Epoetin alfa

Last updated

Epoetin alfa
Clinical data
Pronunciation /ɛˈpoʊ.ɪtɪn/
Trade names Epogen, Retacrit
Other namesepoetin alfa-epbx
AHFS/Drugs.com Monograph
MedlinePlus a692034
License data
Routes of
administration 		Intravenous, subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C815H1317N233O241S5
Molar mass 18396.19 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Epoetin alfa is a human erythropoietin produced in cell culture using recombinant DNA technology. [6] Authorised by the European Medicines Agency on 28 August 2007, it stimulates erythropoiesis (increasing red blood cell levels) and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy.

Contents

Epoetin is manufactured and marketed by Amgen under the brand name Epogen. Johnson & Johnson subsidiary Janssen Biotech (formerly Ortho Biotech Products, LP), sells the same drug under the name Procrit, pursuant to a product license agreement. The average cost per patient in the U.S. was $8,447 in 2009. [7] Darbepoetin alfa (rINN) /dɑːrbəˈpɔɪtɪn/ is a glycosylation analog of erythropoietin containing two additional N-linked carbohydrate chains, [8] also manufactured and marketed by Amgen, with a brand name of Aranesp. The Food and Drug Administration (FDA) warnings and safety precautions for Procrit, Epogen and Aranesp are identical.

For several years, epoetin alfa has accounted for the single greatest drug expenditure paid by the U.S. Medicare system; in 2010, the program paid $2 billion for the drug. [9] [10] Raising hemoglobin levels has been found in some studies to be associated with higher risks of thrombotic events, strokes and death. [11]

It is on the World Health Organization's List of Essential Medicines. [12]

Medical uses

Erythropoietin is available as a therapeutic agent produced by recombinant DNA technology in mammalian cell culture. It is used in treating anemia resulting from chronic kidney disease and myelodysplasia, from the treatment of cancer (chemotherapy and radiation).[ citation needed ]

Anemia caused by kidney disease

For people who require dialysis or have chronic kidney disease, iron should be given with erythropoietin, depending on some laboratory parameters such as ferritin and transferrin saturation. [13] Dialysis patients in the U.S. are most often given Epogen; other brands of epoetin may be used in other countries.[ citation needed ]

Erythropoietin is also used to treat anemia in people, and cats and dogs, with chronic kidney disease who are not on dialysis (those in Stage 3 or 4 disease and those living with a kidney transplant). There are two types of erythropoietin for people, and cats and dogs, with anemia due to chronic kidney disease (not on dialysis). [14] [15]

Anemia caused by cancer

In March 2008, a panel of advisers for the U.S. Food and Drug Administration (FDA) supported keeping erythropoiesis-stimulating agents (ESAs) produced by Amgen and Johnson & Johnson on the market for use in cancer patients. The FDA has focused its concern on study results from some clinical trials showing an increased risk of death and tumor growth in chemotherapy patients taking the anti-anemia drugs.[ citation needed ]

Anemia in critically ill people

Erythropoietin is used to treat people with anemia resulting from critical illness.

In a randomized controlled trial, [16] erythropoietin was shown to not change the number of blood transfusions required by critically ill patients. A surprising finding in this study was a small mortality reduction in patients receiving erythropoietin. This result was statistically significant after 29 days but not at 140 days. The mortality difference was most marked in patients admitted to the ICU for trauma. The authors provide several hypotheses for potential etiologies of this reduced mortality, but, given the known increase in thrombosis and increased benefit in trauma patients as well as marginal nonsignificant benefit (adjusted hazard ratio of 0.9) in surgery patients, it could be speculated that some of the benefit might be secondary to the procoagulant effect of erythropoietin. Regardless, this study suggests further research may be necessary to see which critical care patients, if any, might benefit from administration of erythropoietin. Any benefit of erythropoietin use must be weighed against the increased likelihood of thrombosis, which has been demonstrated in numerous trials.[ citation needed ]

Neurological diseases

Erythropoietin has been hypothesized to be beneficial in treating certain neurological diseases such as schizophrenia and stroke. [17] Some research has suggested that erythropoietin improves the survival rate in children with cerebral malaria, which is caused by the malaria parasite's blockage of blood vessels in the brain. [18] [19] [20] However, the possibility that erythropoietin may be neuroprotective is inconsistent with the poor transport of the chemical into the brain [21] and the low levels of erythropoietin receptors expressed on neuronal cells.

