Erythropoiesis-stimulating agent
Erythropoiesis-stimulating agent | |
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Erythropoiesis-stimulating agents (ESA) are
Common side effects may include
They were first approved for medical use in the United States in 1989.[5] It is on the World Health Organization's List of Essential Medicines.[7] Commercially available agents include epoetin alfa and darbepoetin alfa, and biosimilars.[1][2] Use among athletes is prohibited by the World Anti-Doping Agency.[5]
Medical uses
ESAs are used to maintain hemoglobin at the lowest level that both minimizes transfusions and best meets a person's needs.
The 2020 Cochrane Anaesthesia Review Group review of erythropoietin (EPO) plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non‐cardiac surgery[11] demonstrated that patients were much less likely to require red cell transfusion and in those transfused, the volumes were unchanged (mean difference -0.09, 95% CI -0.23 to 0.05). Pre-op hemoglobin (Hb) concentration was increased in those receiving 'high dose' EPO, but not 'low dose'.[citation needed]
There is no evidence that one agent is better than another in the setting of CKD.[12]
Failure
ESAs may fail to achieve an adequate therapeutic response when one or more of the following is present:[13]
- Occult blood loss and/or iron deficiency
- Vitamin B12 or folate deficiency
- Infection and inflammation
- Inadequate dialysis
- Hyperparathyroidism
- Aluminum toxicity
- Patient adherence
- Hypothyroidism
- Primary disease activity
- Transplant rejection
- Malignancy
- Pure red cell aplasia
Types
The following types of ESAs are available:[citation needed]
- Erythropoietin (Epo)
- Epoetin alfa (Procrit, Epogen)
- Epoetin beta (NeoRecormon)
- Epoetin zeta (Silapo, Retacrit)
- Darbepoetin alfa (Aranesp)
- Methoxy polyethylene glycol-epoetin beta (Mircera)
Available forms
Recombinant erythropoietin has a variety of glycosylation patterns giving rise to alpha, beta, delta, and omega forms:
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Darbepoetin alfa, which early literature during its development often termed as novel erythropoiesis-stimulating protein (NESP), is a form created by five substitutions (Asn-30, Thr-32, Val-87, Asn-88 and Thr-90) that create two new N-glycosylation sites.[24] This glycoprotein has a longer terminal half-life, meaning it is possible to administer it less frequently.
Misuse
Erythropoiesis-stimulating agents have a history of use as
Though EPO was believed to be widely used in the 1990s in certain sports, there was no way at the time to directly test for it, until in 2000, when a test developed by scientists at the French national antidoping laboratory (LNDD) and endorsed by the World Anti-Doping Agency (WADA) was introduced to detect pharmaceutical EPO by distinguishing it from the nearly identical natural hormone normally present in an athlete's urine. The first EPO-doping cases were found by the Swiss Laboratory for Doping Analyses.[27]
In 2002, at the
Since 2002, EPO tests performed by US sports authorities have consisted of only a urine or "direct" test. From 2000 to 2006, EPO tests at the Olympics were conducted on both blood and urine.
Inhalation of a xenon/oxygen mixture activates production of the transcription factor HIF-1-alpha, which leads to increased production of erythropoietin and improved performance. It has been used for this purpose in Russia since at least 2004.[33]
Cycling
Recombinant EPO is believed to have come into use in cycling about 1990.
Dr. Michele Ferrari, a former student and protege of Conconi,[37] had a controversial interview mentioning the drug in 1994, just after his Gewiss–Ballan team had a remarkable performance in the La Flèche Wallonne race. Ferrari told l'Equipe journalist Jean-Michel Rouet that EPO had no "fundamental" effect on performance and that if his riders used it, it would not "scandalize" himself. After the journalist pointed out several riders were suspected of dying from EPO, Ferrari said EPO was not dangerous, and only abuse of it was dangerous, saying, "It's also dangerous to drink 10 liters of orange juice." The 'orange juice' comment has been widely misquoted.[38][39] Ferrari was fired shortly after, but continued to work in the industry with top riders, allegedly including Lance Armstrong.[37][40] That same year, Sandro Donati, working for the Italian National Olympic Committee, presented a report accusing Conconi of being linked to the use of EPO in the sport.[36]
In 1997, the
In the
Witnesses testified that code words used for EPO included "Edgar", "Poe",[49] "Edgar Allan Poe", and "Zumo" (Spanish for 'juice').[50]
Dynepo
Dynepo is the brand name for a form of EPO developed by
Dynepo was made in cultured human cells. It was therefore expected to have an authentic human form of sialic acid and other oligosaccharide residues. It was hoped that this would make a longer-acting product than existing brands. There were concerns that such production would also make Dynepo undetectable in the urine tests for EPO used, at that time, to detect doping by athletes. Dynepo was withdrawn from European markets on 17 February 2009, for commercial reasons.[51][21] On July 1, 2009, professional cycling team Silence–Lotto announced that Thomas Dekker was tested positive for Dynepo on a test taken on December 24, 2007, while Dekker was riding for Rabobank.[52]
References
- ^ a b c d e "Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp)". US Food and Drug Administration – Drug Safety Information. 31 March 2017. Archived from the original on 14 April 2022.
- ^ a b c d e f g h Banzi R, Gerardi C (23 December 2016). WHO EML 2016-2017 - Application for erythropoietin-stimulating agents (erythropoietin type blood factors) (PDF) (Report). WHO. WHO EML 2016–2017, Version 3. Archived from the original (PDF) on 31 August 2020.
- S2CID 72017313.
- ^ "Highlights of Prescribing Information" (PDF). FDA. Retrieved 13 December 2017.
- ^ a b c "Epoetin alfa Use During Pregnancy | Drugs.com". Drugs.com. Retrieved 13 December 2017.
