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{{Short description|Chemotherapy medication}}
{{Use dmy dates|date=July 2023}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 443823794
| verifiedrevid = 456480929
| IUPAC_name = 5-fluoro-1''H''-pyrimidine-2,4-dione
| image = Fluorouracil.svg
| image = Fluorouracil2DACS.svg
| width = 120
| width = 80
| alt =
| image2 = Fluorouracil-3D-vdW.png
| image2 = Fluorouracil-from-xtal-3D-bs-17.png
| width2 = 100
| alt2 =


<!--Clinical data-->
<!--Clinical data-->
| pronounce = {{IPAc-en|ˌ|f|l|ʊər|oʊ|ˈ|j|ʊər|ə|s|ɪ|l}}<ref>{{cite web |title=Fluorouracil – Definition and More from the Free Merriam-Webster Dictionary |url=http://www.merriam-webster.com/dictionary/fluorouracil |access-date=19 November 2014 |url-status=live |archive-url=https://web.archive.org/web/20141129194245/http://www.merriam-webster.com/dictionary/fluorouracil |archive-date=29 November 2014 }}</ref>
| tradename = Carac
| tradename = Adrucil, others
| Drugs.com = {{drugs.com|monograph|fluorouracil}}
| Drugs.com = {{drugs.com|monograph|fluorouracil}}
| MedlinePlus = a682708
| MedlinePlus = a682708
| DailyMedID = Fluorouracil
| pregnancy_AU = D
| pregnancy_AU = D
| pregnancy_category = <br>D (intravenous), X (topical) <small>([[United States|US]])</small>
| pregnancy_category =
| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Topical administration|topical]]
| ATC_prefix = L01
| ATC_suffix = BC02
| ATC_supplemental = {{ATC|L01|BC52}}

| legal_AU = S4
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web|url=https://pdf.hres.ca/dpd_pm/00049486.PDF|title=TOLAK : Fluorouracil Cream : 4% (w/w) fluorouracil (as fluorouracil sodium)|website=Pdf.hres.ca|access-date=8 June 2022|archive-date=10 June 2022|archive-url=https://web.archive.org/web/20220610030126/https://pdf.hres.ca/dpd_pm/00049486.PDF|url-status=live}}</ref>
| legal_UK = POM
| legal_US = Rx-only
| legal_US = Rx-only
| routes_of_administration = [[Intravenous therapy|Intravenous]] (infusion or [[wikt:bolus|bolus]]) and topical


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability = 28 to 100%
| bioavailability = 28 to 100%
| protein_bound = 8 to 12%
| protein_bound = 8 to 12%
| metabolism = Intracellular and [[liver|hepatic]] ([[cytochrome P450|CYP]]-mediated)
| metabolism = Intracellular and [[liver]] ([[cytochrome P450|CYP]]-mediated)
| elimination_half-life = 10 to 20 minutes
| elimination_half-life = 16 minutes
| excretion = [[Kidney|Renal]]
| excretion = [[Kidney]]


<!--Identifiers-->
<!--Identifiers-->
| IUPHAR_ligand = 4789
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 51-21-8
| CAS_number = 51-21-8
| ATC_prefix = L01
| ATC_suffix = BC02
| PubChem = 3385
| PubChem = 3385
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
Line 42: Line 57:


<!--Chemical data-->
<!--Chemical data-->
| IUPAC_name = 5-Fluoro-1''H'',3''H''-pyrimidine-2,4-dione
| C=4 | H=3 | F=1 | N=2 | O=2
| C=4 | H=3 | F=1 | N=2 | O=2
| molecular_weight = 130.077 g/mol
| smiles = c1c(c(=O)[nH]c(=O)[nH]1)F
| smiles = O=C1NC(=O)NC=C1F
| InChI = 1/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
| InChIKey = GHASVSINZRGABV-UHFFFAOYAG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
| StdInChI = 1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GHASVSINZRGABV-UHFFFAOYSA-N
| StdInChIKey = GHASVSINZRGABV-UHFFFAOYSA-N
| melting_point = 282 - 283
| melting_point = 282–283
}}
}}
<!-- Definition and medical uses -->
'''Fluorouracil (5-FU or f5U)''' (sold under the brand names '''Adrucil, Carac, Efudix, Efudex''' and '''Fluoroplex''') is a [[medication|drug]] that is a [[pyrimidine analog]] which is used in the treatment of [[cancer]]. It is a [[suicide inhibition|suicide inhibitor]] and works through irreversible inhibition of [[thymidylate synthase]]. It belongs to the family of drugs called [[antimetabolite]]s. It is typically administered with [[leucovorin]].
'''Fluorouracil''' ('''5-FU''', '''5-fluorouracil'''), sold under the brand name '''Adrucil''' among others, is a [[cytotoxic]] [[chemotherapy]] medication used to treat [[cancer]].<ref name=AHFS2016/> By [[intravenous injection]] it is used for treatment of [[colorectal cancer]], [[oesophageal cancer]], [[stomach cancer]], [[pancreatic cancer]], [[breast cancer]], and [[cervical cancer]].<ref name=AHFS2016>{{cite web|title=Fluorouracil|url=https://www.drugs.com/monograph/fluorouracil.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220192631/https://www.drugs.com/monograph/fluorouracil.html|archive-date=20 December 2016}}</ref> As a cream it is used for [[actinic keratosis]], [[basal cell carcinoma]], and skin [[warts]].<ref name=AHFS2016Top>{{cite web|title=Fluorouracil topical|url=https://www.drugs.com/monograph/fluorouracil-topical.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161226054457/https://www.drugs.com/monograph/fluorouracil-topical.html|archive-date=26 December 2016}}</ref><ref>{{cite journal | vauthors = Moore AY | title = Clinical applications for topical 5-fluorouracil in the treatment of dermatological disorders | journal = The Journal of Dermatological Treatment | volume = 20 | issue = 6 | pages = 328–335 | date = 2009 | pmid = 19954388 | doi = 10.3109/09546630902789326 | s2cid = 218896998 }}</ref>


