| Revision as of 11:53, 24 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456791852 of page Melphalan for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 09:43, 19 August 2024 edit Qwerfjkl (talk | contribs)Extended confirmed users, Page movers, Rollbackers212,892 editsm Added 1 {{Bare URL PDF}} tag(s) using a script. For other recently-tagged pages with bare URLs, see Category:Articles with bare URLs for citations from August 2024 and Category:Articles with PDF format bare URLs for citations |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Use dmy dates|date=September 2019}} |
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{{Drugbox |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
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| verifiedrevid = 408589249 |
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| Watchedfields = changed |
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| IUPAC_name = 4-phenylalanine |
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| verifiedrevid = 462248349 |
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| image = Melphalan.svg |
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| image = Melphalan.svg |
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| width = 240 |
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| alt = |
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| image2 = Melphalan ball-and-stick.png |
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| alt2 = |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = Alkeran |
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| pronounce = |
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| tradename = Alkeran, Evomela, Phelinun, others |
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| Drugs.com = {{drugs.com|monograph|melphalan}} |
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| Drugs.com = {{drugs.com|monograph|melphalan}} |
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| MedlinePlus = a682220 |
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| MedlinePlus = a682220 |
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| DailyMedID = Melphalan |
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| pregnancy_AU = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = |
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| pregnancy_AU_comment = |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_status = Rx-only |
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| routes_of_administration = Oral, ] |
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| routes_of_administration = ], ], ] |
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| class = |
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| ATC_prefix = L01 |
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| ATC_suffix = AA03 |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Alkeran FDA label">{{cite web | title=Alkeran- melphalan tablet, film coated | website=DailyMed | date=18 November 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ff913271-0090-4832-a0fe-5154fe8f97b9 | access-date=23 April 2022}}</ref><ref name="Evomela FDA label" /><ref name="Hepzato FDA label">https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/201848s000lbl.pdf {{Bare URL PDF|date=August 2024}}</ref> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Phelinun EPAR" /> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = 25% to 89% |
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| bioavailability = 25–89% (By mouth) |
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| protein_bound = |
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| metabolism = hydrolysis |
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| metabolism = Hydrolysis to inactive metabolites |
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| metabolites = |
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| onset = |
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| elimination_half-life = 1.5 ± 0.8 hours |
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| elimination_half-life = 1.5 ± 0.8 hours |
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| duration_of_action = |
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| excretion = ], significantly metabolised |
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| excretion = ] (IV: 5.8–21.3%) |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 148-82-3 |
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| CAS_number = 148-82-3 |
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| ATC_prefix = L01 |
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| CAS_supplemental = |
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| ATC_suffix = AA03 |
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| PubChem = 460612 |
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| PubChem = 4053 |
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| IUPHAR_ligand = 7620 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB01042 |
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| DrugBank = DB01042 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00369 |
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| KEGG = D00369 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 28876 |
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| ChEBI = 28876 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 852 |
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| ChEMBL = 852 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = <small>(2''S'')-2-amino-3-<nowiki/>{4-phenyl}propanoic acid</small> |
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<!--Chemical data--> |
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<!-- Chemical and physical data --> |
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| IUPAC_name = 4--<small>L</small>-phenylalanine |
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| C=13 | H=18 | Cl=2 | N=2 | O=2 |
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| C=13 | H=18 | Cl=2 | N=2 | O=2 |
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| molecular_weight = 305.2 g/mol |
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| smiles = c1cc(ccc1C(C(=O)O)N)N(CCCl)CCCl |
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| SMILES = c1cc(ccc1C(C(=O)O)N)N(CCCl)CCCl |
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| InChI = 1/C13H18Cl2N2O2/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19/h1-4,12H,5-9,16H2,(H,18,19)/t12-/m0/s1 |
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| InChIKey = SGDBTWWWUNNDEQ-LBPRGKRZBM |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C13H18Cl2N2O2/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19/h1-4,12H,5-9,16H2,(H,18,19)/t12-/m0/s1 |
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| StdInChI = 1S/C13H18Cl2N2O2/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19/h1-4,12H,5-9,16H2,(H,18,19)/t12-/m0/s1 |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = SGDBTWWWUNNDEQ-LBPRGKRZSA-N |
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| StdInChIKey = SGDBTWWWUNNDEQ-LBPRGKRZSA-N |
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| density = |
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| synonyms = <small>2-amino-3-phenyl]-propanoic acid</small> |
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| density_notes = |
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| melting_point = |
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| solubility = |
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| specific_rotation = |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Melphalan''', sold under the brand name '''Alkeran''' among others, is a ] used to treat ]; ]; lymphoblastic and ]; childhood ]; ]; mammary ]; and ].<ref name="Alkeran FDA label" /><ref name="Evomela FDA label" /><ref name="Phelinun EPAR" /><ref name=AHFS2019/> It is taken ] or by ].<ref name=AHFS2019/> |
