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Revision as of 00:34, 20 November 2011 editThe chemistds (talk | contribs)Extended confirmed users5,761 edits added PubchemID, CSID, (Std)InChI & (Std)InChIKey← Previous edit		Latest revision as of 06:37, 2 December 2024 edit undoCorundumconundrum (talk | contribs)187 edits →Adverse effects: more appropriate for a manual
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			{{Short description|Chemical compound}}
			{{cs1 config |name-list-style=vanc |display-authors=6}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Watchedfields = changed
	| verifiedrevid = 459531226		| verifiedrevid = 461512035
			| image = Bendamustine2DCSD.svg
⚫	| IUPAC_name = 4--1-methylbenzimidazol-2-yl]butanoic acid
	| image = Bendamustine.png
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename = Treanda, others
	| Drugs.com = {{drugs.com|CDI|bendamustine}}		| Drugs.com = {{drugs.com|monograph|bendamustine-hydrochloride}}
	| MedlinePlus = a608034		| MedlinePlus = a608034
	| licence_US = Treanda		| DailyMedID = Treanda
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
		⚫	| routes_of_administration = ]
	| pregnancy_US = D
		⚫	| ATC_prefix = L01
	| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
		⚫	| ATC_suffix = AA09
			| DrugBank = DB06769
			| legal_AU = S4
			| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2014 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 | access-date=10 April 2023 | archive-date=10 April 2023 | archive-url=https://web.archive.org/web/20230410065838/https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 | url-status=live }}</ref>
	| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->		| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
	| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->		| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
	| legal_US = Rx-only		| legal_US = Rx-only
⚫	| routes_of_administration = Intravenous infusion
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
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	| metabolism = ] to inactive metabolites. Two minor metabolites (M3 and M4) formed by ]		| metabolism = ] to inactive metabolites. Two minor metabolites (M3 and M4) formed by ]
	| elimination_half-life = 40&nbsp;min (bendamustine), 3&nbsp;h (M3), 30&nbsp;min (M4)		| elimination_half-life = 40&nbsp;min (bendamustine), 3&nbsp;h (M3), 30&nbsp;min (M4)
			| excretion = ~50% urinary, ~25% fecal <ref>{{cite journal | vauthors = Dubbelman AC, Rosing H, Darwish M, D'Andrea D, Bond M, Hellriegel E, Robertson P, Beijnen JH, Schellens JH | title = Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy | journal = Drugs in R&D | volume = 13 | issue = 1 | pages = 17–28 | date = March 2013 | pmid = 23322528 | pmc = 3627029 | doi = 10.1007/s40268-012-0001-5 }}</ref>
	| excretion = Mostly fecal
	<!--Identifiers-->		<!--Identifiers-->
			| IUPHAR_ligand = 7478
	| CAS_number_Ref = {{cascite|changed|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 16506-27-7		| CAS_number = 16506-27-7
⚫	| ATC_prefix = L01
⚫	| ATC_suffix = AA09
	| PubChem = 65628		| PubChem = 65628
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 9266D9P3PQ		| UNII = 9266D9P3PQ
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 487253		| ChEMBL = 487253
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| PubChem = 65628
	| ChemSpiderID = 59069		| ChemSpiderID = 59069
			| synonyms = SDX-105
⚫	| SMILES = ClCCN(c2ccc1c(nc(n1C)CCCC(=O)O)c2)CCCl
⚫	| InChI = 1/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23)
⚫	| InChIKey = YTKUWDBFDASYHO-UHFFFAOYAV
	| StdInChI = 1S/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23)
	| StdInChIKey = YTKUWDBFDASYHO-UHFFFAOYSA-N
	<!--Chemical data-->		<!--Chemical data-->
		⚫	| IUPAC_name = 4--1-methylbenzimidazol-2-yl]butanoic acid
	| C=16 | H=21 | Cl=2 | N=3 | O=2		| C=16 | H=21 | Cl=2 | N=3 | O=2
		⚫	| smiles = ClCCN(c2ccc1c(nc(n1C)CCCC(=O)O)c2)CCCl
	| molecular_weight = 358.262 g/mol
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
		⚫	| StdInChI = 1S/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23)
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
		⚫	| StdInChIKey = YTKUWDBFDASYHO-UHFFFAOYSA-N
	}}		}}
			<!-- Definition and symptoms -->
			'''Bendamustine''', sold under the brand name '''Treanda''' among others, is a ] used in the treatment of ] (CLL), ], and ].<ref name=AHFS2016/><ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=579|edition=69}}</ref> It is given by ].<ref name=AHFS2016/>
			<!-- Side effects and mechanism -->