<!-- Side effects and mechanism -->
== Uses ==
Side effects of use by injection are common.<ref name=AHFS2016/> They may include inflammation of the mouth, loss of appetite, [[cytopenia|low blood cell counts]], hair loss, and inflammation of the skin.<ref name=AHFS2016/> When used as a cream, irritation at the site of application usually occurs.<ref name=AHFS2016Top/> Use of either form in [[pregnancy]] may harm the fetus.<ref name=AHFS2016/> Fluorouracil is in the [[antimetabolite]] and [[pyrimidine analog]] families of medications.<ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=590|edition=69}}</ref><ref>{{cite book| vauthors = Airley R |title=Cancer Chemotherapy: Basic Science to the Clinic|date=2009|publisher=John Wiley & Sons|isbn=9780470092569|page=76|url=https://books.google.com/books?id=wjjYyYpfiQ8C&pg=PA76|language=en|url-status=live|archive-url=https://web.archive.org/web/20171105200744/https://books.google.com/books?id=wjjYyYpfiQ8C&pg=PA76|archive-date=5 November 2017}}</ref> How it works is not entirely clear, but it is believed to involve blocking the action of [[thymidylate synthase]] and thus stopping the production of [[DNA]].<ref name=AHFS2016/>
The chemotherapy agent 5-FU (fluorouracil), which has been in use against cancer for about 40 years, acts in several ways, but principally as a [[thymidylate synthase inhibitor]]. Interrupting the action of this enzyme blocks synthesis of the pyrimidine [[thymidine]], which is a nucleotide required for [[DNA replication]]. [[Thymidylate synthase]] methylates deoxyuridine monophosphate (dUMP) into [[thymidine monophosphate]] (dTMP). Administration of 5-FU causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via [[Thymineless Death|thymineless death]].<ref>{{cite journal |author=Longley DB, Harkin DP, Johnston PG |title=5-fluorouracil: mechanisms of action and clinical strategies |journal=Nat. Rev. Cancer |volume=3 |issue=5 |pages=330–8 |year=2003 |month=May |pmid=12724731 |doi=10.1038/nrc1074 |url=http://www.nature.com/nrc/journal/v3/n5/full/nrc1074.html}}</ref>


<!-- History, society and culture -->
Like many anti-cancer drugs, 5-FU's effects are felt system wide but fall most heavily upon rapidly dividing cells that make heavy use of their nucleotide synthesis machinery, such as cancer cells (other parts of the body with rapidly dividing cells include the cells lining the digestive tract).
Fluorouracil was patented in 1956 and came into medical use in 1962.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=511|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA511|language=en|url-status=live|archive-url=https://web.archive.org/web/20170911002644/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA511|archive-date=11 September 2017}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> In 2021, it was the 281st most commonly prescribed medication in the United States, with more than 800,000 prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Fluorouracil - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Fluorouracil | access-date = 14 January 2024}}</ref>


==Medical uses==
Some of its principal uses are in [[colorectal cancer]], and [[pancreatic cancer]], in which it has been the established form of [[chemotherapy]] for decades ([[platinum]]-containing drugs approved for human use in the US since 1978 are also very well established). It is also sometimes used in the treatment of inflammatory breast cancer, an especially aggressive form of breast cancer.
{{Multiple image
| perrow = 1
| total_width = 200
| direction = vertical
| image1 = Efudix immediately post-treatment.jpg
| width1 = 190px
| alt1 = Male forearm showing oval scabbed skin patch with scales and reddening
| caption1 = Effect of topical skin treatment with 5-fluorouracil cream after a standard 30-day treatment, before commencement of the healing phase (months two and three)
| image2 = Efudix effect three plus years post-treatment.jpg
| width2 = 190px
| alt2 = Male forearm showing healed skin with a creamy, shiny patch having pigmentation loss
| caption2 = Healed skin three+ years after treatment, showing some pigmentation loss
}}
Fluorouracil has been given systemically for [[anal cancer|anal]], [[breast cancer|breast]], [[colorectal cancer|colorectal]], [[oesophageal cancer|oesophageal]], [[stomach cancer|stomach]], [[pancreatic cancer|pancreatic]] and [[skin cancer]]s (especially [[head and neck cancer]]s).<ref name="AMH">{{cite book | veditors = Rossi S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref> It has also been given topically (on the skin) for [[actinic keratoses]], skin cancers and [[Bowen's disease]]<ref name = AMH/> (a type of [[cutaneous squamous-cell carcinoma]]), and as eye drops for treatment of [[ocular surface squamous neoplasia]].<ref>{{cite journal | vauthors = Joag MG, Sise A, Murillo JC, Sayed-Ahmed IO, Wong JR, Mercado C, Galor A, Karp CL | display-authors = 6 | title = Topical 5-Fluorouracil 1% as Primary Treatment for Ocular Surface Squamous Neoplasia | journal = Ophthalmology | volume = 123 | issue = 7 | pages = 1442–1448 | date = July 2016 | pmid = 27030104 | pmc = 4921289 | doi = 10.1016/j.ophtha.2016.02.034 }}</ref> Other uses include ocular injections into a previously created [[trabeculectomy]] [[Bleb (medicine)|bleb]] to inhibit healing and cause scarring of tissue, thus allowing adequate [[aqueous humor]] flow to reduce intraocular pressure.