Psychiatric diseases

Randomized clinical control trials have shown promising results of EPO in improving cognition which is often intractable with the current treatment of mood disorders and schizophrenia.These domains include speed of complex cognitive processing across attention,memory and executive function. [22]

Preterm infants

Infants born early often require transfusions with red blood cells and have low levels of erythropoietin. Erythropoietin has been studied as a treatment option to reduce anemia in preterm infants. Treating infants less than 8 days old with erythropoietin may slightly reduce the need for red blood cell transfusions, but increases the risk of retinopathy. Due to the limited clinical benefit and increased risk of retinopathy, early or late erythropoietin treatment is not recommended for preterm infants. [23] [24]

Adverse effects

Epoetin alfa is generally well tolerated. Common side effects include high blood pressure, headache, disabling cluster migraine (resistant to remedies), joint pain, and clotting at the injection site. Rare cases of stinging at the injection site, skin rash, and flu-like symptoms (joint and muscle pain) have occurred within a few hours following administration. More serious side effects, including allergic reactions, seizures and thrombotic events (e.g., heart attacks, strokes, and pulmonary embolism) rarely occur. Chronic self-administration of the drug has been shown to cause increases in blood hemoglobin and hematocrit to abnormally high levels, resulting in dyspnea and abdominal pain. [25]

Erythropoietin is associated with an increased risk of adverse cardiovascular complications in patients with kidney disease if it is used to target an increase of hemoglobin levels above 13.0 g/dl. [26]

Early treatment (before an infant is 8 days old) with erythropoietin correlated with an increase in the risk of retinopathy of prematurity in premature and anemic infants, raising concern that the angiogenic actions of erythropoietin may exacerbate retinopathy. [23] [24] Since anemia itself increases the risk of retinopathy, the correlation with erythropoietin treatment may be incidental.[ citation needed ]

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.[ citation needed ]

Amgen advised the U.S. Food and Drug Administration (FDA) regarding the results of the DAHANCA 10 clinical trial. The DAHANCA 10 data monitoring committee found that three-year loco-regional cancer control in subjects treated with Aranesp was significantly worse than for those not receiving Aranesp (p=0.01).[ citation needed ]

In response to these advisories, the FDA released a Public Health Advisory [27] on 9 March 2007, and a clinical alert [28] for doctors on 16 February 2007, about the use of erythropoiesis-stimulating agents (ESAs) 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 9 March 2007, drug manufacturers agreed to new black box warnings about the safety of these drugs.

On 22 March 2007, a congressional inquiry into the safety of erythropoietic 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.

Several publications and FDA communications have increased the level of concern related to adverse effects of ESA therapy in selected groups. In a revised black box warning, the FDA notes significant risks, advising that ESAs should be used only in patients with cancer when treating anemia specifically caused by chemotherapy, and not for other causes of anemia. Further, the warning states that ESAs should be discontinued once the patient's chemotherapy course has been completed. [29] [30] [31] [32]

Interactions

Drug interactions with erythropoietin include:

Society and culture

The publication of an editorial questioning the benefits of high-dose epoetin was canceled by the marketing branch of a journal after being accepted by the editorial branch highlighting concerns of conflict of interest in publishing. [34]

