| Revision as of 13:28, 15 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'UNII').← Previous edit |
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{{Short description|Pharmaceutical drug}} |
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{{Use dmy dates|date=June 2024}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{drugbox |
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{{drugbox |
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| IUPAC_name = |
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| Watchedfields = changed |
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| verifiedrevid = 460773610 |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| Drugs.com = {{drugs.com|monograph|darbepoetin_alfa}} |
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| Drugs.com = {{drugs.com|monograph|darbepoetin_alfa}} |
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| MedlinePlus = a604022 |
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| MedlinePlus = a604022 |
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| DailyMedID = Darbepoetin alfa |
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| licence_EU = Aranesp |
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| pregnancy_AU = B3 |
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| licence_US = Darbepoetin_alfa |
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| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Darbepoetin alfa (Aranesp) Use During Pregnancy | website=Drugs.com | date=31 December 2018 | url=https://www.drugs.com/pregnancy/darbepoetin-alfa.html | access-date=7 April 2020}}</ref> |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_status = |
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| routes_of_administration = |
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| routes_of_administration = ], ] |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| elimination_half-life = |
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<!--Identifiers--> |
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| CAS_number = 11096-26-7 |
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| ATC_prefix = B03 |
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| ATC_prefix = B03 |
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| ATC_suffix = XA02 |
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| ATC_suffix = XA02 |
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| ATC_supplemental = |
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| ATC_supplemental = |
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| PubChem = |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = |
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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 = |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref>{{cite web | website=European Medicines Agency | title=Aranesp EPAR | date=8 June 2001 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/aranesp | access-date=29 June 2024}}</ref> |
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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 = Rx-only |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| elimination_half-life = |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|changed|CAS}} |
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| CAS_number = 209810-58-2 |
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| PubChem = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00012 |
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| DrugBank = DB00012 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = <!-- blanked - oldvalue: 15UQ94PT4P --> |
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| UNII = 15UQ94PT4P |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = NA |
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| ChemSpiderID = none |
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<!--Chemical data--> |
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<!-- Chemical data --> |
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| C=815 | H=1317 | N=233 | O=241 | S=5 |
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| C=815 | H=1317 | N=233 | O=241 | S=5 |
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| molecular_weight = 18396.1 g/mol |
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}} |
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}} |
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'''Darbepoetin alfa''' (]) ({{IPAc-en|icon|d|ɑr|b|ə|ˈ|p|ɔɪ|t|ɨ|n}}) is a synthetic form of ]. It stimulates ] (increases ] levels) and is used to treat ], commonly associated with ] and cancer ]. Darbepoetin is marketed by ] under the trade name '''Aranesp'''. |
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'''Darbepoetin alfa''' (]) {{IPAc-en|d|ɑːr|b|ə|ˈ|p|oʊ|ᵻ|t|ᵻ|n}} is a re-engineered form of ] containing 5 amino acid changes (N30, T32, V87, N88, T90) resulting in the creation of 2 new sites for N-linked carbohydrate addition. It has a 3-fold longer serum half-life compared to epoetin alpha and epoetin beta. It stimulates ] (increases ] levels) by the same mechanism as rHuEpo (binding and activating the Epo receptor) and is used to treat ], commonly associated with ] and cancer ]. Darbepoetin is marketed by ] under the trade name '''Aranesp'''. |
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The drug was approved in September 2001 by the ] for treatment of anemia in patients with chronic renal failure by intravenous or subcutaneous injection.<ref>{{cite web |url=http://www.fda.gov/cder/foi/appletter/2001/darbamg091701L.htm |