==Contraindications==
5-FU is also used in ophthalmic surgery, specifically to augment [[trabeculectomy]] (an operation performed to lower the intraocular pressure in patients with [[glaucoma]]) in patients deemed to be at high risk for failure. 5-FU acts as an anti-scarring agent in this regard, since excessive scarring at the trabeculectomy site is the main cause for failure of the surgery.
Fluorouracil is contraindicated in patients who are severely debilitated and in patients with [[bone marrow suppression]] due to either radiotherapy or chemotherapy.<ref name = EMC/> It is likewise contraindicated in pregnant or breastfeeding women.<ref name = EMC/> Non-topical use, i.e. administration by injection, should be avoided in patients who do not have malignant illnesses.<ref name = EMC/>


==Adverse effects==
Fluorouracil can be used topically (as a cream) for treating [[actinic keratosis|actinic (solar) keratoses]] and some types of [[basal cell carcinoma]]s of the skin. It is often referred to by its trade names ''Efudex'', ''Carac'' or ''Fluoroplex''.
Adverse effects by frequency include:<ref name = AMH/><ref name=EMC>{{cite web|title=Fluorouracil 50 mg/ml Injection – Summary of Product Characteristics|work=electronic Medicines Compendium|publisher=Hospira UK Ltd|date=24 August 2011|access-date=24 January 2014|url=http://www.medicines.org.uk/emc/medicine/636/SPC/Fluorouracil++50+mg+ml++Injection/|url-status=live|archive-url=https://web.archive.org/web/20140201204538/http://www.medicines.org.uk/emc/medicine/636/SPC/Fluorouracil++50+mg+ml++Injection/|archive-date=1 February 2014}}</ref><ref name=TGA>{{cite web|title=DBL Fluorouracil Injection BP|work=TGA eBusiness Services|publisher=Hospira Australia Pty Ltd|date=21 June 2012|access-date=24 January 2014|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02952-3|format=PDF|url-status=live|archive-url=https://web.archive.org/web/20170128034658/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02952-3|archive-date=28 January 2017}}</ref><ref name=DM>{{cite web|title=ADRUCIL (fluorouracil) injection [Teva Parenteral Medicines, Inc.]|work=DailyMed|publisher=Teva Parenteral Medicines, Inc.|date=August 2012|access-date=24 January 2014|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b90e0da7-f702-4f09-9488-74f2bb20e9ac|url-status=live|archive-url=https://web.archive.org/web/20140201231133/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b90e0da7-f702-4f09-9488-74f2bb20e9ac|archive-date=1 February 2014}}</ref><ref name=MSRIV>{{cite web|title=Adrucil (fluorouracil) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=24 January 2014|url=http://reference.medscape.com/drug/adrucil-fluorouracil-342092#showall|url-status=live|archive-url=https://web.archive.org/web/20140202174903/http://reference.medscape.com/drug/adrucil-fluorouracil-342092#showall|archive-date=2 February 2014}}</ref>


===During systemic use===
Due to Fluorouracil's toxicity and the fact that it can be manufactured using the same reaction as uracil, its precursor, 5-Fluoroorotic Acid, is commonly used in laboratories to screen against organisms capable of synthesizing uracil.
Common (> 1% frequency):{{div col|colwidth=18em}}
* Nausea
* Vomiting
* Diarrhea (see below for details)
* [[Mucositis]]
* Headache
* [[Hand-foot syndrome]]
* Myelosuppression (see below for details)
* Alopecia (hair loss)
* Photosensitivity
* Maculopapular eruption
* Itch
* Cardiotoxicity (see below for details)
* Persistent [[hiccups]]<ref>[http://medsfacts.com/study-5FU%28FLUOROURACIL%29-causing-HICCUPS.php MedsFacts meta-analysis covering adverse side effect reports of 5fu(fluorouracil) patients who developed hiccups] {{webarchive|url=https://web.archive.org/web/20140905143353/http://medsfacts.com/study-5FU%28FLUOROURACIL%29-causing-HICCUPS.php |date=5 September 2014 }} at MedsFact, 2013</ref>
* Mood disorders (irritability, anxiety, depression)
{{div col end}}


Uncommon (0.1–1% frequency):
It is a key component in [[Tegafur-uracil]].
{{div col|colwidth=18em}}
* [[Oesophagitis]]
* GI ulceration and bleeding
* [[Proctitis]]
* Nail disorders
* Vein pigmentation
* Confusion
* Cerebellar syndrome
* [[Encephalopathy]]
* Visual changes
* [[Photophobia]]
* Lacrimation (the expulsion of tears without any emotional or physiologic reason)
{{div col end}}


Rare (< 0.1% frequency):
== Synthesis ==
* [[Anaphylaxis]]
5-FU was designed, synthesized and patented by Charles Heidelberger in 1957.<ref>{{cite journal |title=Awards, Appointments, Announcements |journal=J Natl Cancer Inst |volume=91 |issue=15 |pages=1278–80 |year=1999 |doi=10.1093/jnci/91.15.1278 |url=http://jnci.oxfordjournals.org/content/91/15/1278.full}}</ref><ref>{{cite journal |author=Chu E |title=Ode to 5-Fluorouracil |journal=Clinical Colorectal Cancer |volume=6 |issue=9 |pages=609 |date=September 2007 |doi=10.3816/CCC.2007.n.029 |url=http://cigjournals.metapress.com/content/b464v2u31594jj28/}}</ref><ref>National Academy of Sciences, Biographical Memoirs,80:135</ref>
* Allergic reactions
* Fever without signs of infection
* Mania, reversible dementia<ref>{{cite journal | vauthors = Ha JH, Hwang DY, Yu J, Park DH, Ryu SH | title = Onset of Manic Episode during Chemotherapy with 5-Fluorouracil | journal = Psychiatry Investigation | volume = 8 | issue = 1 | pages = 71–73 | date = March 2011 | pmid = 21519541 | pmc = 3079190 | doi = 10.4306/pi.2011.8.1.71 }}</ref><ref>Park H. J., Choi Y. T., Kim I. H., Hah J. C.; A case of reversible dementia associated with depression in a patient on 5-FU or its analogue drugs. J. Korean Neuropsychiatr. Assoc. 1987;30:199–202.</ref>


