Effects of uridine triacetate: A Synthesis of Findings from 25 Studies

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Original Abstract of the Article

Main Research Findings

Uridine triacetate has been shown to be an effective treatment for overdose and early-onset severe toxicities from fluorouracil and capecitabine in a number of studies. 14 , 15 , 13 Fluorouracil and capecitabine are common chemotherapy drugs used to treat a variety of cancers, but they have a narrow therapeutic window and can cause serious side effects in some patients due to factors such as overdose or genetic predisposition. , 9 Uridine triacetate has also been shown to be effective in reducing toxicity from fluorouracil in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, an enzyme that plays a crucial role in the metabolism of fluorouracil. 10 , 8 A study found that uridine triacetate is effective within 96 hours of the last dose of fluorouracil or capecitabine. 3 , 4

Benefits and Risks

Benefit Summary

Uridine triacetate is an effective treatment for overdose and early-onset severe toxicities from fluorouracil and capecitabine. 14 , 15 , 13 A study found that uridine triacetate is effective within 96 hours of the last dose of fluorouracil or capecitabine. 3 , 4 Uridine triacetate has also been shown to be effective in reducing toxicity from fluorouracil in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. 10 , 8

Risk Summary

Uridine triacetate may cause side effects such as vomiting, nausea, and diarrhea. 14 The effectiveness and safety of uridine triacetate have not been established if it is administered more than 96 hours after the last dose of fluorouracil or capecitabine. 14 Uridine triacetate is not recommended for the treatment of non-emergent adverse reactions associated with fluorouracil or capecitabine. 14 Uridine triacetate may diminish the efficacy of fluorouracil or capecitabine. 14

Study Comparisons

Study Commonalities

Multiple studies have shown that uridine triacetate is an effective treatment for overdose and early-onset severe toxicities from fluorouracil and capecitabine. 14 , 15 , 13 , 3 , 4 These studies also shared a concern that uridine triacetate may reduce the efficacy of fluorouracil or capecitabine. 14

Study Differences

The effectiveness of uridine triacetate may vary between studies. 10 , 8 The timing and duration of uridine triacetate administration may also differ between studies. 14 Additionally, the side effects of uridine triacetate may vary between studies. 14

Consistency and Contradictions in Results

Multiple studies have shown that uridine triacetate is an effective treatment for overdose and early-onset severe toxicities from fluorouracil and capecitabine. 14 , 15 , 13 , 3 , 4 However, the effectiveness of uridine triacetate may vary between studies. 10 , 8 The timing and duration of uridine triacetate administration may also differ between studies. 14 Additionally, the side effects of uridine triacetate may vary between studies. 14

Cautionary Notes Regarding Real-World Applications

Uridine triacetate is being used in medical practice as a potentially effective treatment for overdose and early-onset severe toxicities from fluorouracil and capecitabine. 14 , 15 , 13 However, uridine triacetate may reduce the efficacy of fluorouracil or capecitabine. 14 Additionally, the effectiveness and safety of uridine triacetate have not been established if it is administered more than 96 hours after the last dose of fluorouracil or capecitabine. 14 Therefore, the use of uridine triacetate should be guided by a medical professional.

Current Research Limitations

There is still not enough research on uridine triacetate. 10 , 8 Further research is needed to assess the effectiveness and safety of uridine triacetate. 14 More data is also needed on the long-term effects of uridine triacetate. 14

Future Research Directions

Large-scale clinical trials are needed to further investigate the effectiveness and safety of uridine triacetate. 14 Studies are also needed to evaluate the long-term effects of uridine triacetate. 14 In addition, research is needed to assess the combined effects of uridine triacetate with other therapies. 14

Conclusion

Uridine triacetate is a promising treatment for overdose and early-onset severe toxicities from fluorouracil and capecitabine. 14 , 15 , 13 However, more research is needed to evaluate its effectiveness and safety. 14 The use of uridine triacetate should be guided by a medical professional.

Literature analysis of 25 papers
Positive Content
21
Neutral Content
2
Negative Content
2
Article Type
1
0
0
5
22
1.

Verteporfin: new indication. New indication in complications of high myopia: no sustained benefit.

Author:

Stabilize vision
Limited efficacy

High myopia can lead to subfoveal choroidal neovascularisation, causing a significant loss of central vision. Verteporfin, a drug that received marketing authorisation, may be helpful in stabilizing visual acuity for one year, but this advantage is lost after two years.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Two patients with fluoropyrimidine overdose successfully managed without uridine triacetate.

Author: KatsChantal Jar, JochemsAnouk, JeurissenFrank Jf, LedeboerAletta, van den BergRoland B

5-FU overdose

This case report describes two patients who experienced 5-fluorouracil overdose due to unintentional increased infusion rates. It highlights the rationale for avoiding uridine triacetate treatment in such cases.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Oral Capecitabine Exposures and Use of Uridine Triacetate: A 20-Year Retrospective Analysis.