In 2011, author Kathleen Sharp published a book, Blood Feud: The Man Who Blew the Whistle on One of the Deadliest Prescription Drugs Ever, [35] alleging drug maker Johnson & Johnson encouraged doctors to prescribe epoetin in high doses, particularly for cancer patients, because this would increase sales by hundreds of millions of dollars. Former sales representatives Mark Duxbury and Dean McClennan, claimed that the bulk of their business selling epoetin to hospitals and clinics was Medicare fraud, totaling US$3 billion. [36]

Biosimilars

In August 2007, Binocrit, Epoetin Alfa Hexal, and Abseamed were approved for use in the European Union. [37] [38] [4]

Related Research Articles

Darbepoetin alfa (INN) is a re-engineered form of erythropoietin containing 5 amino acid changes 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 by the same mechanism as rHuEpo and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy. Darbepoetin is marketed by Amgen under the trade name Aranesp.

<span class="mw-page-title-main">Myelodysplastic syndrome</span> Diverse collection of blood-related cancers

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

<span class="mw-page-title-main">Erythropoietin</span> Protein that stimulates red blood cell production

Erythropoietin, 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 bone marrow. Low levels of EPO are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Common causes of cellular hypoxia resulting in elevated levels of EPO include any anemia, and hypoxemia due to chronic lung disease.

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.

<span class="mw-page-title-main">Amgen</span> American multinational biopharmaceutical company

Amgen Inc. is an American multinational biopharmaceutical company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen's Thousand Oaks staff in 2022 numbered approximately 5,000 and included hundreds of scientists, making Amgen the largest employer in Ventura County. As of 2022, Amgen has approximately 24,000 staff in total.

Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

Cytopenia is a reduction in the number of mature blood cells. It can have many causes, and commonly occurs in people with cancer being treated with radiation therapy or chemotherapy.

Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin production and release from the liver. Hepcidin production and release shuts down ferroportin, a protein that controls export of iron from the gut and from iron storing cells. As a consequence, circulating iron levels are reduced. Other mechanisms may also play a role, such as reduced erythropoiesis. It is also known as anemia of inflammation, or anemia of inflammatory response.

<span class="mw-page-title-main">Joseph W. Eschbach</span>

Joseph Wetherill Eschbach was an American doctor and kidney specialist whose twenty years of research starting in the 1960s led to an improvement in the treatment of anemia.

<span class="mw-page-title-main">Erythropoiesis-stimulating agent</span> Medicine that stimulates red blood cell production

Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In these situations they decrease the need for blood transfusions. The different agents are more or less equivalent. They are given by injection.

Epoetin beta (INN), sold under the brand name Neorecormon among others, is a synthetic, recombinant form of erythropoietin, a protein that promotes the production of red blood cells. It is an erythropoiesis-stimulating agent (ESA) that is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy.

Methoxy polyethylene glycol-epoetin beta, sold under the brand name Mircera, is a long-acting erythropoietin receptor activator (CERA) used for the treatment of anaemia associated with chronic kidney disease. It is the first approved, chemically modified erythropoiesis-stimulating agent (ESA).

<span class="mw-page-title-main">Robert Provenzano</span> American physician

Robert Provenzano is an American nephrologist. He is also an Associate Clinical Professor of Medicine at Wayne State University School of Medicine.

Continuous erythropoietin receptor activator (CERA) is the generic term for drugs in a new class of third-generation erythropoiesis-stimulating agents (ESAs). In the media, these agents are commonly referred to as 'EPO', short for erythropoietin. CERAs have an extended half-life and a mechanism of action that promotes increased stimulation of erythropoietin receptors compared with other ESAs.

Eugene Goldwasser was an American biochemist at the University of Chicago who identified erythropoietin, a hormone that plays a vital role in the synthesis of red blood cells. After sharing the minute quantities that he had been able to isolate with researchers at the biotechnology firm Amgen, that company was able to use genetic engineering technology to produce useful amounts of erythropoietin as a drug to treat anemia that has achieved substantial financial success, but that has also been used by athletes as a performance-enhancing drug.

