Uridine Triacetate

Uridine triacetate is an acetylated pro-drug of uridine. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation.

• VISTOGARD ® is indicated for the emergency treatment of adult and pediatric patients: following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. VISTOGARD ® is a pyrimidine analog indicated for the emergency treatment of adult and pediatric patients: following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration.

• None. None.contraindicated

Recommended Dosage Adults : 10 grams (1 packet) orally every 6 hours for 20 doses, without regard to meals. ( 2.1 ) Pediatric : 6.2 grams/m 2 of body surface area (not to exceed 10 grams per dose) orally every 6 hours for 20 doses, without regard to meals. See the full prescribing information for body surface area-based dosing. ( 2.1 ) Preparation and Administration Pediatric : Measure the dose using either a scale accurate to at least 0.1 gram, or a graduated teaspoon accurate to ¼ teaspoon. ( 2.1 ) Mix each VISTOGARD dose with 3 to 4 ounces of soft foods such as applesauce, pudding or yogurt and ingest within 30 minutes of mixing. Do not chew the VISTOGARD granules. Drink at least 4 ounces of water. ( 2.2 ) If a patient vomits within 2 hours of taking a dose of VISTOGARD, initiate another complete dose as soon as possible after the vomiting episode. Administer the next dose at the regularly scheduled time. ( 2.2 ) If a patient misses a dose at the scheduled time, administer that dose of VISTOGARD as soon as possible. Administer the next dose at the regularly scheduled time. ( 2.2 ) Administer VISTOGARD via a nasogastric tube (NG tube) or gastrostomy tube (G-Tube) when necessary (e.g., severe mucositis or coma). ( 2.2 ) 2.1 Recommended Dosage Adults: 10 grams (1 packet) orally every 6 hours for 20 doses, without regard to meals. Pediatric: 6.2 grams/m 2 of body surface area (not to exceed 10 grams per dose) orally every 6 hours for 20 doses, without regard to meals. The VISTOGARD dose to be administered at 6.2 grams/m 2 is presented in Table 1.

None. None. ( 5 )

Adverse reactions occurring in >2% of patients receiving VISTOGARD included vomiting, nausea, and diarrhea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact BTG International Inc at (1-877-377-3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions and using a wide range of doses, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of VISTOGARD was assessed in 135 patients (median age 59 years, 56% male) treated in 2 single-arm, open-label, multi-center trials. VISTOGARD was administered at 10 grams orally every 6 hours for 20 doses or at a body surface area adjusted dosage of 6.2 grams/m 2 /dose for 20 doses in four patients between 1 and 7 years of age. The median duration of exposure was 4.8 days, with a median of 20 doses (range 1 to 23). VISTOGARD was discontinued for adverse reactions in two (1.4%) patients. Serious adverse reactions and Grade ≥3 adverse reactions were seen in one patient receiving VISTOGARD (Grade 3 nausea and vomiting). Table 2 summarizes the adverse reactions that occurred in greater than 2% of patients in Studies 1 and 2 combined. Table 2 Adverse Reactions in > 2% of Patients Receiving VISTOGARD in Studies 1 and 2 Adverse Reaction N=135 Patients Vomiting 13 (10%) Nausea 7 (5%) Diarrhea 4 (3%)

8.1 Pregnancy Risk Summary Limited case reports of uridine triacetate use during pregnancy are insufficient to inform a drug-associated risk of birth defects and miscarriage. When administered orally to pregnant rats during the period of organogenesis, uridine triacetate at doses of one-half the maximum recommended human dose (MRHD) of 40 grams per day was not teratogenic and did not produce adverse effects on embryo-fetal development [see Data ] . The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, uridine triacetate was administered orally to pregnant rats during the period of organogenesis at doses up to 2000 mg/kg per day (about one-half the maximum recommended human dose (MRHD) of 40 grams per day on a body surface area basis). There was no evidence of teratogenicity or harm to the fetus and no effect on maternal body weight and overall health. 8.2 Lactation Risk Summary There are no data on the presence of uridine triacetate in human milk, the effect on the breastfed infant or the effect on milk production.

Metabolism

Absorption VISTOGARD delivers 4- to 6-fold more uridine into the systemic circulation compared to equimolar doses of uridine itself. Maximum concentrations of uridine in plasma following oral VISTOGARD are generally achieved within 2 to 3 hours, and the half-life ranges from approximately 2 to 2.5 hours.

• Sep 4, 2015NDANDA208169Btg Intl
• Dec 11, 2015NDANDA208159Btg Intl

1. 1Complication Associated With Device2216%
2. 2Diarrhoea2115%
3. 3Vomiting2115%
4. 4Off Label Use1612%
5. 5Thrombocytopenia139.4%
6. 6Mucosal Inflammation128.7%
7. 7Nausea128.7%
8. 8Neutropenia107.2%
9. 9Death96.5%
10. 10Hypokalaemia85.8%
11. 11Inappropriate Schedule Of Product Administration85.8%
12. 12Asthenia75.1%
13. 13Dysphagia64.3%
14. 14Product Dose Omission Issue64.3%
15. 15Decreased Appetite53.6%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Uridine Triacetate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Open-Label Study of Uridine Triacetate in Pediatric Patients With Hereditary Orotic Aciduria
  Completed · Phase 3 · Interventional · 4 enrolled · Wellstat Therapeutics
  NCT02110147updated 2017-07-31
• Uridine Triacetate as Antidote for Patients at Excess Risk of 5-FU Toxicity Due to Overdosage or Impaired Elimination
  Approved for marketing · Expanded access · Wellstat Therapeutics
  NCT01432301updated 2016-03-07
• Triacetyluridine and Fluorouracil Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced, or Metastatic Pancreatic Cancer
  Completed · Phase 3 · Interventional · 250 enrolled · Wellstat Therapeutics
  NCT00024427updated 2012-06-28
• S9915 Triacetyluridine, Fluorouracil, and Leucovorin in Treating Patients With Unresectable, Locally Advanced, or Metastatic Cancer of the Esophagus or Stomach
  Completed · Phase 2 · Interventional · 65 enrolled · SWOG Cancer Research Network
  NCT00004233updated 2011-07-25
• RG2133 (2',3',5'-Tri-O-Acetyluridine) in Mitochondrial Disease
  Terminated · Phase 1 · Interventional · 12 enrolled · Repligen Corporation
  NCT00060515updated 2005-08-05
• Phase I Study of PN401, Fluorouracil, Leucovorin and CPT-11 in Patients With Solid Tumors
  Terminated · Phase 1 · Interventional · 24 enrolled · Wellstat Therapeutics
  NCT00044785updated 2005-06-24

Frequently asked questions

How does Uridine Triacetate work?

Uridine triacetate is an acetylated pro-drug of uridine. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation.

What is Uridine Triacetate used for?

According to FDA labeling, Uridine Triacetate carries indications including: VISTOGARD ® is indicated for the emergency treatment of adult and pediatric patients: following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. VISTOGARD ® is a pyrimidine analog indicated for the emergency treatment of adult and pediatric patients: following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Uridine Triacetate?

Uridine Triacetate is classified as Various alimentary tract and metabolism products, Decreased Cellular Death, Increased DNA Integrity, Increased DNA Replication, Increased RNA Integrity.

What are the brand names for Uridine Triacetate?

Uridine Triacetate is marketed under brand names including Vistogard, Xuriden.

What are the contraindications for Uridine Triacetate?

Uridine Triacetate labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.