Author: SeltzerJustin A, FriedmanNathan A, HardinJeremy, GalustHenrik, CantrellF Lee, MinnsAlicia

Capecitabine overdose antidote
Capecitabine toxicity

Capecitabine, a prodrug of 5-fluorouracil, can cause toxicity. This study characterized accidental and intentional capecitabine exposures and the use of uridine triacetate as an antidote.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Reversible Toxic Encephalopathy Involving the Cerebellum and Subcortical White Matter Attributed to Capecitabine.

Author: LiYongchang, WuXiaomei, ZhongWei, TangXiangqi

Cancer treatment
Toxic encephalopathy

Capecitabine is an anticancer drug that can cause central nervous system toxicity. This report describes a rare case of capecitabine-related toxic encephalopathy involving the cerebellum and subcortical white matter.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?

Author: LampropoulouDimitra Ioanna, LaschosKonstantinos, AmylidiAnna-Lea, AngelakiAriadni, SouposNikolaos, BoumpoucheropoulosSotirios, PapadopoulouEirini, NanouEvgenia, ZidianakisVasilios, NasioulasGeorge, FildissisGeorge, AravantinosGerasimos

Capecitabine toxicity treatment
Drug access

This report highlights the difficulty in accessing uridine triacetate, an FDA-approved antidote for 5-fluorouracil or capecitabine overdose, for Greek patients due to time restrictions in the summary of product characteristics. The case involved a patient with heterozygous dihydropyrimidine dehydrogenase deficiency who experienced capecitabine toxicity.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Capecitabine-induced cerebellar toxicity and TYMS pharmacogenetics.

Author: SaifMuhammad W

Breast cancer treatment
Colorectal cancer treatment
Cerebellar syndrome
Multifocal leukoencephalopathy
Neurotoxicity
Peripheral neuropathy

Capecitabine neurotoxicity may be linked to TYMS polymorphism, suggesting a potential role for pharmacogenetics in managing this adverse effect and optimizing treatment strategies for cancer patients.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Uridine triacetate for severe 5-fluorouracil toxicity in a patient with thymidylate synthase gene variation: Potential pharmacogenomic implications.

Author: BaldeoCandice, VishnuPrakash, ModyKabir, KasiPashtoon Murtaza

5-FU toxicity treatment
5-FU toxicity

Pharmacogenomic testing can help identify patients at risk for 5-fluorouracil toxicity. This case report suggests that uridine triacetate may be effective even beyond the recommended 96 hours in patients with thymidylate synthase gene variations.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

9.

Fluoropyrimidine-induced cardiotoxicity.

Author: DepetrisIlaria, MarinoDonatella, BonzanoAlessandro, CagnazzoCeleste, FilippiRoberto, AgliettaMassimo, LeoneFrancesco

Cardiotoxicity

Fluoropyrimidines (5-fluorouracil and capecitabine) are antimetabolite drugs used for cancer treatment. This review summarizes the current state of knowledge on fluoropyrimidine-induced cardiotoxicity (FIC), a rare but potentially life-threatening toxicity. It explores the pathogenetic models, risk factors, detection methods, and treatment options, including uridine triacetate.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

10.

Successful use of uridine triacetate (Vistogard) three weeks after capecitabine in a patient with homozygous dihydropyrimidine dehydrogenase mutation: A case report and review of the literature.

Author: ZuraykMira, KeungYi-Kong, YuDavid, HuEddie Hl

Uridine triacetate
Capecitabine toxicity

Fluorouracil and capecitabine are cancer drugs that can cause serious side effects. Uridine triacetate is a drug used to treat side effects from these drugs. This study describes a case of a patient who did not respond to treatment with uridine triacetate.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Case report of capecitabine toxicity and use of uridine triacetate.

Author: OliverWesley D, DuffyAlison P, HausnerPetr F

Fluorouracil and capecitabine toxicity treatment
Toxicity treatment failure

Fluorouracil and capecitabine are cancer drugs that can cause serious side effects. Uridine triacetate is a drug used to treat side effects from these drugs. This study describes a case of a patient who did not respond to treatment with uridine triacetate.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

Early-Onset 5-Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate.

Author: VaudoChristine E, GilBrigitte, GaluskiKari, ZarwanCorrine, NugentFrancis W

5-FU toxicity reversal

This case report describes a 73-year-old man with anal cancer who developed severe 5-fluorouracil (5-FU) toxicity despite being negative for dihydropyrimidine dehydrogenase (DPD) mutations. Treatment with uridine triacetate, an antidote for 5-FU toxicity, resulted in recovery of the patient's neutrophil count and improvement in mucositis.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

13.

Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity.