Peginesatide, developed by Affymax and Takeda, is an erythropoietic agent, a functional analog of erythropoietin.

CSL Vifor is a global specialty pharmaceuticals company in the treatment areas of iron deficiency, dialysis, nephrology & rare disease. It is headquartered in Switzerland and consists of CSL Vifor, Vifor Fresenius Medical Care Renal Pharma (VFMCRP) and Sanifit Therapeutics.

<span class="mw-page-title-main">Roxadustat</span> Anti-anemia medication

Roxadustat, sold under the brand name Evrenzo, is an anti-anemia medication. Roxadustat is a HIF prolyl-hydroxylase inhibitor that increases endogenous production of erythropoietin and stimulates production of hemoglobin and red blood cells. It was investigated in clinical trials for the treatment of anemia caused by chronic kidney disease (CKD). It is taken by mouth. The drug was developed by FibroGen, in partnership with AstraZeneca.

<span class="mw-page-title-main">Daprodustat</span> Chemical compound

Daprodustat, sold under the brand name Duvroq among others, is a medication that is used for the treatment of anemia due to chronic kidney disease. It is a hypoxia-inducible factor prolyl hydroxylase inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Desidustat</span> Chemical compound

Desidustat is a drug for the treatment of anemia of chronic kidney disease. This drug with the brand name Oxemia is discovered and developed by Zydus Life Sciences. Desidustat reduces the requirement of recombinant erythropoietin requirement in anemia, and decreases EPO-resistance, by reducing IL-6, IL-1β, and anti-EPO antibodies. The subject expert committee of CDSCO has recommended the grant of permission for manufacturing and marketing of Desidustat 25 mg and 50 mg tablets in India,based on some conditions related to package insert, phase 4 protocols, prescription details, and GCP. Clinical trials on desidustat have been done in India and Australia. In a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study, a mean hemoglobin increase of 1.57, 2.22, and 2.92 g/dL in desidustat 100, 150, and 200 mg arms, respectively, was observed. The Phase 3 clinical trials were conducted in chronic kidney disease patients which were not on dialysis as well as on dialysis. Desidustat is developed for the treatment of anemia as an oral tablet, where currently injections of erythropoietin and its analogues are drugs of choice. Desidustat is a HIF prolyl-hydroxylase inhibitor. In preclinical studies, effects of desidustat was assessed in normal and nephrectomized rats, and in chemotherapy-induced anemia. Desidustat demonstrated hematinic potential by combined effects on endogenous erythropoietin release and efficient iron utilization. Desidustat can also be useful in treatment of anemia of inflammation since it causes efficient erythropoiesis and hepcidin downregulation. In January 2020, Zydus entered into licensing agreement with China Medical System (CMS) Holdings for development and commercialization of desidustat in Greater China. Under the license agreement, CMS will pay Zydus an initial upfront payment, regulatory milestones, sales milestones and royalties on net sales of the product. CMS will be responsible for development, registration and commercialization of desidustat in Greater China. It has been observed that desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines like IL-6 and oxidative stress. A clinical trial to evaluate the efficacy and safety of desidustat tablet for the management of COVID-19 patients is ongoing in Mexico, wherein desidustat has shown to prevent acute respiratory distress syndrome (ARDS) by inhibiting IL-6. Zydus has also received approval from the US FDA to initiate clinical trials of desidustat in chemotherapy Induced anemia (CIA).