Diarrhea is severe and may be dose-limiting and is exacerbated by co-treatment with [[calcium folinate]].<ref name = AMH/> [[Neutropenia]] tends to peak about 9–14 days after beginning treatment.<ref name = AMH/> [[Thrombocytopenia]] tends to peak about 7–17 days after the beginning of treatment and tends to recover about 10 days after its peak.<ref name = AMH/> [[Cardiotoxicity]] is a fairly common side effect, usually manifesting as [[angina]] or symptoms associated with [[Coronary vasospasm|coronary artery spasm]], but about 0.55% of those receiving the drug will develop life-threatening cardiotoxicity.<ref name="MD">{{cite web|title=Fluorouracil: Martindale: The Complete Drug Reference|date=9 January 2017|url=https://www.medicinescomplete.com/mc/martindale/current/1836-x.htm|access-date=14 August 2017| veditors = Brayfield A |publisher=Pharmaceutical Press|website=MedicinesComplete|location=London, UK|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828090019/https://about.medicinescomplete.com/wp-content/plugins/revslider/public/assets/js/extensions/revolution.extension.slideanims.min.js?version=5.4.5|url-status=live}}</ref> Life-threatening cardiotoxicity includes: [[arrhythmias]], [[ventricular tachycardia]] and [[cardiac arrest]], secondary to transmural ischaemia.<ref name="MD"/>
Since [[uracil]] is a normal component of RNA, the rationale behind the development of the drug was that cancer cells, with their increased genetic instability, might be more sensitive to 'decoy' molecules that mimic the natural compound than normal cells. The scientific goal in this case was to synthesize a drug which demonstrated specific uracil antagonism. The drug proved to have anti-tumor capabilities.


===During topical use===
When elemental fluorine is reacted with [[uracil]], 5-fluorouracil is produced. 5-Fluorouracil masquerades as uracil during the nucleic acid replication process. Because 5-Fluorouracil is similar in shape to, but does not perform the same chemistry as uracil the drug inhibits RNA replication enzymes, thereby eliminating RNA synthesis and stopping the growth of cancerous cells.
Common (> 1% frequency):<ref name = AMH/><ref name=MSRT>{{cite web|title=Efudex, Carac (fluorouracil topical) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=24 January 2014|url=http://reference.medscape.com/drug/efudex-carac-fluorouracil-topical-343545#showall|url-status=live|archive-url=https://web.archive.org/web/20140202174906/http://reference.medscape.com/drug/efudex-carac-fluorouracil-topical-343545#showall|archive-date=2 February 2014}}</ref>
{{div col|colwidth=18em}}
* Local pain
* Itchiness
* Burning
* Stinging
* Crusting
* Weeping
* Dermatitis
* Photosensitivity
{{div col end}}


Uncommon (0.1–1% frequency):
== Mode of action ==
* Hyper- or hypopigmentation
As a [[pyrimidine]] analogue, it is transformed inside the cell into different cytotoxic metabolites which are then incorporated into [[DNA]] and [[RNA]], finally inducing [[cell cycle]] arrest and [[apoptosis]] by inhibiting the cell's ability to synthesize DNA. It is an [[S phase|S-phase]] specific drug and only active during certain cell cycles. In addition to being incorporated in DNA and RNA, the drug has been shown to inhibit the activity of the [[exosome complex]], an [[exoribonuclease]] complex of which the activity is essential for cell survival.
* Scarring


===Neurological damage===
[[Capecitabine]] is a [[prodrug]] that is converted into 5-FU in the tissues. It can be administered orally.
The United States package insert warns that acute cerebellar syndrome has been observed following injection of fluorouracil and may persist after cessation of treatment. Symptoms include [[ataxia]], [[nystagmus]], and [[dysmetria]].<ref>{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e0794add-67a7-4308-93e9-f889472716cc|title=Adrucil (Fluorouracil) Injection [TEVA Parenteral Medicines, Inc.]|url-status=live|archive-url=https://web.archive.org/web/20140814024152/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e0794add-67a7-4308-93e9-f889472716cc|archive-date=14 August 2014}}</ref>


