Xuriden
Xuriden Uses, Dosage, Side Effects, Food Interaction and all others data.
Xuriden, formerly known as vistonuridine, is an orally active prodrug of the naturally occurring nucleoside uridine. It is used for the treatment of hereditary orotic aciduria (Xuriden), or for the emergency treatment of fluorouracil or capecitabine overdose or toxicity (Vistogard). It is provided in the prodrug form as uridine triacetate as this form delivers 4- to 6-fold more uridine into the systemic circulation compared to equimolar doses of uridine itself.
When used for the treatment or prevention of toxicity associated with fluorouracil and other antimetabolites, uridine triacetate is utilized for its ability to compete with 5-fluorouracil (5-FU) metabolites for incorporation into the genetic material of non-cancerous cells. It reduces toxicity and cell-death associated with two cytotoxic intermediates: 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). Normally, FdUMP inhibits thymidylate synthase required for thymidine synthesis and DNA replication and repair while FUTP incorporates into RNA resulting in defective strands. As a result, these metabolites are associated with various unpleasant side effects such as neutropenia, mucositis, diarrhea, and hand–foot syndrome. Like many other neoplastic agents, these side effects limit the doses of 5-FU that can be administered, which also affects the efficacy for treatment. By pre-administering with uridine (as the prodrug uridine triacetate), higher doses of 5-FU can be given allowing for improved efficacy and a reduction in toxic side effects . It can also be used as a rescue therapy if severe side effects present within 96 hours after initiation of therapy.
Xuriden is also used for the treatment of hereditary orotic aciduria, also known as uridine monophosphate synthase deficiency. This rare congenital autosomal recessive disorder of pyrimidine metabolism is caused by a defect in uridine monophosphate synthase (UMPS), a bifunctional enzyme that catalyzes the final two steps of the de novo pyrimidine biosynthetic pathway. As a result of UMPS deficiency, patients experience a systemic deficiency of pyrimidine nucleotides, accounting for most symptoms of the disease. Additionally, orotic acid from the de novo pyrimidine pathway that cannot be converted to UMP is excreted in the urine, accounting for the common name of the disorder, orotic aciduria. Furthermore, orotic acid crystals in the urine can cause episodes of obstructive uropathy. When administered as the prodrug uridine triacetate, uridine can be used by essentially all cells to make uridine nucleotides, which compensates for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced.
Trade Name | Xuriden |
Generic | Uridine triacetate |
Uridine triacetate Other Names | 2',3',5'-Triacetyluridine, Tri-O-acetyluridine, Triacetyl uridine, Triacetyluridine, Uridine triacetate, Vistonuridine |
Weight | 10g, |
Type | Oral Granule, Oral |
Formula | C15H18N2O9 |
Weight | Average: 370.314 Monoisotopic: 370.101230168 |
Groups | Approved, Investigational |
Therapeutic Class | |
Manufacturer | |
Available Country | United States, |
Last Updated: | September 19, 2023 at 7:00 am |
Uses
Xuriden is a pyrimidine analog used for the reversal of overdose, regardless of the presence of symptoms, and early-onset, severe or life-threatening CNS toxicity or cardiotoxicity of fluorouracil or capecitabine.
Marketed as the product Xuriden (FDA), uridine triacetate is indicated for the treatment of hereditary orotic aciduria.
Marketed as the product Vistogard (FDA), uridine triacetate is indicated for the emergency treatment of adult and pediatric patients in the following situations: 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.
Xuriden is also used to associated treatment for these conditions: Orotic aciduria, Capecitabine overdose, Fluorouracil overdose
How Xuriden works
Xuriden is a synthetic uridine pro-drug that is converted to uridine in vivo. When used for the treatment or prevention of toxicity associated with fluorouracil and other antimetabolites, uridine triacetate is utilized for its ability to compete with 5-fluorouracil (5-FU) metabolites for incorporation into the genetic material of non-cancerous cells. It reduces toxicity and cell-death associated with two cytotoxic intermediates: 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). By pre-administering with uridine (as the prodrug uridine triacetate), higher doses of 5-FU can be given allowing for improved efficacy and a reduction in toxic side effects such as neutropenia, mucositis, diarrhea, and hand–foot syndrome.
Xuriden is also used for replacement therapy in the treatment of hereditary orotic aciduria, also known as uridine monophosphate synthase (UMPS) deficiency. As a result of UMPS deficiency, patients experience a systemic deficiency of pyrimidine nucleotides, accounting for most symptoms of the disease. Additionally, orotic acid from the de novo pyrimidine pathway that cannot be converted to UMP is excreted in the urine, accounting for the common name of the disorder, orotic aciduria. Furthermore, orotic acid crystals in the urine can cause episodes of obstructive uropathy. When administered as the prodrug uridine triacetate, uridine can be used by essentially all cells to make uridine nucleotides, which compensates for the genetic deficiency in synthesis in patients with hereditary orotic aciduria.
Food Interaction
- Take with a full glass of water. Take with at least 4 ounces of water.
- Take with or without food. Mix the uridine triacetate granules with soft food and consume within 30 minutes of mixing.
Volume of Distribution
Circulating uridine is taken up into mammalian cells via specific nucleoside transporters, and also crosses the blood brain barrier.
Elimination Route
Maximum concentrations of uridine in plasma following oral administration are generally achieved within 2 to 3 hours.
Half Life
2 to 2.5 hours
Elimination Route
Uridine can be excreted via the kidneys, but is also metabolized by normal pyrimidine catabolic pathways present in most tissues.
Innovators Monograph
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