uridine triacetate

Action and Spectrum

Actions and spectrum: 

uridine triacetate is an orally bioavailable pro-drug of uridine, a naturally occurring nucleoside that plays a role in cellular metabolism and nucleic acid synthesis. uridine triacetate is used to treat patients with life-threatening overdoses of the chemotherapy drugs fluorouracil (5-FU) or capecitabine, or for treating hereditary orotic aciduria. 

In the case of 5-FU or capecitabine overdose, uridine triacetate rapidly restores depleted uridine levels, which helps mitigate the toxic effects of these chemotherapy drugs. In hereditary orotic aciduria, uridine triacetate supplementation can help compensate for a deficiency in the enzyme that converts orotic acid to uridine, which can cause severe growth and developmental delays if left untreated. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Vomiting (10%) 

Diarrhea (3%) 

Nausea (5%) 

Black Box Warning

Black Box Warning:  

uridine triacetate does not have a black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

uridine triacetate is contraindicated in patients with a known hypersensitivity to uridine triacetate or any of its components. It is also contraindicated in patients with hereditary fructose intolerance as there is a presence of sorbitol in the oral suspension formulation.  

Caution: 

• Renal Impairment: uridine triacetate is eliminated from the body primarily via the kidneys. Therefore, caution is required when using this medication in patients with renal impairment. 
• Hepatic Impairment: Patients with hepatic impairment may experience a higher risk of side effects when using uridine triacetate. The drug should be used with caution in such patients. 
• Pregnancy and lactation: The safety and efficacy of uridine triacetate have not been established in pregnant or lactating women.  
• Geriatric Population: Elderly patients may have reduced kidney function and may be more sensitive to the effects of uridine triacetate. Caution is advised when using this medication in the geriatric population. 
• Pediatric Population: The safety and efficacy of uridine triacetate have not been established in children. Therefore, this medication should only be used in children if the potential benefits justify the potential risks. 
• Drug Interactions: uridine triacetate may interact with other drugs that are metabolized by the liver.

Comorbidities: 

There are no specific comorbidities associated with the use of uridine triacetate. However, in patients with hepatic or renal impairment, it should be used with caution, as well as in those with a history of hypersensitivity reactions to any of the components of the medication. Additionally, patients with a history of seizures should be monitored closely when taking uridine triacetate, as it may increase the risk of seizures. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category C 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

uridine triacetate is a prodrug of uridine, a nucleoside that plays a role in the biosynthesis of cellular RNA and DNA. When administered, uridine triacetate is rapidly deacetylated by esterases in the blood and tissues, releasing uridine. Uridine is then incorporated into RNA and DNA, where it contributes to nucleic acid synthesis and repair processes. 

uridine triacetate has also been shown to increase plasma uridine concentrations, which can enhance mitochondrial function and promote neuroprotection. Additionally, it may have a protective effect against the toxic effects of chemotherapeutic agents such as fluorouracil, which can cause severe and sometimes fatal adverse reactions. 

uridine triacetate does not have any direct pharmacological activity itself but rather acts as a prodrug for uridine.  

Pharmacodynamics: 

uridine triacetate is a prodrug of uridine, which is converted to uridine in vivo. Uridine is a naturally occurring nucleoside that plays a vital role in the synthesis of RNA and DNA. uridine triacetate has been shown to increase the plasma concentrations of uridine, which can then be incorporated into RNA and DNA. This is thought to help promote DNA repair and reduce the toxic effects of chemotherapy. 

uridine triacetate has also been shown to enhance pyrimidine salvage, which is a process that recycles pyrimidine nucleotides and helps to maintain cellular integrity during periods of stress. By increasing pyrimidine salvage, uridine triacetate can help to support normal cellular function in the face of chemotherapy-induced damage. 

Overall, the pharmacodynamics of uridine triacetate is complex and multifactorial, involving a range of biochemical pathways and cellular processes. Its precise mechanism of action is still not fully understood, and further research is needed to elucidate the full extent of its pharmacodynamic effects.  

Pharmacokinetics: 

Absorption 

uridine triacetate is rapidly absorbed from the gastrointestinal tract, and the peak plasma concentration (Cmax) is reached within 1 to 2 hours after oral administration. The bioavailability of uridine triacetate is approximately 94%. 

Distribution 

uridine triacetate is rapidly hydrolyzed to uridine, which is widely distributed throughout the body. The volume of distribution (Vd) of uridine triacetate is approximately 400 L. 

Metabolism 

uridine triacetate is rapidly metabolized to uridine by esterases in the blood and tissues. Uridine is further metabolized to uridine diphosphate (UDP)-glucose and other nucleotides in the liver. 

Elimination and excretion 

Uridine and its metabolites are primarily excreted in the urine. The elimination half-life (t1/2) of uridine triacetate is approximately 0.7 hours. 

Adminstartion

Administration: 

uridine triacetate is available as oral tablets and should be taken with or without food. The tablet should be administered whole with a glass of water and not crushed, broken, or chewed.

The duration and dosage of treatment depend on the patient’s medical condition, response to treatment, and other medications they may be taking. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: uridine triacetate 

Pronounced: [ URE-i-deen-trye-AS-e-tate ]  

Why do we use uridine triacetate? 

uridine triacetate is a medication used for the emergency treatment of adult and pediatric patients who receive an overdose of capecitabine or fluorouracil, two chemotherapy drugs, or experience severe or life-threatening toxicity within 96 hours of receiving these drugs.

uridine triacetate works by providing an alternative pathway for the metabolism of fluorouracil and capecitabine, which reduces their toxicity. It is given orally in the form of tablets or powder for oral suspension.