Author: MaWen Wee, SaifMuhammad Wasif, El-RayesBassel F, FakihMarwan G, CartwrightThomas H, PoseyJames A, KingThomas R, von BorstelReid W, BamatMichael K

5-FU toxicity treatment

Uridine triacetate (Vistogard) was approved in 2015 for adult and pediatric patients who exhibit early-onset severe or life-threatening 5-FU/capecitabine toxicities or present with an overdose. Uridine triacetate delivers high concentrations of uridine, which competes with toxic 5-FU metabolites.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

FDA Approval: Uridine Triacetate for the Treatment of Patients Following Fluorouracil or Capecitabine Overdose or Exhibiting Early-Onset Severe Toxicities Following Administration of These Drugs.

Author: IsonGwynn, BeaverJulia A, McGuinnW David, PalmbyTodd R, DininJeannette, CharlabRosane, MaratheAnshu, JinRunyan, LiuQi, ChenXiao Hong, YsernXavier, StephensOlen, BaiGe, WangYaning, DorffSarah E, ChengJoyce, TangShenghui, SridharaRajeshwari, PierceWilliam, McKeeAmy E, IbrahimAmna, KimGeoffrey, PazdurRichard

Fluorouracil/capecitabine overdose treatment
Diarrhea
Gastrointestinal toxicity
Nausea

Uridine triacetate (VISTOGARD) is now approved for emergency treatment of fluorouracil or capecitabine overdose. The drug is effective in reducing severe toxicity and increasing survival in patients with fluorouracil or capecitabine overdose.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

Benefit of uridine triacetate (Vistogard) in rescuing severe 5-fluorouracil toxicity in patients with dihydropyrimidine dehydrogenase (DPYD) deficiency.

Author: SaifMuhammad Wasif, DiasioRobert B

5-FU toxicity reduction

This study investigated the potential of uridine triacetate (Vistogard) as an antidote for 5-FU poisoning in humans with dihydropyrimidine dehydrogenase (DPYD) deficiency.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Use of uridine triacetate for the management of fluorouracil overdose.

Author: McEvillyMargaret, PopelasCarl, TremmelBob

Fluorouracil overdose treatment

Uridine triacetate effectively treated a patient who received a fluorouracil overdose. The patient received oral uridine triacetate for five days without experiencing nausea or vomiting. This highlights the potential of uridine triacetate to manage fluorouracil toxicity.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Enhanced uridine bioavailability following administration of a triacetyluridine-rich nutritional supplement.

Author: WeinbergMelissa E, RomanMark C, JacobPeyton, WenMichael, CheungPolly, WalkerUlrich A, MulliganKathleen, SchambelanMorris

Mitochondrial dysfunction treatment
Orotic aciduria treatment

This study investigates the use of uridine as a therapy for hereditary orotic aciduria and other mitochondrial dysfunction disorders, including HIV-related toxicities. A food supplement containing nucleosides, NucleomaxX®, was found to increase plasma uridine levels to supraphysiologic levels, potentially improving uridine's bioavailability.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

19.

Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients.

Author: JensenJ Eric, DanielsMelissa, HawsCharlotte, BoloNicolas R, LyooIn Kyoon, YoonSujung J, CohenBruce M, StollAndrew L, RuscheJames R, RenshawPerry F

Depression treatment

Triacetyluridine (TAU) is a drug that is being investigated for the treatment of depression. This study found that TAU may improve symptoms of depression and improve mitochondrial function.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's disease.

Author: SaydoffJoel A, GarciaRolando A G, BrowneSusan E, LiuLiansheng, ShengJin, BrennemanDenise, HuZhongyi, CardinSylvain, GonzalezAlexis, von BorstelReid W, GregorioJason, BurrHolly, BealM Flint

HD treatment

PN401, a uridine pro-drug, was found to be protective in mouse models of Huntington's disease (HD). It increased survival and improved motor function, decreased neurodegeneration, and increased cortical BDNF levels.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

21.

Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a Southwest Oncology Group study.

Author: DoroshowJames H, McCoySheryl, MacdonaldJohn S, IssellBrian F, PatelTaral, CobbPatrick W, YostKathleen J, AbbruzzeseJames L

Gastric adenocarcinoma treatment
Gastrointestinal toxicity
Hematologic toxicity

A phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401 in patients with advanced gastric adenocarcinoma showed acceptable toxicity and a median survival of 7.2 months.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

24.

Neuroprotective effects of oral administration of triacetyluridine against MPTP neurotoxicity.

Author: KlivenyiPeter, GardianGabrielle, CalingasanNoel Y, YangLichuan, von BorstelReid, SaydoffJoel, BrowneSusan E, BealM Flint

Attenuated dopamine depletion
Neuroprotective effects
Reduced neuronal loss

Triacetyluridine (TAU) is a drug that delivers pyrimidines to the brain, which may help to compensate for bioenergetic defects. Studies show that TAU may be a novel approach for treating neurodegenerative diseases, such as Parkinson’s disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

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