==Potential overdose==
== Adverse effects ==
There is very little difference between the minimum effective dose and maximum tolerated dose of 5-FU, and the drug exhibits marked individual pharmacokinetic variability.<ref name="dose monitoring">{{cite journal | vauthors = Gamelin E, Boisdron-Celle M | title = Dose monitoring of 5-fluorouracil in patients with colorectal or head and neck cancer--status of the art | journal = Critical Reviews in Oncology/Hematology | volume = 30 | issue = 1 | pages = 71–79 | date = March 1999 | pmid = 10439055 | doi = 10.1016/s1040-8428(98)00036-5 }}</ref><ref name="dosing strategies">{{cite journal | vauthors = Felici A, Verweij J, Sparreboom A | title = Dosing strategies for anticancer drugs: the good, the bad and body-surface area | journal = European Journal of Cancer | volume = 38 | issue = 13 | pages = 1677–1684 | date = September 2002 | pmid = 12175683 | doi = 10.1016/s0959-8049(02)00151-x }}</ref><ref name="role of body">{{cite journal | vauthors = Baker SD, Verweij J, Rowinsky EK, Donehower RC, Schellens JH, Grochow LB, Sparreboom A | title = Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001 | journal = Journal of the National Cancer Institute | volume = 94 | issue = 24 | pages = 1883–1888 | date = December 2002 | pmid = 12488482 | doi = 10.1093/jnci/94.24.1883 | doi-access = free }}</ref> Therefore, an identical dose of 5-FU may result in a therapeutic response with acceptable toxicity in some patients and unacceptable and possibly life-threatening toxicity in others.<ref name="dose monitoring"/> Both overdosing and underdosing are of concern with 5-FU, although several studies have shown that the majority of colorectal cancer patients treated with 5-FU are underdosed based on today's dosing standard, body surface area (BSA).<ref name="dose adjustment">{{cite journal | vauthors = Capitain O, Asevoaia A, Boisdron-Celle M, Poirier AL, Morel A, Gamelin E | title = Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study | journal = Clinical Colorectal Cancer | volume = 11 | issue = 4 | pages = 263–267 | date = December 2012 | pmid = 22683364 | doi = 10.1016/j.clcc.2012.05.004 }}</ref><ref name="body surface area">{{cite journal | vauthors = Saam J, Critchfield GC, Hamilton SA, Roa BB, Wenstrup RJ, Kaldate RR | title = Body surface area-based dosing of 5-fluoruracil results in extensive interindividual variability in 5-fluorouracil exposure in colorectal cancer patients on FOLFOX regimens | journal = Clinical Colorectal Cancer | volume = 10 | issue = 3 | pages = 203–206 | date = September 2011 | pmid = 21855044 | doi = 10.1016/j.clcc.2011.03.015 }}</ref><ref name="multicenter evaluation">{{cite journal | vauthors = Beumer JH, Boisdron-Celle M, Clarke W, Courtney JB, Egorin MJ, Gamelin E, Harney RL, Hammett-Stabler C, Lepp S, Li Y, Lundell GD, McMillin G, Milano G, Salamone SJ | display-authors = 6 | title = Multicenter evaluation of a novel nanoparticle immunoassay for 5-fluorouracil on the Olympus AU400 analyzer | journal = Therapeutic Drug Monitoring | volume = 31 | issue = 6 | pages = 688–694 | date = December 2009 | pmid = 19935361 | doi = 10.1097/FTD.0b013e3181b9b8c0 | s2cid = 220558482 }}</ref><ref>{{cite journal | vauthors = Goldberg RM, Rothenberg ML, Van Cutsem E, Benson AB, Blanke CD, Diasio RB, Grothey A, Lenz HJ, Meropol NJ, Ramanathan RK, Becerra CH, Wickham R, Armstrong D, Viele C | display-authors = 6 | title = The continuum of care: a paradigm for the management of metastatic colorectal cancer | journal = The Oncologist | volume = 12 | issue = 1 | pages = 38–50 | date = January 2007 | pmid = 17227899 | doi = 10.1634/theoncologist.12-1-38 | s2cid = 21638678 | doi-access = free }}</ref> The limitations of BSA-based dosing prevent oncologists from being able to accurately titer the dosage of 5-FU for the majority of individual patients, which results in sub-optimal treatment efficacy or excessive toxicity.<ref name="dose adjustment"/><ref name="body surface area"/>
[[Adverse drug reaction|Side effect]]s include [[myelosuppression]], [[mucositis]], [[dermatitis]], [[diarrhea]] and [[cardiac toxicity]].


Numerous studies have found significant relationships between concentrations of 5-FU in blood plasma and both desirable or undesirable effects on patients.<ref>{{cite journal | vauthors = Ploylearmsaeng SA, Fuhr U, Jetter A | title = How may anticancer chemotherapy with fluorouracil be individualised? | journal = Clinical Pharmacokinetics | volume = 45 | issue = 6 | pages = 567–592 | year = 2006 | pmid = 16719540 | doi = 10.2165/00003088-200645060-00002 | s2cid = 36534309 }}</ref><ref>{{cite journal | vauthors = van Kuilenburg AB, Maring JG | title = Evaluation of 5-fluorouracil pharmacokinetic models and therapeutic drug monitoring in cancer patients | journal = Pharmacogenomics | volume = 14 | issue = 7 | pages = 799–811 | date = May 2013 | pmid = 23651027 | doi = 10.2217/pgs.13.54 }}</ref> Studies have also shown that dosing based on the concentration of 5-FU in plasma can greatly increase desirable outcomes while minimizing negative side effects of 5-FU therapy.<ref name="dose adjustment"/><ref name="individual fluorouracil">{{cite journal | vauthors = Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M | display-authors = 6 | title = Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer | journal = Journal of Clinical Oncology | volume = 26 | issue = 13 | pages = 2099–2105 | date = May 2008 | pmid = 18445839 | doi = 10.1200/jco.2007.13.3934 | s2cid = 9557055 | doi-access = free }}</ref> One such test that has been shown to successfully monitor 5-FU plasma levels and which "may contribute to improved efficacy and safety of commonly used 5-FU-based chemotherapies" is the My5-FU test.<ref name="multicenter evaluation"/><ref>{{cite web|url=http://Mycaretests.com|title=Customizing Chemotherapy for Better Cancer Care|publisher=MyCare Diagnostics|url-status=dead|archive-url=https://web.archive.org/web/20140428135326/http://www.mycaretests.com/|archive-date=28 April 2014}}</ref><ref>{{cite web|url=http://bettercancercare.com|title=A Brief History of BSA Dosing|publisher=MyCare Diagnostics|url-status=live|archive-url=https://web.archive.org/web/20140428195606/http://bettercancercare.com/|archive-date=28 April 2014}}</ref>
5-FU injection and topical even in small doses cause both acute [[central nervous system|CNS]] damage and progressively worsening delayed degeneration of the CNS in mice. This latter effect is caused by 5-FU-induced damage to the [[oligodendrocytes]] that produce the insulating [[myelin]] sheaths.<ref>[http://www.urmc.rochester.edu/biomedical-genetics/faculty/chemotherapy-induced-damage-to-cns.cfm "Chemotherapy-induced Damage to the CNS as a Precursor Cell Disease"] by Dr. Mark D. Noble, University of Rochester</ref>