References

  1. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  2. ↑ "Epogen- epoetin alfa solution". DailyMed. 25 July 2018.
  3. ↑ "Retacrit- epoetin alfa-epbx injection, solution". DailyMed. 29 January 2020.
  4. 1 2 "Abseamed EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 2 April 2020.
  5. ↑ "Abseamed". Union Register of medicinal products. Retrieved 14 January 2021.
  6. ↑ Walsh G, Spada S (2005). "Epogen/Procrit". Directory of approved biopharmaceutical products. Boca Raton: CRC Press. pp.  39–41. ISBN   978-0-415-26368-9.
  7. ↑ Engelberg AB, Kesselheim AS, Avorn J (November 2009). "Balancing innovation, access, and profits--market exclusivity for biologics". The New England Journal of Medicine. 361 (20): 1917–9. doi:10.1056/NEJMp0908496. PMID   19828525.
  8. ↑ Elliott S, Lorenzini T, Asher S, Aoki K, Brankow D, Buck L, et al. (April 2003). "Enhancement of therapeutic protein in vivo activities through glycoengineering". Nature Biotechnology. 21 (4): 414–21. doi:10.1038/nbt799. PMID   12612588. S2CID   7214868.
  9. ↑ "Testimony Before the Subcommittee on Health, Committee on Energy and Commerce, House of Representatives.] Medicare. Information on Highest-Expenditure Part B Drugs." (PDF), United States Government Accountability Office (GAO), 28 June 2013, retrieved 29 June 2015
  10. ↑ Mitka M (14 August 2013), "Capitol Health Call: High-Cost Drugs Account for Most of Medicare Part B Spending", JAMA, 310 (6): 572, doi:10.1001/jama.2013.192555
  11. ↑ Anemia drugs made billions, but at what cost? By Peter Whoriskey, The Washington Post, 19 July 2012
  12. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  13. ↑ Macdougall IC, Tucker B, Thompson J, Tomson CR, Baker LR, Raine AE (November 1996). "A randomized controlled study of iron supplementation in patients treated with erythropoietin". Kidney International. 50 (5): 1694–9. doi: 10.1038/ki.1996.487 . PMID   8914038.
  14. ↑ Fitzsimons, Helen (14 November 2020). "ERYTHROPOIESIS STIMULATING AGENTS (ESAs) FOR SEVERE ANAEMIA". Tanya's Feline CKD Website. Retrieved 17 September 2023.
  15. ↑ Ruben, Dr. Dawn (6 August 2015). "Erythropoietin (Epogen®, Procrit®) for Dogs and Cats". PetPlace. Retrieved 17 September 2023.
  16. ↑ Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S, An R, Bowers PJ, Burton P, Klausner MA, Corwin MJ (September 2007). "Efficacy and safety of epoetin alfa in critically ill patients". The New England Journal of Medicine. 357 (10): 965–76. doi: 10.1056/NEJMoa071533 . PMID   17804841.
  17. ↑ Ehrenreich H, Degner D, Meller J, Brines M, Béhé M, Hasselblatt M, Woldt H, Falkai P, Knerlich F, Jacob S, von Ahsen N, Maier W, Brück W, Rüther E, Cerami A, Becker W, Sirén AL (January 2004). "Erythropoietin: a candidate compound for neuroprotection in schizophrenia". Molecular Psychiatry. 9 (1): 42–54. doi: 10.1038/sj.mp.4001442 . PMID   14581931. S2CID   22595839.
  18. ↑ Casals-Pascual C, Idro R, Picot S, Roberts DJ, Newton CR (January 2009). "Can erythropoietin be used to prevent brain damage in cerebral malaria?". Trends in Parasitology. 25 (1): 30–6. doi:10.1016/j.pt.2008.10.002. PMID   19008152.
  19. ↑ Core A, Hempel C, Kurtzhals JA, Penkowa M (February 2011). "Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model". Experimental Parasitology. 127 (2): 500–5. doi:10.1016/j.exppara.2010.09.010. PMID   21044627.
  20. ↑ McKie R (17 February 2008). "Kidney drug could save children from malaria brain damage". The Guardian. London.
