Darbepoetin alfa
Encyclopedia
Darbepoetin alfa (icon) 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.
The drug 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. 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.
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.
Darbepoetin is produced by recombinant DNA
technology in modified Chinese hamster ovary cell
s. It differs from endogenous erythropoietin (EPO) 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
, arrhythmia, hypertension
and hypertensive encephalopathy
, congestive heart failure
, vascular thrombosis or ischemia, myocardial infarction
, edema
, and stroke. It can also increase risk of seizures. A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy). Pre-existing untreated hypertension is a contra-indication for darbepoetin, as well as some hematologic diseases. Other reported adverse reactions include hypotension
, fever
, chest pains, nausea and myalgia
.
Like EPO, it 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
and Olga Danilova
of Russia and Johann Mühlegg
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.
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).
In response to these advisories, the FDA released a Public Health Advisory
on March 9, 2007, and a clinical Alert
for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as epogen 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.
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.
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
. It stimulates erythropoiesis
Erythropoiesis
Erythropoiesis is the process by which red blood cells are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin...
(increases red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
levels) and is used to treat anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, commonly associated with chronic renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
and cancer chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. Darbepoetin is marketed by Amgen
Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
under the trade name Aranesp.
The drug was approved in September 2001 by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for treatment of anemia in patients with chronic renal failure by intravenous or subcutaneous injection. In June 2001, it had been approved by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy.
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.
Darbepoetin is produced by recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
technology in modified Chinese hamster ovary cell
Chinese Hamster Ovary cell
Chinese hamster ovary cells are a cell line derived from the ovary of the Chinese hamster. They are often used in biological and medical research and commercially in the production of therapeutic proteins. They were introduced in the 1960s and grow as a cultured monolayer...
s. It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
.
Like EPO, its use increases the risk of cardiovascular problems, including cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, arrhythmia, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and hypertensive encephalopathy
Hypertensive encephalopathy
Hypertensive encephalopathy is a neurological dysfunction induced by malignant hypertension. The term "hypertensive encephalopathy" was introduced to describe this type of encephalopathy by Oppenheimer and Fishberg in 1928. It describes cerebral conditions, typically reversible, caused by sudden...
, congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, vascular thrombosis or ischemia, myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, and stroke. It can also increase risk of seizures. A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy). Pre-existing untreated hypertension is a contra-indication for darbepoetin, as well as some hematologic diseases. Other reported adverse reactions include hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, chest pains, nausea and myalgia
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
.
Like EPO, it 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
Cross-country skiing
Cross-country skiing is a winter sport in which participants propel themselves across snow-covered terrain using skis and poles...
Larisa Lazutina
Larisa Lazutina
Larisa Evgenevna Lazutina is a former professional cross country skier who competed for Russia during several Winter Olympic Games. In the 1998 Winter Olympics in Nagano, Japan, she won five medals in skiing events: three gold, a silver and a bronze...
and Olga Danilova
Olga Danilova
Olga Danilova is a Russian cross country skier who competed from 1991 until she was banned for using performance enhancing drugs in 2002...
of Russia and Johann Mühlegg
Johann Mühlegg
Johann Mühlegg is a Spanish top level cross-country skier who has competed in international competitions first representing Germany and then Spain, after becoming a Spanish citizen in 1999...
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.
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 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).
In response to these advisories, the FDA released a Public Health Advisory
on March 9, 2007, and a clinical Alert
Alert
To be alert is to be in a state of alertness.Alert or ALERT may also refer to:-Places:* Alert, Indiana, a community in the United States* Alert, Nunavut, Canada, the northernmost permanently inhabited place in the world...
for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as epogen 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.
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.