Deferoxamine: Difference between revisions

{{short description|Medication that binds iron and aluminium}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| drug_name =

| INN =

| type =<!-- empty -->

| IUPAC_name = ''N'''-{5-[Acetyl(hydroxy)amino]pentyl}-''N''-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-''N''-hydroxysuccinamide

| image = Deferoxamine-2D-skeletal.png

| width =

| alt =

| image2 = Deferoxamine-3D-vdW.png

| width2 =

| alt2 =

| imageL =

| widthL =

| altL =

| imageR =

| widthR =

| altR =

| caption = Skeletal formula and spacefill model of deferoxamine

<!-- Clinical data -->

| pronounce =

| tradename = Desferal

| Drugs.com = {{drugs.com|monograph|deferoxamine-mesylate}}

| MedlinePlus =

| licence_EU = <!-- EMA requires brand name -->

| licence_US = <!-- FDA may use generic name -->

| DailyMedID = <!-- preference to licence_US -->

| pregnancy_AU = <!-- A/B1/B2/B3/C/D/X -->

| pregnancy_AU_comment =

| pregnancy_US = C

| pregnancy_US_comment =

| pregnancy_category=

| dependency_liability =

| addiction_liability =

| routes_of_administration = {{unbulleted list|intramuscular|intravenous|subcutaneous}}

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->

| legal_AU_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled-->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| legal_US_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment =

| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

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| elimination_half-life = 6 hours

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<!-- Identifiers -->

| CAS_number = 70-51-9

| CAS_supplemental = {{cascite|correct|CAS}}

| ATCvet =

| ATC_prefix = V03

| ATC_suffix = AC01

| ATC_supplemental =

| PubChem = 2973

| PubChemSubstance =

| IUPHAR_ligand =

| DrugBank = DB00746

| ChemSpiderID = 2867

| UNII = J06Y7MXW4D

| KEGG = D03670

| ChEBI = 4356

| ChEMBL = 556

| NIAID_ChemDB =

| synonyms = desferrioxamine B, desferoxamine B, DFO-B, DFB ,N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide

<!-- Chemical data -->

| chemical_formula =

| C=25 | H=48 | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I=

| K= | Li= | Mg= | Mn= | N=6 | Na= | O=8 | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge=

| molecular_weight =

| SMILES = CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN

| Jmol =

| StdInChI = 1S/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34)

| StdInChI_comment = {{stdinchicite|correct|chemspider}}

| StdInChIKey = UBQYURCVBFRUQT-UHFFFAOYSA-N

| density =

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}}

<!-- Definition and medical uses -->

'''Deferoxamine''' ('''DFOA'''), also known as '''desferrioxamine''' and sold under the brand name '''Desferal''', is a medication that binds [[iron]] and [[aluminium]].<ref name=AHFS2016/> It is specifically used in [[iron overdose]], [[hemochromatosis]] either due to multiple [[blood transfusion]]s or an underlying [[genetic condition]], and [[aluminium toxicity]] in people on [[Kidney dialysis|dialysis]].<ref name=AHFS2016/><ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | pages=61–62 }}</ref> It is used by [[intramuscular|injection into a muscle]], [[intravenous|vein]], or [[Subcutaneous injection|under the skin]].<ref name=AHFS2016/>

<!-- Side effects and mechanism -->

Common side effects include pain at the site of injection, diarrhea, vomiting, fever, [[hearing loss]], and eye problems.<ref name=AHFS2016/> Severe [[allergic reactions]] including [[anaphylaxis]] and [[low blood pressure]] may occur.<ref name=AHFS2016/> It is unclear if use during [[pregnancy]] or [[breastfeeding]] is safe for the baby.<ref name="drugs.com">{{cite web|title=Deferoxamine (Desferal) Use During Pregnancy|url=https://www.drugs.com/pregnancy/deferoxamine.html|website=www.drugs.com|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221002833/https://www.drugs.com/pregnancy/deferoxamine.html|archive-date=21 December 2016}}</ref> Deferoxamine is a [[siderophore]] from the bacteria ''[[Streptomyces pilosus]]''.<ref name="Elsevier Health Sciences">{{cite book| vauthors = Giardina PJ, Rivella S | chapter = Thalassemia Syndromes | veditors = Hoffman R, Benz Jr EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J |title=Hematology: Diagnosis and Treatment|date=2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-4041-3|page=515|edition=6th| chapter-url = https://books.google.com/books?id=M5fD7gZSDYMC&pg=PA515|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220111527/https://books.google.ca/books?id=M5fD7gZSDYMC&pg=PA515|archive-date=2016-12-20}}</ref><ref>{{cite journal | vauthors = Keberle H | title = The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism | journal = Annals of the New York Academy of Sciences | volume = 119 | issue = 2 | pages = 758–768 | date = October 1964 | pmid = 14219455 | doi = 10.1111/j.1749-6632.1965.tb54077.x | s2cid = 37277528 }}</ref>