== Interactions ==
When using a pyrimidine-based drug, users must be aware that some people have a genetic inability to metabolize them. Current theory points to nearly 8% of the population having what is termed [[DPD deficiency]]. There are laboratory tests to determine the relative activity of the DPD enzyme. Many labs offer DPD testing: Laboratory Corporation of America was one of the first to make the test available commercially on a large scale (Test Number 511176). [[MYGN|Myriad Genetic Laboratories]] in [[Salt Lake City, UT]] also offers a test. In addition to full sequence analysis of the DPYD gene, Myriad performs an analysis of the TYMS gene which accounts for moderate gastrointestinal toxicities. Coventry Diagnostics in [[Troy, Michigan|Troy, MI]] and DNAVision ([[Belgium]]) have quantitative analyses. GenPath diagnostics in [[Elmwood Park, NJ]] is also offering this test as a part of their pharmacogenomics effort. Additionally, EntroGen now offers genotyping reagents to clinical laboratories interested in developing an in-house DPYD mutation screen. It is expected that with a potential 500,000 people in North America using the pyrimidine-based 5-FU, this form of testing will increase.


It may increase the INR and prothrombin times in people on [[warfarin]].<ref name = EMC/> Fluorouracil's efficacy is decreased when used alongside [[allopurinol]], which can be used to decrease fluorouracil induced stomatitis through use of allopurinol mouthwash.<ref name="pmid8192112">{{cite journal | vauthors = Porta C, Moroni M, Nastasi G | title = Allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis | journal = American Journal of Clinical Oncology | volume = 17 | issue = 3 | pages = 246–247 | date = June 1994 | pmid = 8192112 | doi = 10.1097/00000421-199406000-00014 | s2cid = 26844431 }}</ref>
The typical starting dose of capecitabine is 2,500&nbsp;mg/m2 per day in Europe and 2,000&nbsp;mg/m2 per day in the US. Probably the main action of 5-FU occurs when a 5-FU metabolite binds to thymidylate synthase. This binding is stable only in the presence of methylenetetrahydrofolate. It is speculated that this may explain why people in the US—a country that mandates adding folic acid to some foods—apparently require a lower dose of capecitabine than people in Europe—countries that do not mandate added folic acid.<ref>{{cite journal |author=Midgley R, Kerr DJ |title=Capecitabine: have we got the dose right? |journal=Nat Clin Pract Oncol |volume=6 |issue=1 |pages=17–24 |year=2009 |month=January |pmid=18936793 |doi=10.1038/ncponc1240 |url=http://www.nature.com/nrclinonc/journal/v6/n1/full/ncponc1240.html}}
</ref><ref>{{cite web |author=Midgley, Rachel |title=Regional Variation in Capecitabine Metabolism and Toxicity |publisher=Medscape.com |url=http://www.medscape.com/viewarticle/583704_3}}
</ref>


==Pharmacology==
The body converts both folic acid and [[leucovorin]] to methylenetetrahydrofolate.
Each of those precursors amplify the effect of 5-FU in one animal study.<ref>
{{cite journal |author=Raghunathan K, Priest DG |title=Modulation of fluorouracil antitumor activity by folic acid in a murine model system |journal=Biochem. Pharmacol. |volume=58 |issue=5 |pages=835–9 |year=1999 |month=September |pmid=10449194 |url=http://linkinghub.elsevier.com/retrieve/pii/S0006-2952(99)00157-4 |doi=10.1016/S0006-2952(99)00157-4}}
</ref> However, another animal study seemed to indicate that, given the same 5-FU treatment, that a special diet containing no folic acid (0 ppm) worked better than the normal diet.<ref>
{{cite journal |author=Tucker JM, Davis C, Kitchens ME, ''et al.'' |title=Response to 5-fluorouracil chemotherapy is modified by dietary folic acid deficiency in Apc(Min/+) mice |journal=Cancer Lett. |volume=187 |issue=1–2 |pages=153–62 |year=2002 |month=December |pmid=12359363 |url=http://linkinghub.elsevier.com/retrieve/pii/S0304383502004020 |doi=10.1016/S0304-3835(02)00402-0}}</ref>


===Pharmacogenetics===
Folic acid may amplify the desired action and the toxicity of 5-FU.
The exact mechanism of interaction is unknown.<ref>[http://www.drugs.com/drug-interactions/folic-acid_d00241_xeloda_d04311.html "Folic-acid and Xeloda Interactions"]</ref>


