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			{{short description|Chemotherapy medication}}
	{{Drugbox		{{Drugbox
			|Watchedfields = changed
	| verifiedrevid = 443748102
			|verifiedrevid = 458447760
	| IUPAC_name = 4'-demethyl-epipodophyllotoxin 9-, 4' -(dihydrogen phosphate)
	| image = Etoposide.svg		|image = Etoposide.svg
			|image2 = Etoposide ball-and-stick.png
	<!--Clinical data-->		<!--Clinical data-->
			|pronounce = {{IPAc-en|ˌ|ɛ|t|oʊ-|ˈ|p|oʊ|s|aɪ|d}}
	| tradename = Vepesid
			|tradename = Etopophos, Toposar, Vepesid, others
	| Drugs.com = {{drugs.com|monograph|etoposide}}
			|Drugs.com = {{drugs.com|monograph|etoposide}}
	| MedlinePlus = a684055
			|MedlinePlus = a684055
	| pregnancy_AU = D
	| pregnancy_US = D		|pregnancy_AU = D
	| legal_UK = POM		|pregnancy_US = D
			|legal_UK = POM
	| legal_US = Rx-only
			|legal_US = Rx-only
	| routes_of_administration = Oral, ]
			|routes_of_administration = ], ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = Highly variable, 25 to 75%		|bioavailability = Highly variable, 25 to 75%
	| protein_bound = 97%		|protein_bound = 97%
	| metabolism = ] (] involved)		|metabolism = ] (] involved)
	| elimination_half-life = Oral: 6 h., IV: 6-12 h., IV in children: 3 h.		|elimination_half-life = Oral: 6 h., IV: 6-12 h., IV in children: 3 h.
	| excretion = ] and fecal		|excretion = ] and fecal
	<!--Identifiers-->		<!--Identifiers-->
			|index2_label = as salt
	| CASNo_Ref = {{cascite|correct|CAS}}
			|IUPHAR_ligand = 6815
	| CAS_number_Ref = {{cascite|correct|??}}
			|CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 33419-42-0
			|CAS_number = 33419-42-0
	| ATC_prefix = L01
	| ATC_suffix = CB01		|ATC_prefix = L01
			|ATC_suffix = CB01
	| ATC_supplemental =
			|ATC_supplemental =
	| PubChem = 36462
			|PubChem = 36462
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			|DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00773
			|DrugBank = DB00773
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 33510
	| UNII_Ref = {{fdacite|correct|FDA}}		|ChemSpiderID = 33510
			|UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 6PLQ3CP4P3		|UNII = 6PLQ3CP4P3
	| KEGG_Ref = {{keggcite|correct|kegg}}		|KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00125		|KEGG = D00125
	| ChEBI_Ref = {{ebicite|correct|EBI}}		|KEGG2_Ref = {{keggcite|correct|kegg}}
	| ChEBI = 4911		|KEGG2 = D04107
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		|ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 44657		|ChEBI = 4911
			|ChEMBL_Ref = {{ebicite|correct|EBI}}
			|ChEMBL = 44657
			|synonyms = VP-16; VP-16-213
	<!--Chemical data-->		<!--Chemical data-->
			|IUPAC_name = 4'-Demethyl-epipodophyllotoxin 9-, 4' -(dihydrogen phosphate)
	| C=29 | H=32 | O=13
			|C=29|H=32|O=13
	| molecular_weight = 588.557 g/mol
			|melting_point = 243.5
	| smiles = C1OC2(O1)(((O2)O3c4cc5c(cc4(63COC6=O)c7cc(c(c(c7)OC)O)OC)OCO5)O)O
			|smiles = C1OC2(O1)(((O2)O3c4cc5c(cc4(63COC6=O)c7cc(c(c(c7)OC)O)OC)OCO5)O)O
	| InChI = 1/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
			|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| InChIKey = VJJPUSNTGOMMGY-MRVIYFEKBZ
			|StdInChI = 1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
			|StdInChIKey = VJJPUSNTGOMMGY-MRVIYFEKSA-N
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = VJJPUSNTGOMMGY-MRVIYFEKSA-N
	}}		}}
			<!--Definition and medical uses-->
	'''Etoposide phosphate''' (brand names: '''Eposin''', '''Etopophos''', '''Vepesid''', '''VP-16''') is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting. Unlike enzyme inhibitors, it exploits the normal mechanism of action of the ] ], which aids in DNA unwinding, and by doing so causes DNA strands to break. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. It is used as a form of ] for cancers such as ], ], ], ], non-lymphocytic ], and ]. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a ] or ] transplant.
			'''Etoposide''', sold under the brand name '''Vepesid''' among others, is a ] used for the treatments of a number of types of ] including ], ], ], ], ], and ].<ref name=AHFS2016/> It is also used for ].<ref>{{cite journal|vauthors = Yildiz H, Van Den Neste E, Defour JP, Danse E, Yombi JC|title = Adult haemophagocytic lymphohistiocytosis: a Review|journal = QJM|volume = 115|issue = 4|pages = 205–213|date = January 2020|pmid = 31943120|doi = 10.1093/qjmed/hcaa011|doi-access = free}}</ref> It is used by mouth or ].<ref name=AHFS2016/>
			<!--Side effects and mechanism-->
	Its chemical make-up derives from ], a toxin found in the ].