<!-- History and culture -->

Deferoxamine was approved for medical use in the United States in 1968.<ref name=AHFS2016>{{cite web|title=Deferoxamine Mesylate|url=https://www.drugs.com/monograph/deferoxamine-mesylate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221002616/https://www.drugs.com/monograph/deferoxamine-mesylate.html|archive-date=21 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>

==Medical uses==

Deferoxamine is used to treat acute [[iron poisoning]], especially in small children.<ref>{{cite journal | vauthors = Merlot AM, Kalinowski DS, Richardson DR | title = Novel chelators for cancer treatment: where are we now? | journal = Antioxidants & Redox Signaling | volume = 18 | issue = 8 | pages = 973–1006 | date = March 2013 | pmid = 22424293 | doi = 10.1089/ars.2012.4540 }}</ref> This agent is also frequently used to treat [[hemochromatosis]], a disease of iron accumulation that can be either genetic or acquired. Acquired hemochromatosis is common in patients with certain types of chronic [[anemia]] (e.g. [[thalassemia]] and [[myelodysplastic syndrome]]) who require many [[blood transfusion]]s, which can greatly increase the amount of iron in the body. Treatment with iron-chelating drugs such as deferoxamine reduces mortality in persons with sickle cell disease or β‐thalassemia who are transfusion dependent.<ref>{{cite journal | vauthors = Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM | title = The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review | journal = American Journal of Hematology | volume = 93 | issue = 7 | pages = 943–952 | date = July 2018 | pmid = 29635754 | doi = 10.1002/ajh.25103 | doi-access = free }}</ref>

Administration for chronic conditions is generally accomplished by [[subcutaneous injection]] over a period of 8–12 hours each day. Administration of deferoxamine after acute intoxication may color the urine a pinkish red, a phenomenon termed "''vin rosé'' urine". Apart from iron toxicity, deferoxamine can be used to treat [[aluminium]] toxicity (an excess of aluminium in the body) in selected patients. In US, the drug is not FDA-approved for this use. Deferoxamine is also used to minimize [[doxorubicin]]'s cardiotoxic side effects and in the treatment of patients with [[aceruloplasminemia]].<ref name="acerulo1">{{cite journal | vauthors = Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD | title = Use of desferrioxamine in the treatment of aceruloplasminemia | journal = Annals of Neurology | volume = 41 | issue = 3 | pages = 404–407 | date = March 1997 | pmid = 9066364 | doi = 10.1002/ana.410410318 | s2cid = 22425032 }}</ref> Deferoxamine may be effective for improving neurologic outcomes in persons with [[intracranial hemorrhage]], although the evidence supporting the efficacy and safety for this indication was weak.<ref>{{cite journal | vauthors = Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J | title = Deferoxamine therapy for intracerebral hemorrhage: A systematic review | journal = PLOS ONE | volume = 13 | issue = 3 | pages = e0193615 | date = 2018 | pmid = 29566000 | pmc = 5863956 | doi = 10.1371/journal.pone.0193615 | doi-access = free | bibcode = 2018PLoSO..1393615Z }}</ref>

Some published manuscripts suggesting the use of deferoxamine for patients diagnosed with COVID-19 because of the high level of ferritin among them.<ref name="pmid32607779">{{cite journal | vauthors = Abobaker A | title = Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome? | journal = European Journal of Clinical Pharmacology | volume = 76 | issue = 11 | pages = 1619–1620 | date = November 2020 | pmid = 32607779 | pmc = 7325475 | doi = 10.1007/s00228-020-02942-9 | url = }}</ref><ref>{{cite journal | vauthors = Alkattan A, Alabdulkareem K, Kamel A, Abdelseed H, Almutairi Y, Alsalameen E | title = Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients. | journal = Alexandria Journal of Medicine | date = January 2021 | volume = 57 | issue = 1 | pages = 21–27 | doi = 10.1080/20905068.2020.1870788 | pmc = 8108185 }}</ref>

==Adverse effects==

It is unclear if use during [[pregnancy]] is safe for the baby.<ref name="drugs.com"/>

Chronic use of deferoxamine may increase the risk of [[hearing loss]] in patients with [[thalassemia major]].<ref>{{cite journal | vauthors = Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, Delpisheh A, Veisani Y, Soleymani A, Azami M | title = Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis | journal = Caspian Journal of Internal Medicine | volume = 8 | issue = 4 | pages = 239–249 | date = 2017 | pmid = 29201313 | pmc = 5686301 | doi = 10.22088/cjim.8.4.239 }}</ref>

Chronic use of deferoxamine may cause ocular symptoms, [[growth retardation]], local reactions and allergy.<ref name="Taher">{{cite journal | vauthors = Taher AT, Musallam KM, Cappellini MD | title = β-Thalassemias | journal = The New England Journal of Medicine | volume = 384 | issue = 8 | pages = 727–743 | date = February 2021 | pmid = 33626255 | doi = 10.1056/NEJMra2021838 | s2cid = 232049825 }}</ref>