The [[dihydropyrimidine dehydrogenase]] (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes 5-fluorouracil, [[capecitabine]], and [[tegafur]].<ref name="pmid23988873">{{cite journal | vauthors = Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M | title = Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 6 | pages = 640–645 | date = December 2013 | pmid = 23988873 | pmc = 3831181 | doi = 10.1038/clpt.2013.172 }}</ref> [[Genetic variation]]s within the DPD gene (''DPYD'') can lead to reduced or absent DPD activity, and individuals who are [[heterozygous]] or [[homozygous]] for these variations may have partial or complete [[DPD deficiency]]; an estimated 0.2% of individuals have complete [[DPD deficiency]].<ref name="pmid23988873"/><ref name="pmid21919607">{{cite journal | vauthors = Amstutz U, Froehlich TK, Largiadèr CR | title = Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity | journal = Pharmacogenomics | volume = 12 | issue = 9 | pages = 1321–1336 | date = September 2011 | pmid = 21919607 | doi = 10.2217/pgs.11.72 }}</ref> Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include [[myelosuppression]], [[neurotoxicity]] and [[hand-foot syndrome]].<ref name="pmid23988873"/><ref name="pmid21919607"/>
When 5-FU is given [[intravenously]], it is typically mixed with [[leucovorin]] in order to increase 5-FU activity. Folic acid may work as well as leucovorin, but the one human study performed (with a high dose of folic acid, from 40&nbsp;mg/m<sup>2</sup> to 140&nbsp;mg/m<sup>2</sup>) had disappointing results and concluded that further studies were needed.<ref>[http://books.google.com/books?id=mst5gVH6WUcC&pg=PA207&lpg=PA207&dq=Fluorouracil++folic+acid&source=bl&ots=UyQaJKJbKg&sig=yRWu9ms-4MWv4EQokYmjwi_HPeM&hl=en&ei=CmPTScejMZrslQfhzpz7Cw&sa=X&oi=book_result&resnum=10&ct=result "Handbook of drug-nutrient interactions"] by Joseph I. Boullata, Vincent T. Armenti, 2007, p.207, 208</ref> There is some confusion about whether the amount of folic acid in a normal diet and multivitamins is enough to interact badly with 5-FU.<ref>[http://www.medkb.com/Uwe/Forum.aspx/cancer-forum/16/Xeloda-and-Folic-acid "Xeloda and Folic acid"]</ref>


===Mechanism of action===
One study showed that 79 percent of the patients who switched from 5-FU (with leucovorin) to Xeloda ([[capecitabine]]) had serious side effects. None of the patients who switched from Xeloda to 5-FU (with leucovorin) had serious side effects. The researchers were unsure of why.<ref>
5-FU acts in several ways, but principally as a [[thymidylate synthase inhibitor|thymidylate synthase (TS) inhibitor]]. Interrupting the action of this enzyme blocks synthesis of the pyrimidine [[Thymidine monophosphate|thymidylate (dTMP)]], which is a [[nucleotide]] required for [[DNA replication]]. [[Thymidylate synthase]] methylates deoxyuridine monophosphate (dUMP) to form [[thymidine monophosphate]] (dTMP). Administration of 5-FU causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via [[thymineless death]].<ref>{{cite journal | vauthors = Longley DB, Harkin DP, Johnston PG | title = 5-fluorouracil: mechanisms of action and clinical strategies | journal = Nature Reviews. Cancer | volume = 3 | issue = 5 | pages = 330–338 | date = May 2003 | pmid = 12724731 | doi = 10.1038/nrc1074 | s2cid = 4357553 }}</ref> Calcium folinate provides an exogenous source of reduced folinates and hence stabilises the 5-FU-TS complex, hence enhancing 5-FU's cytotoxicity.<ref>{{cite journal | vauthors = Álvarez P, Marchal JA, Boulaiz H, Carrillo E, Vélez C, Rodríguez-Serrano F, Melguizo C, Prados J, Madeddu R, Aranega A | display-authors = 6 | title = 5-Fluorouracil derivatives: a patent review | journal = Expert Opinion on Therapeutic Patents | volume = 22 | issue = 2 | pages = 107–123 | date = February 2012 | pmid = 22329541 | doi = 10.1517/13543776.2012.661413 | s2cid = 2793746 }}</ref>
[http://fightcolorectalcancer.org/research_news/2008/07/switching_from_5fu_to_xeloda_can_cause_significant_side_effects "Switching from 5FU to Xeloda Can Cause Significant Side Effects"]</ref>


==History==
Trissel and colleagues have shown that 5-FU and leucovorin are physically incompatible when mixed in portable-pump reservoirs. <ref>{{cite journal |author=Trissel LA, Martinez JF, Xu QA |title=Incompatibility of fluorouracil with leucovorin calcium or levoleucovorin calcium |journal=Am J Health Syst Pharm |volume=52 |issue=7 |pages=710–5 |year=1995 |month=April |pmid=7627739 }}</ref> Similarly, infusion of 5-FU and leucovorin via permanent indwelling catheters is complicated by catheter blockage due to calcium carbonate formation (Ardalan and Flores, 1995). <ref>{{cite journal |author=Ardalan B, Flores MR |title=A new complication of chemotherapy administered via permanent indwelling central venous catheter |journal=Cancer |volume=75 |issue=8 |pages=2165–8 |year=1995 |month=April |pmid=7697607 |doi=10.1002/1097-0142(19950415)75:8<2165::AID-CNCR2820750821>3.0.CO;2-W }}</ref>
In 1954, Abraham Cantarow and Karl Paschkis found liver tumors absorbed radioactive [[uracil]] more readily than did normal liver cells. [[Charles Heidelberger]], who had earlier found that fluorine in [[fluoroacetic acid]] inhibited a vital enzyme, asked Robert Duschinsky and Robert Schnitzer at [[Hoffmann-La Roche]] to synthesize fluorouracil.<ref>{{cite book | vauthors = Sneader W | title = Drug discovery: a history. | publisher = John Wiley & Sons | date = June 2005 | page = 255 }}</ref> Some credit Heidelberger and Duschinsky with the discovery that 5-fluorouracil markedly inhibited tumors in mice.<ref>{{cite journal | vauthors = Cohen S |title=50 years ago in cell biology: A virologist recalls his work on cell growth inhibition |journal=The Scientist |date=30 January 2008 |url=http://www.the-scientist.com/news/display/54259/ |url-status=live |archive-url=https://web.archive.org/web/20100919181108/http://www.the-scientist.com/news/display/54259/ |archive-date=19 September 2010 }}</ref> The original 1957 report<ref>{{cite journal | vauthors = Chu E |title=Ode to 5-Fluorouracil |journal=Clinical Colorectal Cancer |volume=6 |issue=9 |pages=609 |date=September 2007 |doi=10.3816/CCC.2007.n.029 |url=http://cigjournals.metapress.com/content/b464v2u31594jj28/ |url-status=dead |archive-url=https://archive.today/20120714082218/http://cigjournals.metapress.com/content/b464v2u31594jj28/ |archive-date=14 July 2012 }}</ref><ref>{{cite journal | vauthors = Heidelberger C, Chaudhuri NK, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer RJ, Pleven E, Scheiner J | display-authors = 6 | title = Fluorinated pyrimidines, a new class of tumour-inhibitory compounds | journal = Nature | volume = 179 | issue = 4561 | pages = 663–666 | date = March 1957 | pmid = 13418758 | doi = 10.1038/179663a0 | s2cid = 4296069 | bibcode = 1957Natur.179..663H }}</ref>
In 1958, Anthony R. Curreri, [[Fred J. Ansfield]], Forde A. McIver, Harry A. Waisman, and Charles Heidelberger reported the first clinical findings of 5-FU's activity in cancer in humans.<ref>{{cite journal | vauthors = Jordan VC | title = A Retrospective: On Clinical Studies with 5-Fluorouracil | journal = Cancer Research | volume = 76 | issue = 4 | pages = 767–768 | date = February 2016 | pmid = 26880809 | doi = 10.1158/0008-5472.CAN-16-0150 | url = https://cancerres.aacrjournals.org/content/76/4/767 | access-date = 17 August 2019 | publisher = American Association for Cancer Research | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20210828090010/https://cancerres.aacrjournals.org/content/76/4/767 | archive-date = 28 August 2021 }}</ref>