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The medication was approved in September 2001, by the US ] for treatment of anemia in patients with chronic kidney failure by intravenous or subcutaneous injection.<ref>{{cite web |url= https://www.fda.gov/cder/foi/appletter/2001/darbamg091701L.htm |title=Product Approval Information - Licensing Action |access-date=27 January 2007 | vauthors = Siegel JP |date=17 September 2001 |publisher=United States Food and Drug Administration |archive-url= https://web.archive.org/web/20061022234117/https://www.fda.gov/cder/foi/appletter/2001/darbamg091701L.htm |archive-date=22 October 2006 |url-status=dead }}</ref> In June 2001, it had been approved by the ] for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy.<ref>{{cite web |url= http://www.emea.europa.eu/humandocs/PDFs/EPAR/aranesp/129901en1.pdf |title=European Public Assessment Report (Abstract) |access-date=27 January 2007 |date=8 June 2001 |publisher=European Medicines Agency |url-status=dead |archive-url=https://web.archive.org/web/20061017113846/http://emea.europa.eu/humandocs/PDFs/EPAR/aranesp/129901en1.pdf |archive-date=17 October 2006 }}</ref> |
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|title=Product Approval Information - Licensing Action |accessdate=2007-01-27 |author=Jay P. Siegel |
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|date=2001-09-17 |publisher=United States Food and Drug Administration |archiveurl = http://web.archive.org/web/20061022234117/http://www.fda.gov/cder/foi/appletter/2001/darbamg091701L.htm <!-- Bot retrieved archive --> |archivedate = 2006-10-22}}</ref> In June 2001, it had been approved by the ] for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy.<ref>{{cite web |url=http://www.emea.europa.eu/humandocs/PDFs/EPAR/aranesp/129901en1.pdf |
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|title=European Public Assessment Report (Abstract) |accessdate=2007-01-27 |date=2001-06-08 |
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|format=PDF |publisher=European Medicines Agency}}</ref> |
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Dr Reddy’s Laboratories has launched darbepoetin alfa in India under the brand name ‘Cresp’ in August 2010. This is the world’s first generic darbepoetin alfa. Cresp has been approved in India. |
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] launched darbepoetin alfa in India under the brand name Cresp in August 2010. This is the world's first follow-on biologic of darbepoetin alfa. |
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Darbepoetin is produced by ] technology in modified ]s.{{cn|date=October 2011}} It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-] ]. |
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Darbepoetin is produced by ] technology in modified ]s.<ref>{{cite journal | vauthors = Smith RE, Jaiyesimi IA, Meza LA, Tchekmedyian NS, Chan D, Griffith H, Brosman S, Bukowski R, Murdoch M, Rarick M, Saven A, Colowick AB, Fleishman A, Gayko U, Glaspy J | title = Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer | journal = British Journal of Cancer | volume = 84 | issue = Suppl 1 | pages = 24–30 | date = April 2001 | pmid = 11308271 | pmc = 2363901 | doi = 10.1054/bjoc.2001.1749 }}</ref> It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-] ]. |
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It is on the ].<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> |
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Like EPO, its use increases the risk of cardiovascular problems, including ], arrhythmia, ] and ], congestive heart failure, ] or ischemia, ] and edema. Also seizures and strokes. A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy).<ref>{{cite news |first=Andrew |last=Pollack |
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|title=Amgen Finds Anemia Drug Holds Risks in Cancer Use |
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|url=http://www.nytimes.com/2007/01/26/business/26amgen.html?th&emc=th |
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|publisher=The New York Times |date=2007-01-26 |accessdate=2007-01-27 }}</ref> Pre-existing untreated hypertension is a contra-indication for darbepoetin, as well as some hematologic diseases. Other reported adverse reactions include ], ], chest pains, nausea and ]. |
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==Contraindications== |
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Like EPO, it has the potential to be abused by athletes seeking a competitive advantage. Its use during the ] to improve performance led to the disqualification of ] ] and ] of Russia and ] of Spain from their final races. Nevertheless, recent publication in professional literature indicate that the detection of prohibited substances at the 2002 Olympics may have been false as a result of less-than-perfect detection methodology, and the Olympic champions could therefore wrongly suffer IOC sanctions.<ref>{{cite web |first=AR |last=Koudinov |title=WADA, IOC Testing For Erythropoietin Is Faked |url=http://dopingjournal.org/content/3/1/dopingj022006-01.html |publisher=The Doping Journal |date=2006-02-26 |accessdate=2008-07-29 |work=}}</ref> |
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Use of darbepoetin alfa is contraindicated in patients with hypersensitivity to the drug, pre-existing uncontrolled hypertension, and pure red cell aplasia.<ref name="Lexi">"Darbepoetin Alfa (Lexi-Drugs)". LexiComp. Retrieved 29 October 2014.</ref> |
