Deferasirox, sold under the brand name Exjade & Asunra (in injectable form) & Oleptiss (Tablet formulation) both by Novartis among others, is an oral ironchelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias.[3][4] It is the first oral medication approved in the United States for this purpose.[5]
The half-life of deferasirox is between 8 and 16 hours allowing once a day dosing. Two molecules of deferasirox are capable of binding to 1 atom of iron which are subsequently eliminated by fecal excretion. Its low molecular weight and high lipophilicity allows the drug to be taken orally unlike deferoxamine which has to be administered by IV route (intravenous infusion). Together with deferiprone, deferasirox seems to be capable of removing iron from cells (cardiac myocytes and hepatocytes) as well as removing iron from the blood.
Synthesisedit
Deferasirox can be prepared from simple commercially available starting materials (salicylic acid, salicylamide and 4-hydrazinobenzoic acid) in the following two-step synthetic sequence:
Image to be added
The condensation of salicyloyl chloride (formed in situ from salicylic acid and thionyl chloride) with salicylamide under dehydrating reaction conditions results in formation of 2-(2-hydroxyphenyl)-1,3(4H)-benzoxazin-4-one. This intermediate is isolated and reacted with 4-hydrazinobenzoic acid in the presence of base to give 4-(3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl)benzoic acid (deferasirox).[12]
Risksedit
Deferasirox ranked second on the list of drugs most frequently suspected in reported patient deaths compiled for 2019 by the Institute for Safe Medical Practices, with 1320 suspected deaths.[13] A boxed warning was added in the same year with regard to kidney failure, liver failure and gastrointestinal bleeding.[14] It is suspected that the main driver of this spike in suspected deaths relates to the re-analysis of adverse event data by Novartis.[13]
Referencesedit
^"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 Oct 2023.
^"Material Safety Data Sheet (MSDS): Deferasirox". ChemSrc. 2018.
^ abChoudhry VP, Naithani R (August 2007). "Current status of iron overload and chelation with deferasirox". Indian Journal of Pediatrics. 74 (8): 759–64. doi:10.1007/s12098-007-0134-7. PMID 17785900. S2CID 19930076. Free full text 2014-04-29 at the Wayback Machine
^Yang LP, Keam SJ, Keating GM (2007). "Deferasirox : a review of its use in the management of transfusional chronic iron overload". Drugs. 67 (15): 2211–30. doi:10.2165/00003495-200767150-00007. PMID 17927285. S2CID 195686285.
^ ab"FDA Approves First Oral Drug for Chronic Iron Overload" (Press release). United States Food and Drug Administration. November 9, 2005. Retrieved 2007-10-31.
^(PDF). European Medicines Agency. 2018. Archived from the original (PDF) on 2017-12-29. Retrieved 2012-11-26.
^Kontoghiorghes GJ (April 2013). "Turning a blind eye to deferasirox's toxicity?". Lancet. 381 (9873): 1183–4. doi:10.1016/S0140-6736(13)60799-0. PMID 23561999. S2CID 27794849.
^. Archived from the original on 2016-03-04. Retrieved 2013-04-20.
^World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^"Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration. Retrieved 15 August 2020.
^Steinhauser S, Heinz U, Bartholomä M, Weyhermüller T, Nick H, Hegetschweiler K (2004). "Complex Formation of ICL670 and Related Ligands with FeIII and FeII". European Journal of Inorganic Chemistry. 2004 (21): 4177–4192. doi:10.1002/ejic.200400363.]
^ ab"QuarterWatch™ (Quarter 4 and 2009 totals): Reported Patient Deaths Increased by 14% in 2009". Institute For Safe Medication Practices. Retrieved 2021-06-28.
^Pediatrics AA (2010-02-19). . AAP News. doi:10.1542/aapnews.20100219-1 (inactive 31 January 2024). ISSN 1073-0397. Archived from the original on 2021-06-28. Retrieved 2021-06-28.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
deferasirox, sold, under, brand, name, exjade, asunra, injectable, form, oleptiss, tablet, formulation, both, novartis, among, others, oral, iron, chelator, main, reduce, chronic, iron, overload, patients, receiving, long, term, blood, transfusions, conditions. Deferasirox sold under the brand name Exjade amp Asunra in injectable form amp Oleptiss Tablet formulation both by Novartis among others is an oral iron chelator Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta thalassemia and other chronic anemias 3 4 It is the first oral medication approved in the United States for this purpose 5 DeferasiroxClinical dataPronunciationde FER a sir oxTrade namesExjade JadenuOther namesCGP 72670 ICL 670A IC L670AHFS Drugs comMonographLicense dataEU EMA by INN US DailyMed DeferasiroxPregnancycategoryAU CRoutes ofadministrationBy mouthATC codeV03AC03 WHO Legal statusLegal statusAU S4 Prescription only UK POM Prescription only US WARNING 1 Rx only EU Rx only In general Prescription only Pharmacokinetic dataBioavailability70 Protein binding99 MetabolismHepatic glucuronidationElimination half life8 to 16 hoursExcretionFecal 84 and renal 8 IdentifiersIUPAC name 4 3 5 Bis 2 hydroxyphenyl 1H 1 2 4 triazol 1 yl benzoic acidCAS Number201530 41 8 YPubChem