			Side effects are very common.<ref name=AHFS2016/> They can include ], vomiting, loss of appetite, diarrhea, hair loss, and fever.<ref name=AHFS2016/> Other severe side effects include ] and ].<ref name=AHFS2016/><ref name=WHO2008>{{cite book|title = WHO Model Formulary 2008|year = 2009|isbn = 9789241547659|vauthors = ((World Health Organization))|veditors = Stuart MC, Kouimtzi M, Hill SR|hdl = 10665/44053|author-link = World Health Organization|publisher = World Health Organization|hdl-access=free|page=227}}</ref> Use during ] will likely harm the fetus.<ref name=AHFS2016/> Etoposide is in the ] family of medication.<ref name=AHFS2016/> It is believed to work by damaging DNA.<ref name=AHFS2016/>
			<!--History, society, and culture-->
	The name VP-16 likely comes from a compounding of the last name of the chemists who performed early work on the drug (von Wartburg and von Kuhn) and podophyllotoxin<ref>{{cite journal |author=Kuhn M, Von Wartbung A |title=''Podophyllum''- Lignane: Struktur und Absolutkonfiguration von Podorhizol-β-D-glucosid ( = Lignan F). 19. Mitt. über mitosehemmende Naturstoffe <nowiki></nowiki> |journal=Helvetica Chimica Acta |volume=50 |issue=6 |pages=1546–65 |year=1967 |doi=10.1002/hlca.19670500614 |url=http://www3.interscience.wiley.com/journal/109731280/abstract}}</ref>. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist].
			Etoposide was approved for medical use in the United States in 1983.<ref name=AHFS2016>{{cite web|title=Etoposide|url=https://www.drugs.com/monograph/etoposide.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20160331070620/http://www.drugs.com/monograph/etoposide.html|archive-date=31 March 2016}}</ref> It is on the ].<ref name="WHO21st">{{cite book|vauthors = ((World Health Organization))|title = World Health Organization model list of essential medicines: 21st list 2019|year = 2019|hdl = 10665/325771|author-link = World Health Organization|publisher = World Health Organization|location = Geneva|id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO|hdl-access=free}}</ref>
	==Mechanism of Action==		==Medical uses==
			Etoposide is used as a form of ] for cancers such as ], ], ], ], ], nonlymphocytic ], and ]. It is often given in combination with other drugs (such as ] in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to a ] or ] transplant.<ref name="wow"/>
	Etoposide forms a ternary complex with DNA and the ] enzyme, preventing re-ligation of the DNA strands. This causes errors in DNA synthesis and promotes apoptosis of the cancer cell. <ref>{{cite journal |author=Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA |title=Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives |journal=Toxicon |volume=44 |issue=4 |pages=441–59 |year=2004 |doi=10.1016/j.toxicon.2004.05.008 |pmid=15302526}}</ref>
	==Administration==		===Administration===
	It is given intravenously or orally in capsule form. If the drug is given by IV it must be done slowly over a 30 to 60 minute period because it can lower ] as it is being administered. Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.		It is given ] (IV) or orally in capsule or tablet form. If the drug is given IV, it must be done slowly over a 30- to 60-minute period because it can lower ] as it is being administered.<ref name="AHFS2016" /> Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.{{cn|date=December 2023}}
			==Side effects==
	In general, patients are advised to call their doctor in case of ], symptoms of ] or painful injection sites, as these may progress severely without adequate medical attention.
	Patients are advised to drink large amounts of fluids after treatment to prevent damage to the ] and ]s, typically 1.5 to 3.5 litres of ] on the day of treatment and for several days after.