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==Adverse effects== |
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Darbepoetin alfa has ] in the United States for increased risk of ], ], ], ], ] of vascular access, and ] progression or recurrence. To avoid side effects, it is recommended for patients with chronic kidney failure or cancer to use the lowest possible dose needed to avoid red blood cell (RBC) ].<ref name="Aranesp FDA label">{{cite web | title=Aranesp- darbepoetin alfa injection, solution Aranesp- darbepoetin alfa solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fd36cb9-c4f6-4167-93c9-8530865db3f9 | access-date=7 April 2020}}</ref> |
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In addition to those listed in the black box warning, use of darbepoetin alfa also increases the risk of cardiovascular problems, including ], arrhythmia, ] and ], and ].<ref name="Lexi"/> A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy).<ref>{{cite news | vauthors = Pollack A | title=Amgen Finds Anemia Drug Holds Risks in Cancer Use | url=https://www.nytimes.com/2007/01/26/business/26amgen.html?th&emc=th | newspaper=The New York Times |date=26 January 2007 |access-date=27 January 2007 }}</ref>{{medcn|date=February 2015}} Other reported adverse reactions include increased risk of ], ], and chest pain.<ref>{{cite book | vauthors = Vest LS, Patel P, Patel JB | chapter = Epoetin Alfa | date = June 2024 | title = StatPearls . | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 32119434 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK554547/}}</ref> |
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==Pregnancy and lactation== |
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Darbepoetin alfa is not assigned a pregnancy category in the United States.<ref name="Drugs.com pregnancy" /> |
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It is not known if darbepoetin alfa is excreted in breast milk.<ref name="Aranesp FDA label" /><ref name="Drugs.com pregnancy" /> |
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==Mechanism of action== |
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Darbepoetin alfa binds to the ] on ], stimulating RBC production and differentiation.<ref name="Lexi"/> |
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==Safety advisories in anemic cancer patients== |
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==Safety advisories in anemic cancer patients== |
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Amgen sent a "dear doctor" letter in January, 2007, that highlighted results from a recent anemia of cancer trial, and warned doctors to consider use in that{{Clarify|date=August 2009}} off-label indication with caution. |
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Amgen sent a "dear stockholders" letter in January 2007, that highlighted results from a recent anemia of cancer trial, and warned doctors to consider use in that off-label indication with caution.<ref>{{Cite web|last=Amgen|date=2007|title=Amgen 2007 Annual Report and Financial Summary|url=https://investors.amgen.com/static-files/5a4e76cb-55c8-48ff-b1a1-f4098e7f6d74|access-date=24 January 2022|archive-date=24 January 2022|archive-url=https://web.archive.org/web/20220124122903/https://investors.amgen.com/static-files/5a4e76cb-55c8-48ff-b1a1-f4098e7f6d74|url-status=dead}}</ref> |
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Amgen advised the U.S. Food and Drug Administration (FDA) as to the results of the DAHANCA 10 clinical trial. The DAHANCA 10 data monitoring committee found that 3-year loco-regional control in subjects treated with Aranesp was significantly worse than for those not receiving Aranesp (p=0.01). |
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Amgen advised the U.S. ] (FDA) as to the results of the ] 10 clinical trial. The DAHANCA 10 data monitoring committee found that 3-year loco-regional control in subjects treated with Aranesp was significantly worse than for those not receiving Aranesp (p=0.01).<ref>{{cite journal | vauthors = Wauters I, Pat K, Vansteenkiste J | title = Flexible dosing with Darbepoetin alfa for the treatment of chemotherapy-induced anemia | journal = Therapeutics and Clinical Risk Management | volume = 2 | issue = 2 | pages = 175–186 | date = June 2006 | doi = 10.2147/tcrm.2006.2.2.175 | doi-access = free | pmid = 18360591 | pmc = 1661657 }}</ref> |
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In response to these advisories, the FDA released a ]<ref>{{cite web |url=http://www.fda.gov/cder/drug/advisory/RHE2007.htm |title=FDA Public Health Advisory: Erythropoiesis-Stimulating Agents (ESAs): Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp) |accessdate=2007-06-05 |work= |archiveurl = http://web.archive.org/web/20070528103823/http://www.fda.gov/cder/drug/advisory/RHE2007.htm <!-- Bot retrieved archive --> |archivedate = 2007-05-28}}</ref> |
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In response to these advisories, the FDA released a ]<ref>{{cite web|url=https://www.fda.gov/cder/drug/advisory/RHE2007.htm |title=FDA Public Health Advisory: Erythropoiesis-Stimulating Agents (ESAs): Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp) |website=] |access-date=5 June 2007 |archive-url=https://web.archive.org/web/20070528103823/https://www.fda.gov/cder/drug/advisory/RHE2007.htm |archive-date=28 May 2007 |url-status=dead }}</ref> |
