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 accommo ...

) 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 the bo ...

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' "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 stimulated by decrea ...

(increases

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

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

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

, commonly associated with

chronic kidney failure Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...

and cancer

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

. Darbepoetin is marketed by

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

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 respon ...

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 medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

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

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

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 foun ...

technology in modified

Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have foun ...

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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

. 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 ...

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 irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

venous thromboembolism Venous thrombosis is 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 lungs to ...

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a 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 (thro ...

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 Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

. 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 is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...

, arrhythmia,

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

and

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, and

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

. 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 An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

, 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 52kDa peptide with a single carbohydrate chain resulting in an approximately 56-57 kDa protein found on the surface of EPO responding cells. ...

erythroid progenitor cells Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...

, 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 in Denmark. T ...

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 In public relations and communication science, publics are groups of individual people, and the public (a.k.a. the general public) is the totality of such groupings. This is a different concept to the sociological concept of the ''Öffentlichkei ...

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

epoetin alfa Epoetin alfa is a human erythropoietin produced in cell culture using recombinant DNA technology. Authorised by the European Medicines Agency on 28 August 2007, it stimulates erythropoiesis (increasing red blood cell levels) and is used to treat ...

(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. It was founded in 1958. Its annual meeting is held in December of every year and has attracted more than 30,000 attendees. The society publishes t ...

(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 The 2002 Winter Olympics, officially the XIX Olympic Winter Games and commonly known as Salt Lake 2002 ( arp, Niico'ooowu' 2002; Gosiute Shoshoni: ''Tit'-so-pi 2002''; nv, Sooléí 2002; Shoshoni: ''Soónkahni 2002''), was an internationa ...

to improve performance led to the disqualification of cross-country skiers

Larisa Lazutina Larisa Yevgenyevna Lazutina (russian: Лариса Евгеньевна Лазутина; née Ptitsyna, born 1 June 1965) is a Russian former professional cross-country skier. Career Lazutina was awarded the Holmenkollen medal in 1998 (shared ...

and

Olga Danilova Olga Valeryevna Danilova ( Russian: Ольга Валерьевна Данилова; born 10 June 1970 in Bugulma, Tatar ASSR) is a Russian cross-country skier who competed from 1991 until she was banned for using performance-enhancing drugs i ...

of Russia and

Johann Mühlegg Johann Mühlegg (born 8 November 1970 in Ostallgäu, 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 exclude ...

of Spain from their final races.

Economics

Epogen and Aranesp had more than $6 billion in combined sales in 200

Procrit sales were about $3.2 billion in 200

References

External links

* {{DEFAULTSORT:Darbepoetin Alfa Antianemic preparations Growth factors Erythropoiesis-stimulating agents World Anti-Doping Agency prohibited substances Orphan drugs