== History ==
==Natural analogues==
In 2003, scientists isolated 5-fluorouracil derivatives, closely related compounds, from the marine sponge, ''[[Phakellia]] fusca'', collected around [[Yongxing Island]] of the [[Xisha Islands]] in the [[South China Sea]]. This is significant because fluorine-containing [[natural products]] are extremely rare.<ref>{{cite journal | vauthors = Xu XH, Yao GM, Li YM, Lu JH, Lin CJ, Wang X, Kong CH | title = 5-Fluorouracil derivatives from the sponge Phakellia fusca | journal = Journal of Natural Products | volume = 66 | issue = 2 | pages = 285–288 | date = February 2003 | pmid = 12608868 | doi = 10.1021/np020034f }}</ref>
In 1954 [[Abraham Cantarow]] and [[Karl Paschkis]] found liver tumors absorbed radioactive [[uracil]] more readily than normal liver cells. [[Charles Heidelberger]], who had earlier found that fluorine in [[fluoroacetic acid]] inhibited a vital enzyme, asked [[Robert Duschinsky]] and [[Robert Schnitzer]] at [[Hoffman-La Roche]] to synthesize fluorouracil.<ref>Sneader W. (2005). ''Drug Discovery'', p. 255.</ref> Some credit Heidelberger and Duschinsky with the discovery that 5-fluorouracil markedly inhibited tumors in mice.<ref>{{cite journal |author=Cohen, Seymour |title=50 years ago in cell biology: A virologist recalls his work on cell growth inhibition |journal=The Scientist |date=30 January 2008 |url=http://www.the-scientist.com/news/display/54259/}}</ref> The original 1957 report in Nature has Heidelberger as lead author, along with N.K.Chaudhuri, Peter Danneberg, Dorothy Mooren, Louis Griesbach, Robert Duschinsky, R.J. Schnitzer, E. Pleven, and J. Scheiner.<ref>{{cite journal |author=Heidelberger C, Chaudhuri NK, Danneberg P, ''et al.'' |title=Fluorinated pyrimidines, a new class of tumour-inhibitory compounds |journal=Nature |volume=179 |issue=4561 |pages=663–6 |year=1957 |month=March |pmid=13418758 |doi=10.1038/179663a0 }}</ref>


== Interactive pathway map ==
==Interactive pathway map==
{{FluoropyrimidineActivity WP1601}}
{{FluoropyrimidineActivity WP1601}}


==References==
==Names==
The name "fluorouracil" is the [[international nonproprietary name|INN]], [[United States Adopted Name|USAN]], [[United States Pharmacopeia|USP]] name, and [[British Approved Name|BAN]]. The form "5-fluorouracil" is often used; it shows that there is a fluorine atom on the 5th carbon of a [[uracil]] ring.

== References ==
{{reflist}}
{{reflist}}

== Further reading ==
* {{cite book | title=Medical Genetics Summaries | chapter=Fluorouracil Therapy and DPYD Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK395610/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2016 | pmid=28520376 | id=Bookshelf ID: NBK395610 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}
* {{cite journal | vauthors = Latchman J, Guastella A, Tofthagen C | title = 5-Fluorouracil toxicity and dihydropyrimidine dehydrogenase enzyme: implications for practice | journal = Clinical Journal of Oncology Nursing | volume = 18 | issue = 5 | pages = 581–585 | date = October 2014 | pmid = 25253112 | pmc = 5469441 | doi = 10.1188/14.CJON.581-585 }}


== External links ==
== External links ==
* {{cite web | title=Fluorouracil Topical | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a605010.html }}
* [http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Individualdrugs/Fluorouracil Cancerbackup.org.uk &ndash; Fluorouracil's use in cancer]


{{Chemotherapeutic agents}}
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[[Category:Fluoropyrimidines]]
[[Category:Nucleobases]]
[[Category:Organofluorides]]
[[Category:Organofluorides]]
[[Category:Antineoplastic antimetabolites]]
[[Category:Pyrimidine antagonists]]
[[Category:Pyrimidinediones]]
[[Category:Pyrimidinediones]]
[[Category:Thymidylate synthase inhibitors]]
[[Category:Thymidylate synthase inhibitors]]
[[Category:Uracil derivatives]]

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