Darbepoetin alfa
40592
221272609
2008-06-23T20:18:41Z
Rjwilmsi
203434
gen fixes + format *date= in cite news/web/paper templates - full explanation [[User:Rjwilmsi#My_correction_of_dates_in_templates|here]] using [[Project:AutoWikiBrowser|AWB]]
{{drugbox
| IUPAC_name =
| image =
| CAS_number = 11096-26-7
| ATC_prefix = B03
| ATC_suffix = XA02
| ATC_supplemental =
| PubChem =
| DrugBank = BTD00032
| C=815 | H=1317 | N=233 | O=241 | S=5
| molecular_weight = 18396.1 g/mol
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| pregnancy_category =
| legal_status =
| routes_of_administration =
| licence_EU =Aranesp
| licence_US =Darbepoetin_alfa
}}
'''Darbepoetin alfa''' ([[International Nonproprietary Name|rINN]]) ({{pronEng|dɑrbəˈpɔɪtɨn}}) is a synthetic form of [[erythropoietin]]. It stimulates [[erythropoiesis]] (increases [[red blood cell]] levels) and is used to treat [[anemia]], commonly associated with [[chronic renal failure]] and cancer [[chemotherapy]]. Darbepoetin is marketed by [[Amgen]] under the trade name '''Aranesp'''.
It was approved in September 2001 by the [[Food and Drug Administration]] 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
|title=Product Approval Information - Licensing Action |accessdate=2007-01-27 |author=Jay P. Siegel
|date=2001-09-17 |publisher=United States Food and Drug Administration}}</ref> In June 2001, it had been approved by the [[European Medicines Agency]] 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) |accessdate=2007-01-27 |date=2001-06-08
|format=PDF |publisher=European Medicines Agency}}</ref>
It is produced by [[recombinant DNA]] technology in modified [[Chinese hamster ovary cell]]s. It differs from endogenous erythropoietin by containing two more N-linked oligosaccharide chains. It is an erythropoiesis stimulating 165-[[amino acid]] [[protein]].
Like EPO its use increases the risk of cardiovascular problems, including [[cardiac arrest]], seizures, arrhythmia or strokes, [[hypertension]] and [[hypertensive encephalopathy]], congestive heart failure, [[vascular thrombosis]] or ischemia, [[myocardial infarction]] and edema. 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
|title=Amgen Finds Anemia Drug Holds Risks in Cancer Use
|url=http://www.nytimes.com/2007/01/26/business/26amgen.html?th&emc=th
|publisher=The New York Times |date=2007-01-26 |accessdate=2007-01-27 }}</ref> Pre-existing hypertension contra-indicates the use of darbepoetin as does existing a hematologic disease. Adverse reactions can include [[hypotension]], [[fever]], chest pains, nausea and [[myalgia]].
Also like EPO it has the potential to be abused by athletes seeking an advantage. Its use during the [[2002 Winter Olympic Games]] to improve performance led to the disqualification of [[cross-country skiing|cross-country skiers]] [[Larisa Lazutina]] and [[Olga Danilova]] of Russia and [[Johann Mühlegg]] of Spain from their final races.
==Safety advisories in anemic cancer patients==
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 off-label indication with caution.
Amgen advised the [[United States]] [[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).
In response to these advisories, the [[FDA]] released a [[Public Health Advisory]]<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 |format= |work=}}</ref>
on March 9, 2007, and a clinical [[Alert]]<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 |format= |work=}}</ref> for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as [[epogen]] and [[darbepoeitin]]. 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.
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]].
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.
==Business considerations for drug manufacturers==
Epogen and Darbepoetin alfa had more than $6 billion in combined sales in 2006. Procrit sales were about $3.2 billion in 2006.
==References==
<References/>
[[Category:Drugs]]
[[Category:Growth factors]]
[[Category:Erythropoiesis-stimulating agents]]