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on March 9, 2007, and a clinical ]<ref>{{cite web |url=http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.htm |title=Information for Healthcare Professionals: Erythropoiesis Stimulating Agents (ESA) |accessdate=2007-06-05 |work= |archiveurl = http://web.archive.org/web/20070515034509/http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.htm <!-- Bot retrieved archive --> |archivedate = 2007-05-15}}</ref> for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as ] and darbepoetin. The advisory recommended caution in using these agents in cancer patients receiving chemotherapy or off chemotherapy, and indicated a lack of clinical evidence to support improvements in quality of life or transfusion requirements in these settings. |
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on 9 March 2007, and a clinical alert<ref>{{cite web|url=https://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.htm |title=Information for Healthcare Professionals: Erythropoiesis Stimulating Agents (ESA) |website=] |access-date=5 June 2007 |archive-url=https://web.archive.org/web/20070515034509/https://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.htm |archive-date=15 May 2007 |url-status=dead }}</ref> for doctors on 16 February 2007, about the use of ] such as ] (marketed as Epogen) and darbepoetin alfa. The advisory recommended caution in using these agents in cancer patients receiving chemotherapy or off chemotherapy, and indicated a lack of clinical evidence to support improvements in quality of life or transfusion requirements in these settings. |
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According to the 2010 update to clinical practice guidelines from the ] (ASCO) and the ] (ASH), use of ESAs such as darbepoetin alfa in cancer patients is appropriate when following stipulations outlined in FDA-approved labeling.<ref>{{cite journal | vauthors = Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, Bennett CL, Bohlius J, Evanchuk D, Goode MJ, Jakubowski AA, Regan DH, Somerfield MR | title = American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer | journal = Journal of Clinical Oncology | volume = 28 | issue = 33 | pages = 4996–5010 | date = November 2010 | pmid = 20975064 | pmc = 2988667 | doi = 10.1200/jco.2010.29.2201 | url = http://www.asco.org/quality-guidelines/asco-ash-clinical-practice-guideline-update-use-epoetin-and-darbepoetin-adult | url-status = dead | archive-url = https://web.archive.org/web/20141103190540/http://www.asco.org/quality-guidelines/asco-ash-clinical-practice-guideline-update-use-epoetin-and-darbepoetin-adult | archive-date = 3 November 2014 }}</ref> |
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In addition, on March 9, 2007, drug manufacturers agreed to new "black box" warnings about the safety of these drugs. On November 8, 2007, additional "black box" warnings were included on the aranesp label, at the request of the FDA. |
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==Society and culture== |
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On March 22, 2007, a congressional inquiry into the safety of erythropoeitic growth factors was reported in the news media. Manufacturers were asked to suspend drug rebate programs for physicians and to also suspend marketing the drugs to patients. |
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Like EPO, darbepoetin alfa has the potential to be abused by athletes seeking a competitive advantage. Its use during the ] to improve performance led to the disqualification of ] ] of Russia, ] of Russia and ] of Spain from their final races.<ref>{{cite news | vauthors = McGrath M, Portal G |title=New drugs give cheats the edge |url= http://news.bbc.co.uk/2/hi/science/nature/1789625.stm |access-date=3 November 2014 |work=BBC News Online |date=30 January 2002 }}</ref> |
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===Economics=== |
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==Business considerations for drug manufacturers== |
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Epogen and Darbepoetin alfa had more than $6 billion in combined sales in 2006. Procrit sales were about $3.2 billion in 2006. |
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Epogen and Aranesp had more than $6 billion in combined sales in 2006.<ref>{{Cite web |last=((staff-author)) |date=14 March 2007 |title=FDA to Study Amgen Drugs |url=https://labusinessjournal.com/news/fda-to-study-amgen-drugs/ |access-date=8 June 2024 |website=Los Angeles Business Journal |language=en-US}}</ref> Procrit sales were about $3.2 billion in 2006.<ref>{{dead link|date=July 2021|bot=medic}}{{cbignore|bot=medic}}</ref> |
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==References== |
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== References == |
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{{Reflist}} |
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<References/> |
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{{Antianemic preparations}} |
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{{Cytokine receptor modulators}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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{{DEFAULTSORT:Darbepoetin Alfa}} |
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{{DEFAULTSORT:Darbepoetin Alfa}} |
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