  21. ↑ Banks WA, Jumbe NL, Farrell CL, Niehoff ML, Heatherington AC (November 2004). "Passage of erythropoietic agents across the blood-brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa". European Journal of Pharmacology. 505 (1–3): 93–101. doi:10.1016/j.ejphar.2004.10.035. PMID   15556141.
  22. ↑ Ott CV, Vinberg M, Kessing LV, Miskowiak KW (August 2016). "The effect of erythropoietin on cognition in affective disorders - Associations with baseline deficits and change in subjective cognitive complaints". European Neuropsychopharmacology. 26 (8): 1264–1273. doi:10.1016/j.euroneuro.2016.05.009. PMID   27349944. S2CID   2335208.
  23. 1 2 Ohlsson A, Aher SM (February 2020). "Early erythropoiesis-stimulating agents in preterm or low birth weight infants". The Cochrane Database of Systematic Reviews. 2 (2): CD004863. doi:10.1002/14651858.CD004863.pub6. PMC   7014351 . PMID   32048730.
  24. 1 2 Aher SM, Ohlsson A (February 2020). "Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants". The Cochrane Database of Systematic Reviews. 2 (2): CD004865. doi:10.1002/14651858.CD004865.pub4. PMC   7014632 . PMID   32048729.
  25. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 547-549.
  26. ↑ Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A (November 2006). "Normalization of hemoglobin level in patients with chronic kidney disease and anemia". The New England Journal of Medicine. 355 (20): 2071–84. doi: 10.1056/NEJMoa062276 . PMID   17108342.
  27. ↑ "FDA Public Health Advisory: Erythropoiesis-Stimulating Agents (ESAs): Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp)". Food and Drug Administration . Archived from the original on 28 May 2007. Retrieved 5 June 2007.
  28. ↑ "Information for Healthcare Professionals: Erythropoiesis Stimulating Agents (ESA)". Food and Drug Administration . Archived from the original on 15 May 2007. Retrieved 5 June 2007.
  29. ↑ "Erythropoiesis Stimulating Agents: Aranesp (darbepoetin alfa), Epogen (epoetin alfa), and Procrit (epoetin alfa)". MedWatch - 2007 Safety Information Alerts. U.S. Food and Drug Administration. 3 January 2008. Archived from the original on 9 April 2009. Retrieved 9 April 2009.
  30. ↑ "Procrit (Epoetin alfa) for injection" (PDF). U.S. Food and Drug Administration. 11 August 2007. Archived from the original (PDF) on 18 January 2009. Retrieved 9 April 2009.
  31. ↑ "Aranesp (darbepoetin alfa) for Injection" (PDF). U.S. Food and Drug Administration. 8 November 2007. Archived from the original (PDF) on 18 January 2009. Retrieved 9 April 2009.
  32. ↑ "Information on Erythropoiesis Stimulating Agents (ESA) (marketed as Procrit, Epogen, and Aranesp)". U.S. Food and Drug Administration. 26 January 2009. Retrieved 9 April 2009.
  33. ↑ "Epoetin alfa Interactions Checker". Drugs.com.
  34. ↑ Hardell L, Walker MJ, Walhjalt B, Friedman LS, Richter ED (March 2007). "Secret ties to industry and conflicting interests in cancer research". American Journal of Industrial Medicine. 50 (3): 227–33. doi: 10.1002/ajim.20357 . PMID   17086516.
  35. ↑ Maryann Napoli (5 October 2011), Whistleblower's story: New book reviewed, Center for Medical Consumers, archived from the original on 5 January 2012, retrieved 12 February 2012{{citation}}: CS1 maint: bot: original URL status unknown (link)| archive-url= | archive-date=5 January 2012
  36. ↑ Edwards J (17 August 2009). "Drug Rep in $3B Procrit Case: "80% of My Sales Were Medicare Fraud"; Carried $400K in "Cash"". CBS news. Retrieved 12 February 2012.
  37. ↑ "Binocrit EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 2 April 2020.
  38. ↑ "Epoetin Alfa Hexal EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 2 April 2020.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.