	'''Bendamustine''' (], trade names '''Ribomustin''' and '''Treanda'''; also known as '''SDX-105''') is a ] used in the treatment of ]s (CLL)<ref>{{cite journal |author=Kath R, Blumenstengel K, Fricke HJ, Höffken K |title=Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia |journal=J. Cancer Res. Clin. Oncol. |volume=127 |issue=1 |pages=48–54 |year=2001 |month=January |pmid=11206271 |doi= 10.1007/s004320000180|url=http://link.springer.de/link/service/journals/00432/bibs/1127001/11270048.htm}}</ref> and ]s. It belongs to the family of drugs called ]s. It is also being studied for the treatment of ].<ref>{{cite journal |author=Bagchi S |title=Bendamustine for advanced sarcoma |journal=Lancet Oncol. |volume=8 |issue=8 |pages=674 |year=2007 |month=August |pmid=17726779 |doi= 10.1016/S1470-2045(07)70225-5|url=}}</ref>
			Common side effects include ], fever, nausea, ], loss of appetite, cough, and rash.<ref name=AHFS2016/> Other severe side effects include ] and increased risk of infection.<ref name=AHFS2016/> Use in ] is known to harm the baby.<ref name=AHFS2016/> Bendamustine is in the ]s family of medication.<ref name=AHFS2016/> It works by interfering with the function of ] and ].<ref name=AHFS2016/>
	==History==		<!-- History and culture -->
			Bendamustine was approved for medical use in the United States in 2008.<ref name=AHFS2016>{{cite web|title=Bendamustine Hydrochloride|url=https://www.drugs.com/monograph/bendamustine-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221013540/https://www.drugs.com/monograph/bendamustine-hydrochloride.html|archive-date=21 December 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><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It was originally made from ].<ref name=AHFS2016/>
		⚫	== Medical uses ==
⚫	Bendamustine was first synthesized in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic). It is a white, water soluble microcrystalline powder with amphoteric properties. Until 1990 it was available only in East Germany. East German investigators found that it was useful for treating ], ], ], ] and ].
			]
			One combination for stage III/IV relapsed or refractory indolent ]s and ] (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab.<ref name="Weide2007">{{cite journal | vauthors = Weide R, Hess G, Köppler H, Heymanns J, Thomalla J, Aldaoud A, Losem C, Schmitz S, Haak U, Huber C, Unterhalt M, Hiddemann W, Dreyling M | title = High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG) | journal = Leukemia & Lymphoma | volume = 48 | issue = 7 | pages = 1299–1306 | date = July 2007 | pmid = 17613757 | doi = 10.1080/10428190701361828 | s2cid = 2381354 }}</ref> In Germany in 2012 it has become the first line treatment of choice for indolent lymphoma.<ref>{{cite web | vauthors = Susman E | veditors = Zaleznik DF | url = http://www.medpagetoday.com/MeetingCoverage/ASHHematology/36418 | title = New Combo Replaces CHOP for Lymphoma | date = December 2012 | archive-url = https://web.archive.org/web/20140911002243/http://www.medpagetoday.com/MeetingCoverage/ASHHematology/36418 | archive-date=2014-09-11 | work = MedPageToday }}</ref> After trial results released in June 2012 showed that it more than doubled disease ] when given along with ]. The combination also left patients with fewer side effects than the older ] treatment.<ref>{{cite news | vauthors = Mundell EJ | work = U.S. News & World Report |url=http://health.usnews.com/health-news/news/articles/2012/06/03/rediscovered-lymphoma-drug-helps-double-survival-study |title='Rediscovered' Lymphoma Drug Helps Double Survival: Study |date=June 3, 2012 |url-status=live |archive-url=https://web.archive.org/web/20120712193314/http://health.usnews.com/health-news/news/articles/2012/06/03/rediscovered-lymphoma-drug-helps-double-survival-study |archive-date=July 12, 2012 }}</ref>
			==Adverse effects==
⚫	Bendamustine received its first marketing approval in Germany, which is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited, which it is indicated as a single-agent or in combination with other anti-cancer agents for indolent NHL, multiple myeloma, and CLL. SymBio Pharmaceuticals Ltd holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries.
		⚫	Common adverse reactions are typical for the class of ]s, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and ], as well as immunosuppression, anemia, and ].
			Notably, this drug has a low incidence of hair loss (]) unlike most other chemotherapy drugs.<ref>{{cite journal | vauthors = Tageja N, Nagi J | title = Bendamustine: something old, something new | journal = Cancer Chemotherapy and Pharmacology | volume = 66 | issue = 3 | pages = 413–423 | date = August 2010 | pmid = 20376452 | doi = 10.1007/s00280-010-1317-x | s2cid = 25605764 | url = https://repositorio.unal.edu.co/bitstream/unal/77735/1/1075654222.2020.pdf }}</ref>
		⚫	==Pharmacology==
⚫	In March 2008, ] received approval from the ] ] to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of CLL.<ref>{{cite web |url=http://www.cephalon.com/newsroom/news_reader.aspx?ID=1120688 |title=Cephalon press release - Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia |accessdate=2008-03-23 |format= |work= }}</ref>
		⚫	Bendamustine is a white, water-soluble microcrystalline powder with ] properties. It acts as an ] causing intra-strand and inter-strand cross-links between ] bases.
