluridine's primary benefit is significantly reducing mortality from 5-FU and capecitabine toxicity. Clinical trials have demonstrated a substantial survival advantage, with 96% of patients receiving uridine triacetate surviving compared to 16% with supportive care alone. This survival benefit is most pronounced when administered within 96 hours of exposure. Additionally, it allows for the potential resumption of chemotherapy in some patients. It is particularly beneficial for patients with DPD deficiency or those experiencing early-onset severe toxicity. The high survival rate observed in clinical trials underscores its clinical significance as an effective antidote.
How it works
Triacetyluridine functions by competing with fluorouridine triphosphate (FUTP) for incorporation into RNA. This competition mitigates the toxic effects of 5-FU and capecitabine, which disrupt RNA function and lead to cellular damage. By preferentially binding to the enzymes responsible for RNA synthesis, triacetyluridine reduces the incorporation of FUTP into RNA, thereby lessening the toxic effects on rapidly dividing cells, particularly in the gastrointestinal and hematologic systems. Its improved oral bioavailability ensures efficient absorption and rapid action, making it an effective antidote in emergency situations.
Side effects
Triacetyluridine is generally well-tolerated, with most side effects being mild and transient. Common side effects, occurring in more than 5% of patients, include vomiting (8.1%), nausea (4.6%), and diarrhea (3.5%). Uncommon side effects, occurring in 1-5% of patients, are not specifically reported in the available literature. Rare side effects, occurring in less than 1% of patients, are also not detailed. No significant drug interactions or contraindications have been reported. It is considered safe for pediatric use. Overall, triacetyluridine has a favorable safety profile, making it a valuable antidote for chemotherapy-induced toxicity.
Dosage
The recommended dosage of triacetyluridine is 10 g orally every 6 hours for a total of 20 doses. Administration should commence as soon as possible after recognizing toxicity from 5-FU or capecitabine exposure, ideally within 96 hours. This regimen is designed for emergency treatment of severe toxicity. While a maximum safe dose is not explicitly defined beyond this regimen, it is crucial to adhere to the prescribed dosage to minimize potential adverse effects. The oral formulation is preferred due to its improved bioavailability compared to uridine. No specific cofactors are required for its administration.
FAQs
When should triacetyluridine be administered?
Administer triacetyluridine as soon as possible after recognizing toxicity from 5-FU or capecitabine exposure, ideally within 96 hours, to maximize its effectiveness.
What are the common side effects of triacetyluridine?
The most common side effects are mild and include vomiting, nausea, and diarrhea. These are generally well-tolerated and transient.
Is triacetyluridine a preventative measure?
No, triacetyluridine is not a preventative measure. It is an antidote specifically for treating toxicity resulting from 5-FU or capecitabine exposure.
How effective is triacetyluridine?
Clinical trials have shown a significant reduction in mortality from 5-FU/capecitabine toxicity, with a 96% survival rate compared to 16% with supportive care alone.
Research Sources
- https://jhoponline.com/itp?view=article&secid=15242%3Arx-profiler-uridine-triacetate-an-antidote-to-life-threatening-5-fluorouracil-and-capecitabine-toxicity&artid=17263%3Auridine-triacetate-an-antidote-to-life-threatening-5-fluorouracil-and-capecitabine-toxicity&catid=4070 – This article discusses uridine triacetate as an antidote for life-threatening 5-fluorouracil and capecitabine toxicity. It highlights the clinical trials demonstrating a 96% survival rate with uridine triacetate compared to 16% with supportive care, emphasizing its efficacy in treating severe chemotherapy-induced toxicities.
- https://academic.oup.com/ijnp/article/21/6/550/4955527?login=false – This study investigates the effects of triacetyluridine on mood and brain pH. The research indicates that triacetyluridine may have potential benefits in improving mood and increasing brain pH in individuals with bipolar disorder, suggesting possible applications beyond its use as a chemotherapy antidote.
- https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.16319 – This article reviews the mechanisms and management of fluoropyrimidine toxicity. It emphasizes the importance of effective antidotes like uridine triacetate in mitigating the severe toxic effects associated with 5-FU and capecitabine, providing a comprehensive overview of the clinical strategies for managing these toxicities.
- https://www.researchgate.net/publication/5316221_Triacetyluridine_TAU_decreases_depressive_symptoms_and_increases_brain_pH_in_bipolar_patients – This research explores the effects of triacetyluridine (TAU) on depressive symptoms and brain pH in bipolar patients. The findings suggest that TAU may decrease depressive symptoms and increase brain pH, indicating potential therapeutic applications in managing bipolar disorder.
- https://www.liebertpub.com/doi/pdfplus/10.1089/cap.2010.0054 – This study focuses on the use of uridine triacetate in treating fluoropyrimidine overdose. It provides detailed insights into the clinical management of patients experiencing severe toxicity from 5-FU and capecitabine, highlighting the importance of timely administration of uridine triacetate to improve survival rates.
