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| AHFS/Drugs.com | Monograph |
| MedlinePlus | a604022 |
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| Routes of administration | Intravenous,subcutaneous |
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| Chemical and physical data | |
| Formula | C815H1317N233O241S5 |
| Molar mass | 18396.19 g·mol−1 |
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Darbepoetin alfa (INN)/dɑːrbəˈpoʊɪtɪn/ is a re-engineered form oferythropoietin 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 stimulateserythropoiesis (increasesred blood cell levels) by the same mechanism as rHuEpo (binding and activating the Epo receptor) and is used to treatanemia, commonly associated withchronic kidney failure and cancerchemotherapy. Darbepoetin is marketed byAmgen under the trade nameAranesp.
The medication was approved in September 2001, by the USFood and Drug Administration for treatment of anemia in patients with chronic kidney failure by intravenous or subcutaneous injection.[4] In June 2001, it had been approved by theEuropean Medicines Agency for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy.[5]
Dr. Reddy's Laboratories 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.
Darbepoetin is produced byrecombinant DNA technology in modifiedChinese hamster ovary cells.[6] It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-amino acidprotein.
It is on theWorld Health Organization's List of Essential Medicines.[7]
Use of darbepoetin alfa is contraindicated in patients with hypersensitivity to the drug, pre-existing uncontrolled hypertension, and pure red cell aplasia.[8]
Darbepoetin alfa hasblack box warnings in the United States for increased risk ofdeath,myocardial infarction,stroke,venous thromboembolism,thrombosis of vascular access, andtumor 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)transfusions.[9]
In addition to those listed in the black box warning, use of darbepoetin alfa also increases the risk of cardiovascular problems, includingcardiac arrest, arrhythmia,hypertension andcongestive heart failure, andedema.[8] A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy).[10][medical citation needed] Other reported adverse reactions include increased risk ofseizure,hypotension, and chest pain.[11]
Darbepoetin alfa is not assigned a pregnancy category in the United States.[1]
It is not known if darbepoetin alfa is excreted in breast milk.[9][1]
Darbepoetin alfa binds to theerythropoietin receptor onerythroid progenitor cells, stimulating RBC production and differentiation.[8]
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.[12]
Amgen advised the U.S.Food and Drug Administration (FDA) as to the results of theDAHANCA 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).[13]
In response to these advisories, the FDA released aPublic Health Advisory[14]on 9 March 2007, and a clinical alert[15] for doctors on 16 February 2007, about the use oferythropoeisis-stimulating agents (ESAs) such asepoetin alfa (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.
According to the 2010 update to clinical practice guidelines from theAmerican Society of Clinical Oncology (ASCO) and theAmerican Society of Hematology (ASH), use of ESAs such as darbepoetin alfa in cancer patients is appropriate when following stipulations outlined in FDA-approved labeling.[16]
Like EPO, darbepoetin alfa has the potential to be abused by athletes seeking a competitive advantage. Its use during the2002 Winter Olympic Games to improve performance led to the disqualification ofcross-country skiersLarisa Lazutina of Russia,Olga Danilova of Russia andJohann Mühlegg of Spain from their final races.[17]
Epogen and Aranesp had more than $6 billion in combined sales in 2006.[18] Procrit sales were about $3.2 billion in 2006.[19]