⚫	In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell ] (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. <ref>{{cite web |url=http://www.cephalon.com/media/news-releases/article/video-cephalon-receives-fda-approval-for-treanda-to-treat-patients-with-relapsed-indolent-non-hodgk/ |title=Cephalon press release -Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma |accessdate=2008-11-03 |format= |work= }}</ref>
		⚫	After intravenous infusion it is extensively metabolised in the ] by ]. More than 95% of the drug is bound to protein – primarily ]. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes. It is eliminated primarily through the ]s.
⚫	==Pharmacology==
			==History==
⚫	Betamustine acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases.
		⚫	Bendamustine was first made in 1963 by Ozegowski and Krebs in ] (the former German Democratic Republic).<ref>{{cite journal | title= Aminosäureantagonisten. III. ω--propion- bzw. -buttersäuren als potentielle Cytostatika | journal=Advanced Synthesis and Catalysis | date= June 1963 | doi=10.1002/prac.19630200310 | volume=20 | issue=3–4 | pages=178–186 | vauthors=Ozegowski W, Krebs D}}</ref> Until 1990 it was available only in East Germany. East German researchers found that it was useful for treating ], ], ], ] and ].
		⚫	Bendamustine received its first marketing approval in Germany, where it is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited. It is indicated as a single-agent or in combination with other anti-cancer agents for indolent ], multiple myeloma, and chronic lymphocytic leukemia. SymBio Pharmaceuticals Ltd. holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries.
⚫	After intravenous infusion it is extensively metabolised in the ] by ] p450. >95% of the drug is bound to protein - primarily ]. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes. It is eliminated primarily by the renal route.
		⚫	In March 2008, ] received approval from the ] ] to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of chronic lymphocytic leukemia.<ref>{{cite web |url=http://www.cephalon.com/newsroom/news_reader.aspx?ID=1120688 | work = Cephalon press release | title = Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia |access-date=2008-03-23 |url-status=dead |archive-url=https://web.archive.org/web/20080421212459/http://www.cephalon.com/newsroom/news_reader.aspx?ID=1120688 |archive-date=2008-04-21 }}</ref>
⚫	== Chemotherapeutic uses ==
		⚫	In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell non-Hodgkin's lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.<ref>{{cite web |url=http://www.cephalon.com/media/news-releases/article/video-cephalon-receives-fda-approval-for-treanda-to-treat-patients-with-relapsed-indolent-non-hodgk/ | work = Cephalon press release | title = Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma |access-date=2008-11-03 |url-status=dead |archive-url=https://web.archive.org/web/20081207010837/http://www.cephalon.com/media/news-releases/article/video-cephalon-receives-fda-approval-for-treanda-to-treat-patients-with-relapsed-indolent-non-hodgk/ |archive-date=2008-12-07 }}</ref>
	Bendamustine has been used both as sole therapy and in combination with other agents including ], ], ], ], ], ], ] and <sup>90</sup>Y-].
			==Research==
	One combination for stage III/IV relapsed or refractory indolent ]s and ] (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab.<ref name="Weide2007">{{cite journal |author=Weide R, Hess G, Köppler H, ''et al.'' |title=High anti–lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A muticenter phase II study of the German Low Grade Lymphoma Study Group (GLSG) |journal=Leuk. Lymphoma. |volume=48 |issue=7 |pages=1299–1306 |year=2007 |doi=10.1080/10428190701361828 |url=http://informahealthcare.com/doi/abs/10.1080/10428190701361828 |pmid=17613757}}</ref>
			It is also being studied for the treatment of ].<ref>{{cite journal | vauthors = Bagchi S | title = Bendamustine for advanced sarcoma | journal = The Lancet. Oncology | volume = 8 | issue = 8 | pages = 674 | date = August 2007 | pmid = 17726779 | doi = 10.1016/S1470-2045(07)70225-5 }}</ref> It is also being investigated in phase II trials for the non-cancer treatment of ].<ref>{{cite journal |journal = Blood | vauthors = Lagos GG, Lentzsch S, Comenzo RL, Zonder JA, Osman K, Gould J, Tsai WY, Pregja S, Reyna M, Raza S, Sanchorawala V |title=Long Term Follow up of Patients with Relapsed/Refractory Systemic Light Chain (AL) Amyloidosis Treated with Bendamustine and Dexamethasone in a Phase 2 Study |date=8 December 2017 |volume=130 (supplement 1)|pages=1838}}</ref>
	==Adverse effects==		== References ==
⚫	Common adverse reactions are typical for ], and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and ], as well as immunosuppression, anemia, and ].
	==References==
	{{Reflist}}		{{Reflist}}
	==External links==
	* intended for US patients
	{{Chemotherapeutic agents}}		{{Chemotherapeutic agents}}
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	]
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