CID214348DrugBankDB01609 YChemSpider4591431 YUNIIV8G4MOF2V9KEGGD03669 YChEBICHEBI 49005ChEMBLChEMBL550348 YCompTox Dashboard EPA DTXSID1048596ECHA InfoCard100 211 077Chemical and physical dataFormulaC 21H 15N 3O 4Molar mass373 368 g mol 13D model JSmol Interactive imageDensity1 4 0 1 g cm3 2 SMILES OC O c1ccc cc1 n2nc nc2c3ccccc3O c4ccccc4OInChI InChI 1S C21H15N3O4 c25 17 7 3 1 5 15 17 19 22 20 16 6 2 4 8 18 16 26 24 23 19 14 11 9 13 10 12 14 21 27 28 h1 12 25 26H H 27 28 YKey BOFQWVMAQOTZIW UHFFFAOYSA N Y N Y what is this verify It was approved by the U S Food and Drug Administration FDA in November 2005 3 5 According to the FDA May 2007 kidney failure and cytopenias have been reported in patients receiving deferasirox tablets for oral suspension It is approved in the European Union by the European Medicines Agency EMA for children six years and older for chronic iron overload from repeated blood transfusions 6 7 8 It is on the World Health Organization s List of Essential Medicines 9 In July 2020 Teva decided to discontinue deferasirox 10 It is available as a generic medication 11 Contents 1 Properties 2 Synthesis 3 Risks 4 ReferencesProperties edit nbsp Two deferasirox molecules binding iron The half life of deferasirox is between 8 and 16 hours allowing once a day dosing Two molecules of deferasirox are capable of binding to 1 atom of iron which are subsequently eliminated by fecal excretion Its low molecular weight and high lipophilicity allows the drug to be taken orally unlike deferoxamine which has to be administered by IV route intravenous infusion Together with deferiprone deferasirox seems to be capable of removing iron from cells cardiac myocytes and hepatocytes as well as removing iron from the blood Synthesis editDeferasirox can be prepared from simple commercially available starting materials salicylic acid salicylamide and 4 hydrazinobenzoic acid in the following two step synthetic sequence nbsp Image to be added The condensation of salicyloyl chloride formed in situ from salicylic acid and thionyl chloride with salicylamide under dehydrating reaction conditions results in formation of 2 2 hydroxyphenyl 1 3 4H benzoxazin 4 one This intermediate is isolated and reacted with 4 hydrazinobenzoic acid in the presence of base to give 4 3 5 bis 2 hydroxyphenyl 1 2 4 triazol 1 yl benzoic acid deferasirox 12 Risks editDeferasirox ranked second on the list of drugs most frequently suspected in reported patient deaths compiled for 2019 by the Institute for Safe Medical Practices with 1320 suspected deaths 13 A boxed warning was added in the same year with regard to kidney failure liver failure and gastrointestinal bleeding 14 It is suspected that the main driver of this spike in suspected deaths relates to the re analysis of adverse event data by Novartis 13 References edit 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 Oct 2023 Material Safety Data Sheet MSDS Deferasirox ChemSrc 2018 a b Choudhry VP Naithani R August 2007 Current status of iron overload and chelation with deferasirox Indian Journal of Pediatrics 74 8 759 64 doi 10 1007 s12098 007 0134 7 PMID 17785900 S2CID 19930076 Free full text Archived 2014 04 29 at the Wayback Machine Yang LP Keam SJ Keating GM 2007 Deferasirox a review of its use in the management of transfusional chronic iron overload Drugs 67 15 2211 30 doi 10 2165 00003495 200767150 00007 PMID 17927285 S2CID 195686285 a b FDA Approves First Oral Drug for Chronic Iron Overload Press release United States Food and Drug Administration November 9 2005 Retrieved 2007 10 31 Exjade deferasirox PDF European Medicines Agency 2018 Archived from the original PDF on 2017 12 29 Retrieved 2012 11 26 Kontoghiorghes GJ April 2013 Turning a blind eye to deferasirox s toxicity Lancet 381 9873 1183 4 doi 10 1016 S0140 6736 13 60799 0 PMID 23561999 S2CID 27794849 Review Exjade side effects Archived from the original on 2016 03 04 Retrieved 2013 04 20 World Health Organization 2023 The selection and use of essential medicines 2023 web annex A World Health Organization model list of essential medicines 23rd list 2023 Geneva World Health Organization hdl 10665 371090 WHO MHP HPS EML 2023 02 Deferasirox Discontinuation U S Food and Drug Administration FDA Retrieved 20 July 2020 Drugs FDA FDA Approved Drugs U S Food and Drug Administration Retrieved 15 August 2020 Steinhauser S Heinz U Bartholoma M Weyhermuller T Nick H Hegetschweiler K 2004 Complex Formation of ICL670 and Related Ligands with FeIII and FeII European Journal of Inorganic Chemistry 2004 21 4177 4192 doi 10 1002 ejic 200400363 a b QuarterWatch Quarter 4 and 2009 totals Reported Patient Deaths Increased by 14 in 2009 Institute For Safe Medication Practices Retrieved 2021 06 28 Pediatrics AA 2010 02 19 Black box warning added to Exjade AAP News doi 10 1542 aapnews 20100219 1 inactive 31 January 2024 ISSN 1073 0397 Archived from the original on 2021 06 28 Retrieved 2021 06 28 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint DOI inactive as of January 2024 link Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Deferasirox amp oldid 1212536912, wikipedia, wiki, book, books, library,