==Mechanism==

Deferoxamine is produced by removal of the trivalent iron moiety from ferrioxamine B, an iron-bearing [[siderophore|sideramine]] produced by the actinomycetes, ''[[Streptomyces pilosus]]''. Its discovery was a serendipitous result of research conducted by scientists at Ciba in collaboration with scientists at the Swiss Federal Institute of Technology in Zurich and the University Hospital in Freiburg, Germany<ref>{{cite journal | vauthors = Yawalkar SJ | title = Milestones in the research and development of desferrioxamine | journal = Nephrology, Dialysis, Transplantation | volume = 8 | issue = Suppl 1 | pages = 40–42 | date = 1993 | pmid = 8389019 | doi = 10.1093/ndt/8.supp1.40 }}</ref><ref name="Elsevier Health Sciences"/> Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the [[urine]]. By removing excess iron from persons with [[hemochromatosis]], the agent reduces the damage done to various organs and tissues, such as the [[liver]]. Also, it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma).{{Citation needed|reason=A citation is needed for the claim that a recent study has shown DFO to speed nerve regeneration|date=August 2013}} Deferoxamine may modulate expression<ref>{{cite journal | vauthors = Lee HJ, Lee J, Lee SK, Lee SK, Kim EC | title = Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes | journal = BMC Cancer | volume = 7 | pages = 176 | date = September 2007 | pmid = 17850672 | pmc = 2078595 | doi = 10.1186/1471-2407-7-176 | doi-access = free }}</ref> and release of inflammatory mediators by specific cell types.<ref>{{cite journal | vauthors = Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, Yoon KH, Kim EA, Han WC, Choi SC, Hwang JY, Park C, Oh BS, Kim Y, Kimm KC, Park KI, Chung HT, Jun CD | title = Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways | journal = Journal of Immunology | volume = 172 | issue = 11 | pages = 7069–7077 | date = June 2004 | pmid = 15153529 | doi = 10.4049/jimmunol.172.11.7069 | doi-access = free }}</ref>

==Research==

Deferoxamine is being studied as a treatment for spinal cord injury<ref>{{cite web | title = Public summary of opinion on orphan designation: Deferoxamine mesylate for the treatment of traumatic spinal cord injury | date = 3 October 2013 | work = Committee for Orphan Medicinal Products | publisher = European Medicines Agency | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b | archive-url = https://web.archive.org/web/20130717223511/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Forphans%2F2009%2F11%2Fhuman_orphan_000120.jsp&mid=WC0b01ac058001d12b | archive-date=2013-07-17 }}</ref> and intracerebral hemorrhage.<ref name="pmid21102602">{{cite journal | vauthors = Wu H, Wu T, Xu X, Wang J, Wang J | title = Iron toxicity in mice with collagenase-induced intracerebral hemorrhage | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 31 | issue = 5 | pages = 1243–1250 | date = May 2011 | pmid = 21102602 | pmc = 3099628 | doi = 10.1038/jcbfm.2010.209 }}</ref><ref name="pmid32423330">{{cite journal | vauthors = Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J | title = Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 40 | issue = 9 | pages = 1752–1768 | date = September 2020 | pmid = 32423330 | pmc = 7446569 | doi = 10.1177/0271678X20923551 }}</ref> It is also used to induce hypoxia-like environment in mesenchymal stem cells.<ref>{{cite journal | vauthors = Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, Jia M, Zhao Q, Cai H, Han ZC, Yang R, Chen G, Zhao RC | title = Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions | journal = Biochemical and Biophysical Research Communications | volume = 347 | issue = 1 | pages = 12–21 | date = August 2006 | pmid = 16814746 | doi = 10.1016/j.bbrc.2006.05.169 }}</ref><ref>{{cite journal | vauthors = Woo KJ, Lee TJ, Park JW, Kwon TK | title = Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway | journal = Biochemical and Biophysical Research Communications | volume = 343 | issue = 1 | pages = 8–14 | date = April 2006 | pmid = 16527254 | doi = 10.1016/j.bbrc.2006.02.116 }}</ref>

Since the terminal amine group of Deferoxamine does not participate in metal chelation, it has been used to immobilize Deferoxamine to surfaces and substrates for various industrial and biomedical applications.<ref>{{cite journal | vauthors = Touma JG, Kelly C, Coblyn M, Jovanovic GN, Schilke K | title = Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate | journal = Industrial & Engineering Chemistry Research | volume = 62 | issue = 37 | pages = 15109–15119 | date = 2023 | doi = 10.1021/acs.iecr.3c00812}}</ref>

== See also ==

*[[Chelation therapy]]

== References ==

{{reflist|32em}}

{{chelating agents}}

{{portal bar|Medicine}}

[[Category:Siderophores]]

[[Category:Carboxamides]]

[[Category:Chelating agents used as drugs]]

[[Category:Wikipedia medicine articles ready to translate]]