AHFS/Drugs.com Monograph Pregnancy
category AU: B3 Molar mass 38,396.1 g/mol | MedlinePlus a604022 ATC code B03XA02 (WHO) | |
License data EU EMA: Aranesp
US FDA: Darbepoetin_alfa Legal status AU: S4 (Prescription only) | ||
Darbepoetin alfa (rINN) /dɑːrbəˈpɔɪtᵻn/ 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.
Contents
- Contraindications
- Adverse effects
- Pregnancy and lactation
- Mechanism of action
- Safety advisories in anemic cancer patients
- Society and culture
- Economics
- References
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 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 cells. It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-amino acid protein.
Contraindications
Use of darbepoetin alfa is contraindicated in patients with hypersensitivity to the drug, pre-existing uncontrolled hypertension, and pure red cell aplasia.
Adverse effects
Darbepoetin alfa has black box warnings in the United States for increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence. To avoid side effects, it is recommended for patients with chronic renal 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, arrhythmia, hypertension and congestive heart failure, and edema. 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, hypotension, and chest pain.
Pregnancy and lactation
Darbepoetin alfa is a Pregnancy Category C drug in the United States. Pregnant women who are taking darbepoetin alfa may enroll in Amgen’s Pregnancy Surveillance Program (800-772-6436).
It is not known if darbepoetin alfa is excreted in breast milk. Mothers who choose to breast-feed are advised to use caution.
Mechanism of action
Darbepoetin alfa binds to the erythropoietin receptor on erythroid progenitor cells, stimulating RBC production and differentiation.
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 for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents (ESAs) such as epoetin 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 the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (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 and Olga Danilova of Russia and Johann Mühlegg 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.