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

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
m (Text replacement - "[http://online.lexi.com/ Lexicomp]" to "[https://online.lexi.com/lco/action/login UpToDate Lexidrug]")
(16 intermediate revisions by 2 users not shown)
Line 1: Line 1:
 
==General information==
 
==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).<ref name="insert">[[:File: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>.
+
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]]
  
−
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==
 
==Patient safety==
Line 11: Line 11:
 
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.
 
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.
  
−
==Diseases for which it is established==
+
===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]]
 
*[[Hepatocellular carcinoma]]
 +
*[[Nasopharyngeal carcinoma]]
  
 
==Diseases for which it is used==
 
==Diseases for which it is used==
Line 23: Line 27:
 
*[[Cervical cancer]]
 
*[[Cervical cancer]]
 
*[[Cholangiocarcinoma]]
 
*[[Cholangiocarcinoma]]
−
*[[Colon cancer]]
+
*[[Colorectal cancer]]
 +
**[[Colon cancer]]
 +
**[[Rectal cancer]]
 
*[[Esophageal cancer]]
 
*[[Esophageal cancer]]
 
**[[Esophageal adenocarcinoma]]
 
**[[Esophageal adenocarcinoma]]
Line 31: Line 37:
 
*[[Head and neck cancer]]
 
*[[Head and neck cancer]]
 
*[[Hepatoblastoma]]
 
*[[Hepatoblastoma]]
−
*[[Nasopharyngeal carcinoma]]
 
 
*[[Neuroendocrine tumor]]
 
*[[Neuroendocrine tumor]]
 
*[[Pancreatic cancer]]
 
*[[Pancreatic cancer]]
 
*[[Pancreatic NET]]
 
*[[Pancreatic NET]]
 
*[[Penile cancer]]
 
*[[Penile cancer]]
−
*[[Rectal cancer]]
+
*[[Small bowel adenocarcinoma]]
−
 
 
 
==Diseases for which it was used==
 
==Diseases for which it was used==
 
*[[Diffuse large B-cell lymphoma_-_historical|Diffuse large B-cell lymphoma]]
 
*[[Diffuse large B-cell lymphoma_-_historical|Diffuse large B-cell lymphoma]]
Line 49: Line 53:
  
 
==History of changes in FDA indication==
 
==History of changes in FDA indication==
−
* 4/25/1962: Initial FDA approval
+
*1962-04-25: Initial FDA approval
 +
*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]].
  
 
==Also known as==
 
==Also known as==
 
*'''Code name:''' Ro-2-9757
 
*'''Code name:''' Ro-2-9757
−
*'''Generic names:''' 5 Fluorouracil, 5 FU, 5-fluoracilo, 5-fluorouracilo, 5-fluorouracyl, FU
+
*'''Generic names:''' 5 Fluorouracil, 5 FU, 5-FU, 5-fluoracilo, 5-fluorouracilo, 5-fluorouracyl, FU
 
*'''Brand names:'''
 
*'''Brand names:'''
 
{| class="wikitable" style="text-align:center;"
 
{| class="wikitable" style="text-align:center;"
Line 158: Line 170:
 
[[Category:Cholangiocarcinoma medications]]
 
[[Category:Cholangiocarcinoma medications]]
 
[[Category:Colon cancer medications]]
 
[[Category:Colon cancer medications]]
 +
[[Category:Colorectal cancer medications]]
 
[[Category:Esophageal adenocarcinoma medications]]
 
[[Category:Esophageal adenocarcinoma medications]]
 
[[Category:Esophageal cancer medications]]
 
[[Category:Esophageal cancer medications]]
Line 172: Line 185:
 
[[Category:Penile cancer medications]]  
 
[[Category:Penile cancer medications]]  
 
[[Category:Rectal cancer medications]]
 
[[Category:Rectal cancer medications]]
 +
[[Category:Small bowel adenocarcinoma medications]]
  
 
[[Category:Diffuse large B-cell lymphoma medications (historic)]]
 
[[Category:Diffuse large B-cell lymphoma medications (historic)]]
Line 178: Line 192:
  
 
[[Category:FDA approved in 1962]]
 
[[Category:FDA approved in 1962]]
 +
[[Category:EMA approved in 1977]]
 
[[Category:WHO Essential Cancer Medicine]]
 
[[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)
Retrieved from "https://hemonc.org/w/index.php?title=Fluorouracil_(5-FU)&oldid=86982"