Vistogard (uridine triacetate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Uridine triacetate, an acetylated prodrug of uridine and a pyrimidine analog, is a direct biochemical antagonist of fluorouracil and a uridine replacement agent.
Uridine triacetate is an acetylated prodrug of uridine and a pyrimidine analog. In fluorouracil or capecitabine overdosage or toxicity, uridine triacetate is a direct biochemical antagonist of fluorouracil. Excess circulating uridine derived from uridine triacetate is converted into uridine triphosphate (UTP), which competes with 5-fluorouridine triphosphate (FUTP; a cytotoxic intermediate metabolite of fluorouracil) for incorporation into RNA, thereby inhibiting cell damage and cell death.
In hereditary orotic aciduria, uridine triacetate provides an exogenous source of uridine for replacement therapy in patients who are unable to synthesize adequate quantities of uridine. Uridine can be used for the synthesis of uridine nucleotides by essentially all cells. Restoration of intracellular uridine nucleotide concentrations to within the normal range reduces the overproduction of orotic acid by feedback inhibition, thereby also reducing the urinary excretion of orotic acid.
Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body to form uridine. Uridine triacetate has a substantially higher oral bioavailability than uridine, providing fourfold to sixfold more uridine into the systemic circulation than equimolar oral doses of uridine. Uridine triacetate crosses the intestinal mucosa much more readily than uridine, and peak plasma concentrations of uridine following single-dose oral administration of uridine triacetate are generally achieved within 2-3 hours.
Administration of a slightly different formulation of uridine triacetate granules with food in healthy adults did not affect the overall rate and extent of uridine exposure compared with those observed following administration of the drug in the fasted state. Uridine crosses the blood-brain barrier. Circulating uridine is taken up by mammalian cells via specific nucleoside transporters.
Uridine can be excreted by the kidneys or metabolized by normal pyrimidine catabolic pathways present in most tissues. The elimination half-life of uridine is approximately 2-2.5 hours.
Uridine triacetate, formerly called vistonuridine, is commercially available in the US in 2 different oral formulations: Vistogard(R) granules, which are used for the treatment of fluorouracil or capecitabine overdosage or toxicity, and Xuriden(R) granules, which are used for the treatment of hereditary orotic aciduria.
Generic name: uridine triacetate
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Vistogard
Indications
The following indications are listed for Vistogard:
- Emergency Treatment Of Capecitabine Overdose
- Emergency Treatment Of Fluorouracil Overdose
- Emergency Treatment Of Severe Capecitabine Toxicity
- Emergency Treatment Of Severe Fluorouracil Toxicity
Also known as: Emergency Treatment Of Severe Adverse Effect Of Fluorouracil, Emergency Treatment Of Severe Adverse Event Of Capecitabine.
Dosing
Dosage of uridine triacetate is expressed in terms of the salt.
Uridine triacetate is administered orally as granules (e.g., Vistogard(R), Xuriden(R)) and may be given without regard to meals (see Description).
Opened packets or mixtures of uridine triacetate with food, milk, or infant formula should not be stored. Packets of the drug are for single use only; any unused portions should be discarded. Any granules left in an open packet should not be used for subsequent dosing.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Clinically important drug interactions with uridine triacetate have not been identified to date.
In vitro studies indicate that uridine triacetate and uridine do not have clinically important inhibitory effects on cytochrome P-450 (CYP) isoenzymes 3A4, 1A2, 2C8, 2C9, 2C19, 2D6, or 2E1. In vitro studies also indicate that uridine triacetate and uridine do not induce CYP isoenzymes 1A2, 2B6, or 3A4.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of uridine triacetate.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects occurring in more than 2% of patients receiving uridine triacetate (Vistogard(R)) for emergency treatment of fluorouracil or capecitabine overdosage or toxicity in clinical trials were vomiting, nausea, and diarrhea.
No adverse effects were reported in patients receiving uridine triacetate (Xuriden(R)) for the treatment of hereditary orotic aciduria in the principal efficacy study.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of uridine triacetate (Vistogard(R)) for emergency treatment following fluorouracil or capecitabine overdosage or early-onset, severe or life-threatening toxicity have been established in pediatric patients. Such use is supported by an open-label study that included 6 pediatric patients 1-16 years of age. Four of these pediatric patients were 1-7 years of age and received a body surface area-adjusted dosage of the drug.
Safety and efficacy of uridine triacetate (Xuriden(R)) for treatment of hereditary orotic aciduria have been established in a single open-label study in 4 pediatric patients 3 years of age or older and based on case reports of 18 pediatric patients who began uridine triacetate treatment at 2 months to 12 years of age.
Clinical response and safety of uridine triacetate in adults and pediatric patients are similar; however, data are limited. (See Uses.)
Limited case reports of uridine triacetate (Vistogard(R)) use during pregnancy are inadequate to inform a drug-associated risk of birth defects and miscarriage. There are no data regarding use of uridine triacetate (Xuriden(R)) in pregnant women to inform a drug-associated risk.
Animal studies have not revealed evidence of teratogenicity or fetal harm at uridine triacetate dosages of about one-half the maximum recommended human dosage of Vistogard(R) or 2.7 times the maximum recommended human dosage of Xuriden(R) administered to pregnant rats during the period of organogenesis.
It is not known whether uridine triacetate is distributed into human milk; effects of the drug on breast-fed infants or milk production also are not known. The benefits of breast-feeding and the woman's clinical need for uridine triacetate should be considered along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
In clinical studies evaluating uridine triacetate (Vistogard(R)) for treatment of fluorouracil or capecitabine overdosage or toxicity, 30% of patients were 65 years of age or older and 11% were 75 years of age or older. Clinical studies did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults.
In a population pharmacokinetic analysis, patient age (range: 20-83 years) did not substantially affect uridine pharmacokinetics.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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