Difference between revisions of "Fluorouracil (5-FU)"

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Also known as Adrucil.
 
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==General information==
 
==General information==
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Class/mechanism: Pyrimidine analog, antimetabolite, inhibitor of thymidylate synthase. Metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis by binding to thymidylate synthase and inhibiting production of thymidylate; FUTP interferes with RNA processing when it is mistakenly incorporated in place of uridine triphosphate (UTP).<ref name="insert">[http://patient.cancerconsultants.com/druginserts/Fluorouracil.pdf Fluorouracil (5-FU) package insert]</ref><ref>[http://hemonc.org/docs/packageinsert/fluorouracil.pdf Fluorouracil (5-FU) package insert (locally hosted backup)]</ref> <ref>[http://en.wikipedia.org/wiki/Fluorouracil#Interactive_pathway_map 5-FU pathway]</ref>.
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Class/mechanism: Pyrimidine analog, antimetabolite, inhibitor of thymidylate synthase. Metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis by binding to thymidylate synthase and inhibiting production of thymidylate; FUTP interferes with RNA processing when it is mistakenly incorporated in place of uridine triphosphate (UTP).<ref name="insert">[[:File:fluorouracil.pdf | Fluorouracil (5-FU) package insert (locally hosted backup)]]</ref><ref>[https://en.wikipedia.org/wiki/Fluorouracil#Interactive_pathway_map 5-FU pathway]</ref>.
 
<br>Route: IV
 
<br>Route: IV
 
<br>Extravasation: [[irritant]]
 
<br>Extravasation: [[irritant]]
  
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>  
+
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [https://online.lexi.com/lco/action/login UpToDate Lexidrug], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>  
 +
 
 +
==Patient safety==
 +
DPYD intermediate or poor metabolizers: Results in higher adverse reaction risk (severe, life-threatening, or fatal toxicities). No dosage has proven safe in poor metabolizers, and insufficient data are available to recommend a dosage in intermediate metabolizers. Withhold or discontinue in the presence of early-onset or unusually severe toxicity.<ref>[https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations]</ref>
 +
 
 +
EMA has recommended that patients should be tested for the lack of the enzyme dihydropyrimidine dehydrogenase (DPD) before starting cancer treatment with fluorouracil given by injection or infusion (drip) or with the related medicines, capecitabine and tegafur.
 +
 
 +
===References===
 +
#Delaunoit T, Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Findlay BP, Thomas SP, Salim M, Schaefer PL, Stella PJ, Green E, Mailliard JA. Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup Trial N9741. Cancer. 2004 Nov 15;101(10):2170-6. [https://doi.org/10.1002/cncr.20594 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15470715/ PubMed]
 +
 
 +
==Diseases for which it is established ''(work in progress)''==
 +
*[[Hepatocellular carcinoma]]
 +
*[[Nasopharyngeal carcinoma]]
  
 
==Diseases for which it is used==
 
==Diseases for which it is used==
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*[[Bladder cancer]]
 
*[[Bladder cancer]]
 
*[[Breast cancer]]
 
*[[Breast cancer]]
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**[[Breast cancer, HER2-positive]]
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**[[Breast cancer, triple negative]]
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*[[Carcinoma of unknown primary]]
 
*[[Cervical cancer]]
 
*[[Cervical cancer]]
−
*[[Colon cancer]]
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*[[Cholangiocarcinoma]]
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*[[Colorectal cancer]]
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**[[Colon cancer]]
 +
**[[Rectal cancer]]
 
*[[Esophageal cancer]]
 
*[[Esophageal cancer]]
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**[[Esophageal adenocarcinoma]]
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**[[Esophageal squamous cell carcinoma]]
 +
*[[Gallbladder cancer]]
 
*[[Gastric cancer]]
 
*[[Gastric cancer]]
 
*[[Head and neck cancer]]
 
*[[Head and neck cancer]]
−
*[[Hepatobiliary cancer]]
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*[[Hepatoblastoma]]
−
*[[Neuroendocrine tumors]]
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*[[Neuroendocrine tumor]]
 
*[[Pancreatic cancer]]
 
*[[Pancreatic cancer]]
 +
*[[Pancreatic NET]]
 
*[[Penile cancer]]
 
*[[Penile cancer]]
−
*[[Prostate cancer]]
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*[[Small bowel adenocarcinoma]]
−
*[[Rectal cancer]]
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==Diseases for which it was used==
−
*[[Unknown primary]]
+
*[[Diffuse large B-cell lymphoma_-_historical|Diffuse large B-cell lymphoma]]
 +
*[[Ovarian cancer - historical|Ovarian cancer]]
 +
*[[Prostate cancer - historical|Prostate cancer]]
  
 
==Patient drug information==
 
==Patient drug information==
 +
*[https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/012209s040lbl.pdf Fluorouracil (5-FU) Package Insert]<ref>[https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/012209s040lbl.pdf Fluorouracil (5-FU) Package Insert]</ref>
 