- ISBN 9780857111562.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ PMID 18458123.
- ABIM Foundation, American Society of Nephrology, archived from the original(PDF) on April 16, 2012, retrieved August 17, 2012
- PMID 31990982.
- PMID 32790892.
- PMID 36791280.
- ^ Burtis, C.A.; Ashwood, E.R. and Bruns, D.E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th Edition. Elsevier. pp 1554
- ^ "Aranesp(darbepoetin alfa)". Amgen.com. Retrieved 2009-04-29.
- ^ "Aranesp EPAR". European Medicines Agency (EMA). 13 January 2020. Retrieved 10 March 2020.
- ^ "Binocrit EPAR". European Medicines Agency (EMA). 31 October 2019. Retrieved 10 March 2020.
- ^ "Procrit (Epoetin alfa)". Ortho Biotech Products. Archived from the original on 2009-10-26. Retrieved 2009-04-29.
- ^ "Probiomed". probiomed.com.mx. Archived from the original on 2018-03-26. Retrieved 2018-03-21.
- ^ "Abseamed EPAR". European Medicines Agency (EMA). 8 October 2019. Retrieved 10 March 2020.
- ^ "Mircera EPAR". European Medicines Agency (EMA). 20 December 2019. Retrieved 10 March 2020.
- ^ a b "Dynepo EPAR". European Medicines Agency (EMA). 23 April 2009. Retrieved 10 March 2020.
- ^ "Silapo EPAR". European Medicines Agency (EMA). 10 March 2020. Retrieved 10 March 2020.
- ^ "Retacrit EPAR". European Medicines Agency (EMA). 14 January 2020. Retrieved 10 March 2020.
- PMID 10928340.
- ^ "Boxing Scandals". Bleacher Report. December 2011. Retrieved 2011-12-22.
- S2CID 2685044.
- ^ History of the Swiss Laboratory for Doping Analyses Archived 2016-03-29 at the Wayback Machine, www.doping.chuv.ch (page visited on 11 June 2014).
- ^ Steeg JL (2007-02-28). "Catlin has made a career out of busting juicers – USATODAY.com". USA Today. Retrieved 2009-03-31.
- ^ "FDA Reports New Risks Posed by Anemia Drugs" Associated Press story in The Washington Post (August 8, 2012)
- PMID 12470670.
- S2CID 11677786.
- doi:10.13055/ojhmt_3_1_6.121211 (inactive 31 January 2024).)
{{cite journal}}
: CS1 maint: DOI inactive as of January 2024 (link - ^ "Breathe it in". The Economist. 8 February 2014.
- ^ S2CID 34350476.
- PMID 18535134.
- ^ a b Harrison C (2003-03-01). "The Man Who Knows Too Much". Sport Monthly. chrisharrisonwriting. Archived from the original on 2014-02-26.
- ^ a b Gifford B (Jan–Feb 2006). "Paging Doctor Ferrari". Bicycling: 50–59.
- ^ Maloney T (2003). "An Interview With Dr. Michele Ferrari, part two: That l'Equipe Interview". by Jean-Michel Rouet, from l'Equipe, 1994, reprinted excerpt. Cycling News.
- ^ 10 liters of orange juice: see the article on Water intoxication, for example.
- ^ Juliet Macur: Cycle of Lies: The Fall of Lance Armstrong
- ^ Martin DT, Ashenden M, Parisotto R, Pyne D, Hahn AG (March–April 1997). "Blood testing for professional cyclists: What's a fair hematocrit limit?". Sports Science.
- ^ "Pantani: Future 'in doubt'". BBC. 5 June 1999. Retrieved 30 June 2011.
- ^ Millar R (2003-10-23). "The Bare Minimum". Cycling News.
- ^ Startt J (2012-10-15). "Christophe Bassons Interview: 'People Now See I Wasn't Lying'". This Just In. Bicycling.com. Archived from the original on 2012-10-18.
- ^ "Stuart O'Grady admits to doping at 1998 Tour de France". Theaustralian.com.au. 2013-07-25. Retrieved 2013-07-25.
- ^ "Landis admits to illegal drug use". BBC News. 2010-05-20.
- ^ United States Anti Doping Agency. "Report on proceedings under the world anti-doping code and the usada protocol united states anti-doping agency, claimant, v. lance armstrong, respondent. reasoned decision of the united states anti-doping agency" (PDF). USADA. Retrieved 2012-10-28.
- ^ "A lifetime ban: Does the time fit the crime?" Velo News, 12/16/13
- ^ "U.S. Postal Service Pro Cycling Team Investigation". Statement From USADA CEO Travis T. Tygart Regarding The U.S. Postal Service Pro Cycling Team Doping Conspiracy. USADA. 2012-10-10.[permanent dead link]
- ^ Chapman M (2012-10-15). "Cycling's Dirty Truth". Sport, Peddlers. BBC Radio 5. Archived from the original on October 16, 2012.
- ^ Wathion N. "Public statement on Dynepo (epoetin delta)" (PDF). European Medicines Agency. Archived from the original (PDF) on 24 September 2015. Retrieved 31 August 2015.
- ISBN 978-1-4081-3333-0.
External links
- Media related to Erythropoiesis-stimulating agents at Wikimedia Commons
- "Erythropoietin". Drug Information Portal. U.S. National Library of Medicine.
- "Epoetin alfa". Drug Information Portal. U.S. National Library of Medicine.
- "Epoetin beta". Drug Information Portal. U.S. National Library of Medicine.
- "Darbepoetin Alfa". Drug Information Portal. U.S. National Library of Medicine.
- "Methoxy polyethylene glycol-epoetin beta". Drug Information Portal. U.S. National Library of Medicine.