	==Side-effects==
	Common are:		Common are:
			*infusion site reactions
	* ]
			*]
	* ]
			*]
	* pain and or burning at the IV site
			*pain and or burning at the IV site
	* ] or ]
			*] or ]
	* ]
			*]
	* ] suppression, leading to:
	** decreased ] counts (leading to increased susceptibility to ]s)		*] suppression, leading to:
			**decreased ] counts (leading to increased susceptibility to ]s)
	** low ] counts (])		**low ] counts (])
	** low ] counts (leading to easy bruising and bleeding)		**low ] counts (leading to easy bruising and bleeding)
	Less common are:		Less common are:
	* ] and vomiting		*] and vomiting
	* allergic type reactions		*allergic-type reactions
	* ]		*]
	* ], often occurring shortly after IV administration and not due to ]		*], often occurring shortly after IV administration and not due to ]
	* ]		*]
	* ]		*] (which can be treated with etoposide itself)
			When given with ], it may cause bleeding.<ref name="gale">{{Cite book|author=Longe JL|title=Gale Encyclopedia Of Cancer: A Guide To Cancer And Its Treatments|publisher=Thomson Gale|location=Detroit|year=2002|pages=|isbn=978-1-4144-0362-5|url-access=registration|url=https://archive.org/details/galeencyclopedia0000unse_b0o7/page/397}}</ref>
	==External links ==
	*
			==Pharmacology==
			===Mechanism of action===
			Etoposide forms a ternary complex with ] and the ] enzyme, which is an enzyme that aids in relaxing negative or positive ]s in DNA. Topoisomerase II normally will form a double-stranded break in one DNA double-strand, allow another to pass through, and ] the broken strands. Etoposide's binding prevents topoisomerase II from ] the broken DNA strands, which causes the DNA breaks made by topoisomerase II to stay broken, and also prevents the topoisomerase II molecule from leaving the site and relieving tension elsewhere. This results in a double-strand break in the DNA that can have various deleterious effects on the cell, and depletion of topoisomerase II available to relieve further tension.<ref name="pmid20534341">{{cite journal|vauthors=Pommier Y, Leo E, Zhang H, Marchand C|title = DNA topoisomerases and their poisoning by anticancer and antibacterial drugs|journal = Chem. Biol.|volume = 17|issue = 5|pages = 421–33|year = 2010|pmid = 20534341|doi = 10.1016/j.chembiol.2010.04.012|pmc = 7316379|doi-access = free}}</ref> ] cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in ] and promotes ] of the cancer cell.<ref name="wow"/><ref>{{cite journal|vauthors=Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA|title=Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives|journal=Toxicon|volume=44|issue=4|pages=441–59|year=2004|doi=10.1016/j.toxicon.2004.05.008|pmid=15302526|bibcode=2004Txcn...44..441G }}</ref>
			==Chemistry==
			] (or "American mandrake"), showing part of the ] (at bottom)]]
			Etoposide is a ] derivative of ] from the ] of the ] (or "American mandrake", ''Podophyllum peltatum''). More specifically, it is a ] of podophyllotoxin with a <small>D</small>-] derivative. It is chemically similar to the anti-cancer drug ], being distinguished only by a ] group where teniposide has a ].<ref name="Mutschler">{{Cite book|vauthors = Mutschler E, Schäfer-Korting M|title=Arzneimittelwirkungen|language=de|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2001|edition=8th|pages=894–5|isbn=3-8047-1763-2}}</ref> Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.<ref name="Dinnendahl">{{cite book|title=Arzneistoff-Profile|veditors = Dinnendahl V, Fricke U|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|date=2015|edition=28th|volume=4|isbn=978-3-7741-9846-3|language=de}}</ref>
			The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents.<ref name="Dinnendahl"/>
			It is used in form of its ] etoposide phosphate.
			==History==
			Etoposide was first synthesized in 1966 and U.S. ] approval was granted in 1983.<ref name="wow">{{cite journal|author = Hande KR|title = Etoposide: four decades of development of a topoisomerase II inhibitor|journal = Eur. J. Cancer|volume = 34|issue = 10|pages = 1514–21|year = 1998|pmid = 9893622|doi = 10.1016/S0959-8049(98)00228-7}}</ref>
			The nickname VP-16 likely comes from a compounding of the last name of one of the chemists who performed early work on the drug (von Wartburg) and podophyllotoxin.<ref>{{cite journal|vauthors=Kuhn M, Von Wartburg A|title=''Podophyllum''-Lignane: Struktur und Absolutkonfiguration von Podorhizol-β-D-glucosid ( = Lignan F). 19. Mitt. über mitosehemmende Naturstoffe<nowiki></nowiki>|journal=Helvetica Chimica Acta|volume=50|issue=6|pages=1546–65|year=1967|doi=10.1002/hlca.19670500614|url=http://www3.interscience.wiley.com/journal/109731280/abstract|archive-url=https://archive.today/20130105071517/http://www3.interscience.wiley.com/journal/109731280/abstract|url-status=dead|archive-date=2013-01-05}}</ref> Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist ].
	==References ==		==References ==
			{{reflist}}
	<references/>
			==External links ==
			*{{cite web|url = https://druginfo.nlm.nih.gov/drugportal/name/etoposide|publisher = U.S. National Library of Medicine|work = Drug Information Portal|title = Etoposide}}
			*{{cite web|url = https://druginfo.nlm.nih.gov/drugportal/name/etoposide%20phosphate|publisher = U.S. National Library of Medicine|work = Drug Information Portal|title = Etoposide phosphate}}
			*{{cite web|title=Etoposide|website=National Cancer Institute|date=12 August 2008|url=https://www.cancer.gov/about-cancer/treatment/drugs/etoposide}}
			*{{cite web|title=Etoposide|work=NCI Drug Dictionary|publisher=National Cancer Institute|url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/etoposide}}
	{{Chemotherapeutic agents}}		{{Chemotherapeutic agents}}
			{{portal bar|Medicine}}
	]		]
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