*[http://chemocare.com/bio/fluorouracil.asp Fluorouracil (5-FU) patient drug information (Chemocare)]<ref>[http://chemocare.com/bio/fluorouracil.asp Fluorouracil (5-FU) patient drug information (Chemocare)]</ref>
 
*[http://chemocare.com/bio/fluorouracil.asp Fluorouracil (5-FU) patient drug information (Chemocare)]<ref>[http://chemocare.com/bio/fluorouracil.asp Fluorouracil (5-FU) patient drug information (Chemocare)]</ref>
 
*[http://www.uptodate.com/contents/fluorouracil-patient-drug-information Fluorouracil (5-FU) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/fluorouracil-patient-drug-information Fluorouracil (5-FU) patient drug information (UpToDate)]</ref>
 
*[http://www.uptodate.com/contents/fluorouracil-patient-drug-information Fluorouracil (5-FU) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/fluorouracil-patient-drug-information Fluorouracil (5-FU) patient drug information (UpToDate)]</ref>
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==History of changes in FDA indication==
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*1962-04-25: Initial FDA approval
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*Uncertain date: Approved for the treatment of patients with [[Colorectal cancer|adenocarcinoma of the colon and rectum]]; [[Breast cancer|adenocarcinoma of the breast]]; [[Gastric cancer|gastric adenocarcinoma]]; and [[Pancreatic cancer|pancreatic adenocarcinoma]]. ''(No supporting studies are cited)''
 +
==History of changes in EMA indication==
 +
*1977-12-16: EURD
 +
 +
==History of changes in PMDA indication==
 +
*2013-12-20: New additional indication and a new dosage for the treatment of unresectable [[pancreatic cancer]].
 +
*2018-09-21: New indication and a new dosage for the treatment of [[Small bowel adenocarcinoma|small intestine cancer]].
 +
*2021-11-25: New indication and a new dosage for the treatment of [[esophageal cancer]].
 +
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==Also known as==
 +
*'''Code name:''' Ro-2-9757
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*'''Generic names:''' 5 Fluorouracil, 5 FU, 5-FU, 5-fluoracilo, 5-fluorouracilo, 5-fluorouracyl, FU
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*'''Brand names:'''
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{| class="wikitable" style="text-align:center;"
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!colspan="8" align="center" style="background-color:#0066FF"| '''Synonyms'''
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|-
 +
|Accusite
 +
|Actino Hermal
 +
|Adrucil
 +
|Arumel
 +
|Benton
 +
|Biofur
 +
|Carac
 +
|Carebin
 +
|-
 +
|Carzonal
 +
|Cinco-FU
 +
|Cinkef-U
 +
|Curacil
 +
|Effcil
 +
|Efudex
 +
|Efurix
 +
|Ezadex
 +
|-
 +
|Fauldfluor
 +
|Fivocil
 +
|Fivoflu
 +
|Flacule
 +
|Flonida
 +
|Florac
 +
|Fluhomer
 +
|Fluolex
 +
|-
 +
|Fluoroplex
 +
|Fluor-Uracil
 +
|Fluoro-Uracile ICN
 +
|Fluoro-Uracil ICN
 +
|Fluorouracile
 +
|Fluorouracilo
 +
|Fluorourcil
 +
|Fluoruracilo
 +
|-
 +
|Fluoxan
 +
|Flurablastin
 +
|Flurac
 +
|Fluracedyl
 +
|Fluracil
 +
|Fluril
 +
|Fluroblastin
 +
|Fluroblastine
 +
|-
 +
|Ftoruracil
 +
|Ftouracil
 +
|Haemato-FU
 +
|Ifacil
 +
|Kang Ning
 +
|Kecimeton Tatumi
 +
|Killit
 +
|Lunachol
 +
|-
 +
|Lunapon
 +
|Natira U
 +
|Neofluor
 +
|O Fluor
 +
|Oncofu
 +
|Onkofluor
 +
|Pentafu
 +
|Pharmauracil
 +
|-
 +
|Phthoruracil
 +
|Phtoruracil
 +
|Ribofluor
 +
|Rotianin
 +
|Satelol
 +
|Seco Uracil
 +
|Tecflu
 +
|Timadin
 +
|-
 +
|Triosules
 +
|Uflahex
 +
|Ulosagen
 +
|Ulup
 +
|Uraciflor
 +
|Utoral
 +
|Vaflu
 +
|Vafu
 +
|-
 +
|}
  
