Uridine Triacetate

Pregnancy: There are no available data in pregnant women to determine a drug-associated risk; when administered orally to pregnant rats during period of organogenesis, uridine triacetate at doses similar to maximum recommended human dose (MRHD) of 120 mg/kg/day was not teratogenic and did not produce adverse effects on embryo-fetal development

Lactation: There are no data on presence of uridine triacetate in human milk, effect on the breastfed infant, or effect on milk production; development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the therapy and any potential adverse effects on breastfed infant from the therapy or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Uridine triacetate comes as granules to take by mouth. It is usually taken with or without meals four times a day (every 6 hours) for 20 doses. Take uridine triacetate at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take uridine triacetate exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Mix the granules into 3 to 4 ounces (9 to 120 grams) of a soft food such as applesauce, pudding, or yogurt. Take the mixture right away (within 30 minutes of mixing the granules with food) without chewing the granules and then drink at least 4 ounces (120 mL) of water to make sure that you swallow all of the medication.

If you are preparing a dose for a child, measure the dose using measuring teaspoons (accurate to 1/4 teaspoon) or a scale (accurate to at least 0.1 gram). Dispose of any remaining granules; do not use granules left in the packet for your next doses.

If you vomit within 2 hours of taking a dose, take another full dose as soon as possible after the vomiting episode and then take your next dose at the regularly scheduled time.

Uridine triacetate granules can be given through certain types of feeding tubes. If you have a feeding tube, ask your doctor how you should take the medication. Follow the directions carefully.

It is important that you take all 20 doses of uridine triacetate, even if you feel well. Do not stop taking uridine triacetate without talking to your doctor.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that use the p-glycoprotein transporter such as digoxin (Lanoxin), loperamide (Imodium), quinidine, vinblastine (Velban), fexofenadine (Allegra), indinavir (Crixivan), colchicine (Colcrys),topotecan (Hycamtin), and paclitaxel (Abraxane, Onxol, Taxol)

This is not a complete list of uridine triacetate drug interactions. Ask your doctor or pharmacist for more information.

Do not take uridine triacetate if you are allergic to uridine triacetate or any of its ingredients. 

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Usual Adult Dose for Fluorouracil/Capecitabine Overdose:

10 grams (1 packet) orally every 6 hours for 20 doses

Comments: Each dose should be mixed with 3 to 4 ounces of soft foods such as applesauce, pudding, or yogurt, and ingested within 30 minutes along with 4 ounces of water.

Use: Emergency treatment of a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or for patients 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.

Usual Adult Dose for Orotic Aciduria:

Initial Dose: 60 mg/kg orally once a day

Maintenance Dose: Increase dosage to 120 mg/kg orally once a day for insufficient efficacy, such as occurrence of one of the following:
-levels of orotic acid in urine remain above normal or increase above the usual or expected range for the 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.

Maximum Dose: 8 grams orally once a day

Comments: For patients requiring doses in multiples of 2 grams (3/4 teaspoon), an entire drug packet(s) may be administered without weighing or measuring.

Use: Treatment of hereditary orotic aciduria

Usual Pediatric Dose for Fluorouracil/Capecitabine Overdose:

6.2 grams/m2 BSA orally every 6 hours for 20 doses

Maximum Dose: 10 grams per dose

Comments:
-Measure the dose using either a scale accurate to at least 0.1 gram, or a graduated teaspoon accurate to 1/4 teaspoon.
-Each dose should be mixed with 3 to 4 ounces of soft foods such as applesauce, pudding, or yogurt, and ingested within 30 minutes along with 4 ounces of water.
-Unused granules should be discarded and not used for subsequent dosing.
-Limited clinical data indicates response and safety are similar in pediatric and adult patients.

Use: Emergency treatment of a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or for patients 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.

Usual Pediatric Dose for Orotic Aciduria:

Initial Dose: 60 mg/kg orally once a day

Maintenance Dose: Increase dosage to 120 mg/kg orally once a day for insufficient efficacy, such as occurrence of one of the following:
-levels of orotic acid in urine remain above normal or increase above the usual or expected range for the 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.

Maximum Dose: 8 grams orally once a day

Comments:
-This drug can be mixed with milk or infant formula for patients receiving up to 2 grams (3/4 teaspoon); the manufacturer product information should be consulted for administration instructions.
-For patients requiring doses in multiples of 2 grams (3/4 teaspoon), an entire drug packet(s) may be administered without weighing or measuring.

Use: Treatment of hereditary orotic aciduria

6.2 grams/m2 BSA orally every 6 hours for 20 doses

Maximum Dose: 10 grams per dose

Comments:
-Measure the dose using either a scale accurate to at least 0.1 gram, or a graduated teaspoon accurate to 1/4 teaspoon.
-Each dose should be mixed with 3 to 4 ounces of soft foods such as applesauce, pudding, or yogurt, and ingested within 30 minutes along with 4 ounces of water.
-Unused granules should be discarded and not used for subsequent dosing.
-Limited clinical data indicates response and safety are similar in pediatric and adult patients.

Use: Emergency treatment of a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or for patients 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.

Administration Advice:
-This drug should be administered as soon as possible after a fluorouracil or capecitabine overdose.
-If a patient vomits within 2 hours of a dose or misses a dose, another complete dose should be initiated as soon as possible and the next dose should be administered at the regularly scheduled time.
-This drug can be taken with or without food.
-The drug granules should not be chewed.
-This drug can be mixed with 3 to 4 ounces of applesauce, pudding, or yogurt and it also may be administered via a nasogastric tube or gastrostomy tube when necessary (e.g., coma, severe mucositis); the manufacturer product information should be consulted for administration instructions.

Storage Requirements:
-This drug should be stored at 25 degrees Celsius (77 Fahrenheit); excursions permitted to 15 to 30 degrees Celsius (59 to 86 Fahrenheit).

Preparation Techniques:
-Consult the manufacturer product information for preparation information.
-Discard any unused drug granules.

General:
-There are no apparent differences in clinical response between adults and pediatric patients with hereditary orotic aciduria treated with uridine; however, data are limited.
-Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger subjects.
-This drug is not recommended for non-emergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs.
-The safety and efficacy of this drug initiated more than 96 hours following the end of fluorouracil or capecitabine administration have not been established.
-Animal studies show this drug diminishes hematological toxicity and damage to the intestinal mucosa caused by fluorouracil treatment.

Patient Advice:
-Take the full treatment course even if you feel well.

Acetylated prodrug of uridine and a pyrimidine analog; a direct biochemical fluorouracil antagonist and a uridine replacement agent.1 3 9 10

Uridine triacetate and uridine do not inhibit CYP isoenzymes 3A4, 1A2, 2C8, 2C9, 2C19, 2D6, or 2E1.1 3 Neither uridine triacetate nor uridine induces CYP isoenzymes 1A2, 2B6, or 3A4.1 3

Weak substrate for P-glycoprotein (P-gp).1 3 6

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Clinically important interactions with inhibitors or inducers of CYP isoenzymes unlikely.1 3 14

Drugs Affecting or Affected by the P-glycoprotein Transport System

Substrates of P-gp: Potential pharmacokinetic interaction with orally administered P-gp substrates.1 3

Specific Drugs