uridine triacetate

Uridine triacetate is a medication used to treat hereditary orotic aciduria, a rare genetic disorder, and for the emergency treatment of overdose or toxicity from the treatment of cancer with chemotherapy drugs fluorouracil or capecitabine. Uridine triacetate is a manufactured form of a naturally occurring enzyme uridine monophosphate that performs essential functions in the synthesis of DNA and RNA. Uridine triacetate is administered as oral granules.

Hereditary orotic aciduria is caused by mutations in the uridine monophosphate synthetase (UMPS) gene, which impair the body’s ability to synthesize adequate uridine. Uridine is essential for the conversion of orotic acid, another chemical substance in the body, into pyrimidine nucleotide, a compound that is one of the building blocks of DNA and RNA. Uridine deficiency causes reduced pyrimidine nucleotide synthesis, and urinary excretion of orotic acid. Uridine triacetate is a replacement therapy that compensates for natural uridine deficiency.

Fluorouracil is a pyrimidine analog that has a structure similar to pyrimidine and capecitabine is converted to fluorouracil in the body. In the treatment of cancer, the active metabolites of fluorouracil get incorporated into the DNA and RNA in place of pyrimidine, damaging and destroying the cancer cells. Fluorouracil, however, affects both cancer and normal cells which results in toxicity and multiple adverse effects. Uridine triacetate competes with one of the active metabolites of fluorouracil and inhibits cell damage and death caused by fluorouracil.

The FDA-approved uses of uridine triacetate are:

• Treatment of hereditary orotic aciduria in adults and children
• Emergency treatment of adults and pediatric patients:
  • following a fluorouracil or capecitabine overdose regardless of the presence of symptoms
  • who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (for example, gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration

Limitations of use

• Uridine triacetate is not recommended for nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs.
• Safety and efficacy of uridine triacetate initiated more than 96 hours following the end of fluorouracil or capecitabine administration have not been established.

No side effects were reported with the use of uridine triacetate in the treatment of hereditary orotic aciduria.

Common side effects of uridine triacetate in the treatment of fluorouracil or capecitabine overdose/toxicity include:

• Vomiting
• Nausea
• Diarrhea

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Oral granules

• 2 g/packet (Xuriden)
• 10 g/packet (Vistogard)

Adult:

Hereditary Orotic Aciduria

60 mg/kg orally once daily mixed with milk; increase dose to 120 mg/kg (not to exceed 8 g) once daily for insufficient efficacy as follows:

• Levels of orotic acid in urine remain above normal or increase above the usual or expected range for patient
• Laboratory values (e.g., red blood cell or white blood cell indices) affected by hereditary orotic aciduria show evidence of worsening
• Worsening of other signs or symptoms of the disease
• Total daily dose by weight category below was rounded to achieve approximate dose level (2 g = 3/4 tsp)

Total daily dose by weight category below rounded to achieve approximate dose level at the 120-mg/kg dose level

• 41-45 kg: 2.5-2.7 g (1 tsp)
• 46-50 kg: 2.8-3 g (1 tsp)
• 51-55 kg: 3.1-3.3 g (1.25 tsp)
• 56-60 kg: 3.4-3.6 g (1.25 tsp)
• 61-65 kg: 3.7-3.9 g (1.5 tsp; may use 2 entire 2-g packets without weighing or measuring)
• 66-70 kg: 4-4.2g (1.5 tsp; may use 2 entire 2-g packets without weighing or measuring)
• 71-75 kg: 4.3-4.5g (1.5 tsp; may use 2 entire 2-g packets without weighing or measuring)
• Above 75 kg: 6 g (2 tsp; may use 3 entire 2-g packets without weighing or measuring)

Total daily dose by weight category below rounded to achieve approximate dose level at the 120-mg/kg dose level

• 41-45 kg: 5-5.4 g (2 tsp; may use 3 entire 2-g packets without weighing or measuring)
• 46-50 kg: 5.6–6 g (2 tsp; may use 3 entire 2-g packets without weighing or measuring)
• 51-55 kg: 6.2-6.6 g (2.5 tsp)
• 56-60 kg: 6.8-7.2 g (2.5 tsp)
• 61-65 kg: 7.4-7.8 g (2.5 tsp)
• 66-70 kg: 8 g (2.75 tsp; may use 4 entire 2-g packets without weighing or measuring)

Fluorouracil or Capecitabine Overdose or Severe Toxicity

Dose

• Adults: 10 g (1 packet) orally once every 6 hours for 20 doses
• May take without regard to meals

Pediatric:

Hereditary Orotic Aciduria

60 mg/kg orally once daily mixed with milk/infant formula; increase dose to 120 mg/kg (not to exceed 8 g) once daily for insufficient efficacy as follows:

• Levels of orotic acid in urine remain above normal or increase above the usual or expected range for patient
• Laboratory values (e.g., red blood cell or white blood cell indices) affected by hereditary orotic aciduria show evidence of worsening
• Worsening of other signs or symptoms of the disease
• Total daily dose by weight category below was rounded to achieve approximate dose level (2 g = 3/4 tsp)

Total daily dose by weight category below rounded to achieve approximate dose level at the 60 mg/kg dose level

• 5 kg and above: 0.4 g (1/8 tsp)
• 6-10 kg: 0.4-0.6 g (1/4 tsp)
• 11-15 kg: 0.7-0.9 g (1/2 tsp)
• 16-20 kg: 1-1.2 g (1/2 tsp)
• 21-25 kg: 1.3-1.5 g (1/2 tsp)
• 26-30 kg: 1.6-1.8 g (3/4 tsp; may use 1 entire 2-g packet without weighing or measuring)
• 31-35 kg: 1.9-2.1 g (3/4 tsp; may use 1 entire 2-g packet without weighing or measuring)
• 36-40 kg: 2.2-2.4 g (1 tsp)
• 41-45 kg: 2.5-2.7 g (1 tsp)
• 46-50 kg: 2.8-3 g (1 tsp)
• 51-55 kg: 3.1-3.3 g (1.25 tsp)
• 56-60 kg: 3.4-3.6 g (1.25 tsp)
• 61-65 kg: 3.7-3.9 g (1.5 tsp)
• 66-70 kg: 4.3-4.5 g (1.5 tsp)
• Above 70 kg: 6 g (2 tsp; may use 3 entire 2-g packets without weighing or measuring)

Total daily dose by weight category below rounded to achieve approximate dose level at the 120 mg/kg dose level

• 5 kg and above: 0.8 g (1/4 tsp)
• 6-10 kg: 0.8-1.2 g (1/2 tsp)
• 11-15 kg: 1.4-1.8 g (3/4 tsp)
• 16-20 kg: 2-2.4 g (1 tsp)
• 21-25 kg: 2.6-3 g (1 tsp)
• 26-30 kg: 3.2-3.6 g (1.25 tsp)
• 31-35 kg: 3.8-4.2 g (1.5 tsp; may use 2 entire 2-g packets without weighing or measuring)
• 36-40 kg: 4.4-4.8 g (1.75 tsp)
• 41-45 kg: 5-5.4 g (2 tsp; may use 3 entire 2-g packets without weighing or measuring)
• 46-50 kg: 5.6-6 g (2 tsp; may use 3 entire 2-g packets without weighing or measuring)
• 51-55 kg: 6.2-6.6 g (2/25 tsp)
• 56-60 kg: 6.8-7/2 g (2.5 tsp)
• 61-65 kg: 7.4-7.8 g (2.5 tsp)
• 66 kg and above: 8 g (2.75 tsp; may use 4 entire 2-g packets without weighing or measuring)

Fluorouracil or Capecitabine Overdose or Severe Toxicity

Dose

• 6.2 g/m² orally once every 6 hours for 20 doses; not to exceed 10 g/dose
• May take without regard to meals
• Total daily dose by body surface area rounded to achieve approximate dose
  • 0.34-0.44 m²: 2.1-.27 g (1 tsp)
  • 0.45-0.55 m²: 2.8-34 g (1.25 tsp)
  • 0.56-0.66 m²: 3.5-4.1 g (1.5 tsp)
  • 0.67-0.77 m²: 4.2-4.8 g (1.75 tsp)
  • 0.78-0.88 m²: 4.9-5.4 g (2 tsp)
  • 0.89-0.99 m²: 5.5-6.1 g (2.25 tsp)
  • m²: 6.2-6.8 g (2.5 tsp)
  • 1.11 to 1.21 m²: 6.9-7.5 g (2.75 tsp)
  • 1.22-1.32 m²: 7.6-8/1 g (3 tsp)
  • 1.33-1.43 m²: 8.2-8.8 g (3.25 tsp)
  • 1.44 m² and above: 10 g (1 full packet)

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Uridine triacetate has no listed severe, serious, moderate, or mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no data available on the use of uridine triacetate in pregnant women to identify a drug-associated risk of major birth defects or miscarriage. Animal studies with uridine triacetate administration during pregnancy did not show evidence of any adverse effects on embryo-fetal development.
• There is no information on the presence of uridine triacetate in breastmilk or its effects on milk production or the breastfed infant. Decision to breastfeed should be based on the nursing mother’s clinical need for uridine triacetate, health and developmental benefits of breastfeeding, and the risks to the breastfed infant from exposure to the drug or the mother’s underlying condition.

• Take uridine triacetate oral granules exactly as prescribed. Follow all administration instructions and complete the prescribed course of treatment.
• Store uridine triacetate safely out of reach of children.
• There is no information available on the overdose of uridine triacetate. In case of overdose, report to your treating physician.