Darbepoetin alfa (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

) is a re-engineered form of

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...

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

erythropoiesis Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is s ...

(increases

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

levels) by the same mechanism as rHuEpo (binding and activating the Epo receptor) and is used to treat

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

, commonly associated with

chronic kidney failure Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

and cancer

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

. Darbepoetin is marketed by

Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical Corporation, company headquartered in Thousand Oaks, California. As one of the world's largest independent biotechnology companies, Amgen has a ...

under the trade name Aranesp. The medication was approved in September 2001, by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

for treatment of anemia in patients with chronic kidney failure by intravenous or subcutaneous injection. In June 2001, it had been approved by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy.

Dr. Reddy's Laboratories Dr. Reddy's Laboratories Ltd. is an Indian multinational Pharmaceutical industry, pharmaceutical company based in Hyderabad. The company was founded by Kallam Anji Reddy, who previously worked in the mentor institute Indian Drugs and Pharmace ...

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 by

recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...

technology in modified

Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are a family of immortalized cell lines derived from epithelial cells of the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therap ...

s. It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Contraindications

Use of darbepoetin alfa is contraindicated in patients with hypersensitivity to the drug, pre-existing uncontrolled hypertension, and pure red cell aplasia."Darbepoetin Alfa (Lexi-Drugs)". LexiComp. Retrieved 29 October 2014.

Adverse effects

Darbepoetin alfa has black box warnings in the United States for increased risk of

death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

venous thromboembolism Venous thrombosis is the blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off ( embolizes) and flows to the lun ...

thrombosis Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...

of vascular access, and

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

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. In addition to those listed in the black box warning, use of darbepoetin alfa also increases the risk of cardiovascular problems, including

cardiac arrest Cardiac arrest (also known as sudden cardiac arrest CA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly Circulatory system, circulate around the body and the blood flow to the ...

, arrhythmia,

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

and

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

, and

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

. A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy). Other reported adverse reactions include increased risk of

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

, and chest pain.

Pregnancy and lactation

Darbepoetin alfa is not assigned a pregnancy category in the United States. It is not known if darbepoetin alfa is excreted in breast milk.

Mechanism of action

Darbepoetin alfa binds to the

erythropoietin receptor The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the ''EPOR'' gene. EpoR is a 52 kDa peptide with a single carbohydrate chain resulting in an approximately 56–57 kDa protein found on the surface of EPO res ...

on erythroid progenitor cells, stimulating RBC production and differentiation.

Safety advisories in anemic cancer patients

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. Amgen advised the U.S.

(FDA) as to the results of the

DAHANCA The Danish Head and Neck Cancer (DAHANCA) group was established in 1976 as a working group by the Danish Society for Head and Neck Oncology with the primary aim to develop national guidelines for the treatment of head and neck cancer Head and ne ...

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 on 9 March 2007, and a clinical alert for doctors on 16 February 2007, about the use of erythropoeisis-stimulating agents (ESAs) such as

epoetin alfa Epoetin alfa, sold under the brand name Epogen among others, is a human erythropoietin produced in cell culture using recombinant DNA technology. Epoetin alfa is an erythropoiesis-stimulating agent. It stimulates erythropoiesis (increasing red ...

(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 the

American Society of Clinical Oncology The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...

(ASCO) and the

American Society of Hematology The American Society of Hematology (ASH) is a professional organization representing hematologists, founded in 1958. Its annual meeting is held in December of every year and has attracted more than 30,000 attendees. The society publishes the medi ...

(ASH), use of ESAs such as darbepoetin alfa in cancer patients is appropriate when following stipulations outlined in FDA-approved labeling.

Society and culture

Like EPO, darbepoetin alfa has the potential to be abused by athletes seeking a competitive advantage. Its use during the 2002 Winter Olympic Games to improve performance led to the disqualification of cross-country skiers

Larisa Lazutina Larisa Yevgenyevna Lazutina (; née Ptitsyna, born 1 June 1965) is a Soviet-Russian former professional cross-country skier. Career Lazutina was awarded the Holmenkollen medal in 1998 (shared with Fred Børre Lundberg, Alexey Prokurorov and ...

of Russia, Olga Danilova of Russia and

Johann Mühlegg Johann Mühlegg (born 8 November 1970 in Marktoberdorf, Germany) is a former top level cross-country skier who competed in international competitions first representing Germany and then Spain, after becoming a Spanish citizen in 1999. He was excl ...

of Spain from their final races.

Economics

Epogen and Aranesp had more than $6 billion in combined sales in 2006. Procrit sales were about $3.2 billion in 2006.
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References

{{DEFAULTSORT:Darbepoetin Alfa Antianemic preparations Growth factors Erythropoiesis-stimulating agents Orphan drugs