 
==References==
 
==References==
 
<references/>
 
<references/>
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 +
[[Category:Drugs]]
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[[Category:Intravenous medications]]
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[[Category:Topical medications]]
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[[Category:Irritant]]
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[[Category:Fluoropyrimidines]]
 +
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[[Category:Anal cancer medications]]
 +
[[Category:Bladder cancer medications]]
 +
[[Category:Breast cancer medications]]
 +
[[Category:Carcinoma of unknown primary medications]]
 +
[[Category:Cervical cancer medications]]
 +
[[Category:Cholangiocarcinoma medications]]
 +
[[Category:Colon cancer medications]]
 +
[[Category:Colorectal cancer medications]]
 +
[[Category:Esophageal adenocarcinoma medications]]
 +
[[Category:Esophageal cancer medications]]
 +
[[Category:Esophageal squamous cell carcinoma medications]]
 +
[[Category:Gallbladder cancer medications]]
 +
[[Category:Gastric cancer medications]]
 +
[[Category:Head and neck cancer medications]]
 +
[[Category:Hepatoblastoma medications]]
 +
[[Category:Hepatocellular carcinoma medications]]
 +
[[Category:Nasopharyngeal carcinoma medications]]
 +
[[Category:Neuroendocrine tumor medications]]
 +
[[Category:Pancreatic cancer medications]]
 +
[[Category:Pancreatic NET medications]]
 +
[[Category:Penile cancer medications]]
 +
[[Category:Rectal cancer medications]]
 +
[[Category:Small bowel adenocarcinoma medications]]
 +
 +
[[Category:Diffuse large B-cell lymphoma medications (historic)]]
 +
[[Category:Ovarian cancer medications (historic)]]
 +
[[Category:Prostate cancer medications (historic)]]
 +
 +
[[Category:FDA approved in 1962]]
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[[Category:EMA approved in 1977]]
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[[Category:WHO Essential Cancer Medicine]]

Revision as of 01:21, 27 June 2024

General information

Class/mechanism: Pyrimidine analog, antimetabolite, inhibitor of thymidylate synthase. Metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis by binding to thymidylate synthase and inhibiting production of thymidylate; FUTP interferes with RNA processing when it is mistakenly incorporated in place of uridine triphosphate (UTP).[1][2].
Route: IV
Extravasation: irritant

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, UpToDate Lexidrug, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Patient safety

DPYD intermediate or poor metabolizers: Results in higher adverse reaction risk (severe, life-threatening, or fatal toxicities). No dosage has proven safe in poor metabolizers, and insufficient data are available to recommend a dosage in intermediate metabolizers. Withhold or discontinue in the presence of early-onset or unusually severe toxicity.[3]

EMA has recommended that patients should be tested for the lack of the enzyme dihydropyrimidine dehydrogenase (DPD) before starting cancer treatment with fluorouracil given by injection or infusion (drip) or with the related medicines, capecitabine and tegafur.

References

  1. Delaunoit T, Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Findlay BP, Thomas SP, Salim M, Schaefer PL, Stella PJ, Green E, Mailliard JA. Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup Trial N9741. Cancer. 2004 Nov 15;101(10):2170-6. link to original article PubMed

Diseases for which it is established (work in progress)

Diseases for which it is used

Diseases for which it was used

Patient drug information

History of changes in FDA indication

History of changes in EMA indication

  • 1977-12-16: EURD

History of changes in PMDA indication

  • 2013-12-20: New additional indication and a new dosage for the treatment of unresectable pancreatic cancer.
  • 2018-09-21: New indication and a new dosage for the treatment of small intestine cancer.
  • 2021-11-25: New indication and a new dosage for the treatment of esophageal cancer.

Also known as

  • Code name: Ro-2-9757
  • Generic names: 5 Fluorouracil, 5 FU, 5-FU, 5-fluoracilo, 5-fluorouracilo, 5-fluorouracyl, FU
  • Brand names:
Synonyms
Accusite Actino Hermal Adrucil Arumel Benton Biofur Carac Carebin
Carzonal Cinco-FU Cinkef-U Curacil Effcil Efudex Efurix Ezadex
Fauldfluor Fivocil Fivoflu Flacule Flonida Florac Fluhomer Fluolex
Fluoroplex Fluor-Uracil Fluoro-Uracile ICN Fluoro-Uracil ICN Fluorouracile Fluorouracilo Fluorourcil Fluoruracilo
Fluoxan Flurablastin Flurac Fluracedyl Fluracil Fluril Fluroblastin Fluroblastine
Ftoruracil Ftouracil Haemato-FU Ifacil Kang Ning Kecimeton Tatumi Killit Lunachol
Lunapon Natira U Neofluor O Fluor Oncofu Onkofluor Pentafu Pharmauracil
Phthoruracil Phtoruracil Ribofluor Rotianin Satelol Seco Uracil Tecflu Timadin
Triosules Uflahex Ulosagen Ulup Uraciflor Utoral Vaflu Vafu

References

  1. ↑ 1.0 1.1 Fluorouracil (5-FU) package insert (locally hosted backup)
  2. ↑ 5-FU pathway
  3. ↑ [1]
  4. ↑ Fluorouracil (5-FU) Package Insert
  5. ↑ Fluorouracil (5-FU) patient drug information (Chemocare)
  6. ↑ Fluorouracil (5-FU) patient drug information (UpToDate)
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