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<!-- Side effects and mechanism --> |
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Common side effects include nausea and ].<ref name=AHFS2019/> Other severe side effects may include ] and the development of other ].<ref name=AHFS2019/> Use during pregnancy may result in harm to the fetus.<ref>{{cite web |title=Melphalan Use During Pregnancy |url=https://www.drugs.com/pregnancy/melphalan.html |website=Drugs.com |access-date=9 October 2019}}</ref> Melphalan belongs to the class of ] ].<ref name=AHFS2019/> It works by interfering with the creation of ] and ].<ref name=AHFS2019/> |
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<!-- History and culture --> |
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Melphalan was approved for medical use in the United States in 1964.<ref name=AHFS2019>{{cite web |title=Melphalan Monograph for Professionals |url=https://www.drugs.com/monograph/melphalan.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=9 October 2019}}</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> It is available as a ].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=873–874|edition=76}}</ref> |
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== Medical uses == |
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In the European Union, melphalan is ] for the treatment of multiple myeloma; malignant lymphoma (Hodgkin, non-Hodgkin lymphoma); acute lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; and mammary adenocarcinoma.<ref name="Phelinun EPAR" /> |
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In the United States, melphalan is used as a high-dose ] treatment prior to ] in people with ].<ref name="Evomela FDA label">{{cite web | title=Evomela- melphalan injection, powder, lyophilized, for solution | website=DailyMed | date=31 December 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5d68b96-14bd-4605-b6d2-2bf8b0c5ca8a | access-date=23 April 2022}}</ref><ref>{{cite web | title=Evomela (Captisol-enabled melphalan HCl) for Injection | website=U.S. ] (FDA) | date=30 November 2016 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207155Orig1s000_Orig2s000TOC.cfm | access-date=7 September 2023}}</ref> In the European Union, it is indicated, in combination with other cytotoxic medicinal products, as reduced intensity conditioning treatment prior to allogeneic haematopoietic stem cell transplantation in malignant haematological diseases in adults.<ref name="Phelinun EPAR" /> |
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In August 2023, the US Food and Drug Administration approved melphalan (Hepzato) as a liver-directed treatment for adults with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.<ref>{{cite web | title=Oncology (Cancer) / Hematologic Malignancies Approval Notifications | website=U.S. ] (FDA) | date=14 August 2023 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications | access-date=7 September 2023}} {{PD-notice}}</ref><ref>{{cite press release | title=Delcath Systems, Inc. Announces FDA Approval of Hepzato Kit for the Treatment of Adult Patients with Unresectable Hepatic-Dominant Metastatic Uveal Melanoma | publisher=Delcath Systems | via=PR Newswire | date=14 August 2023 | url=https://www.prnewswire.com/news-releases/delcath-systems-inc-announces-fda-approval-of-hepzato-kit-for-the-treatment-of-adult-patients-with-unresectable-hepatic-dominant-metastatic-uveal-melanoma-301900346.html | access-date=7 September 2023}}</ref> |
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== Side effects == |
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Common side effects include:<ref name=AHFS2019/> |
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* ] |
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* ] suppression, including |
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** ] causing increased risk of ] |
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** ] causing increased risk of bleeding |
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Less common side effects include: |
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* Severe ]s<ref name=AHFS2019/> |
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* ] (scarring of lung tissue) including fatal outcomes (usually only with prolonged use) |
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* ] |
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* ] |
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* ] |
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* ] |
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* Irreversible bone marrow failure due to melphalan not being withdrawn early enough |
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* ] |
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== Mechanism of action == |
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Melphalan chemically alters the ] nucleotide ] through ], and causes linkages between strands of DNA. This chemical alteration inhibits ] and ], functions necessary for cells to survive. These changes cause ] in both dividing and non-dividing tumor cells.<ref>{{cite web|title=Melphalan|url=http://www.cancer.gov/drugdictionary?cdrid=42973|publisher=National Cancer Institute|access-date=4 August 2014}}</ref> |
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== Synthesis == |
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alanine|journal=Journal of the Chemical Society (Resumed)|pages=1223–1230|year=1955| vauthors = Bergel F, Burnop VC, Stock JA }}</ref><ref>{{Cite journal|doi=10.1016/S0140-6736(55)92736-7|pmid=13243678|title=Studies on the anti-tumour activity of p-di-(2-chloroethyl) aminophenylalanine (sarcolysine)|journal=Lancet|volume=266|issue=6882|pages=169–71|year=1955|vauthors=Larionov LF, Khokhlov AS, Shkodinskaja EN, Vasina OS, Troosheikina VI, Novikova MA }}</ref> {{US patent|3032584}}; {{US patent|3032585}} (both 1962 to ]).]] |
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4-Nitro-L-] ('''1''') was converted to its ] by heating with ], and this was converted to its ethyl ] ('''2'''). Catalytic hydrogenation produced the corresponding aniline. Heating in acid with ], followed by treatment with ] provided the bischloride, and removal of the protecting groups by heating in ] gave melphalan ('''3'''). |
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== Society and culture == |
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=== Legal status === |
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On 17 September 2020, the ] (CHMP) of the ] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for melphalan.<ref name="Phelinun: Pending EC decision">{{cite web | title=Phelinun: Pending EC decision | website=] (EMA) | date=18 September 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/phelinun | access-date=21 September 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The applicant for this medicinal product is Adienne S.r.l. S.U.<ref name="Phelinun: Pending EC decision" /> Melphalan was approved for medical use in the European Union in November 2020.<ref name="Phelinun EPAR">{{cite web | title=Phelinun EPAR | website=] (EMA) | date=15 September 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/phelinun | access-date=23 April 2022}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> |
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== References == |
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{{reflist}} |
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{{Chemotherapeutic agents}} |
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{{Nitrogen mustards}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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