Revision as of 19:41, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,084 edits Saving copy of the {{drugbox}} taken from revid 472863863 of page Abatacept for the Chem/Drugbox validation project (updated: 'ChEMBL', 'KEGG', 'CAS_number'). |
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{{Short description|Immunomodulating pharmaceutical drug}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{cs1 config|name-list-style=vanc}} |
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{{Use dmy dates|date=March 2022}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 456662913 |
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| verifiedrevid = 477237032 |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = Orencia |
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| tradename = Orencia |
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| Drugs.com = {{drugs.com|monograph|abatacept}} |
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| Drugs.com = {{drugs.com|monograph|abatacept}} |
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| MedlinePlus = a606016 |
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| MedlinePlus = a606016 |
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| licence_EU = yes |
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| pregnancy_category = C <small>(])</small> |
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| DailyMedID = Abatacept |
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| legal_status = POM <small>(])</small>, ℞-only <small>(U.S.)</small> |
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| pregnancy_AU = C |
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| routes_of_administration = ] |
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| routes_of_administration = ], ] |
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| ATC_prefix = L04 |
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| ATC_suffix = AA24 |
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| legal_UK = POM |
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<!--Pharmacokinetic data--> |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Orencia FDA label">{{cite web | title=Orencia- abatacept injection, powder, lyophilized, for solution Orencia- abatacept injection, solution | website=DailyMed | date=15 December 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0836c6ac-ee37-5640-2fed-a3185a0b16eb | access-date=16 March 2022}}</ref><ref>{{cite web | title=FDA approves abatacept for prophylaxis of acute graft | website=U.S. ] (FDA) | date=15 December 2021 | url=http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-abatacept-prophylaxis-acute-graft-versus-host-disease | archive-url=https://web.archive.org/web/20220124140010/http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-abatacept-prophylaxis-acute-graft-versus-host-disease | archive-date=24 January 2022 | url-status=live | access-date=16 March 2022}}</ref> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Orencia EPAR">{{cite web | title=Orencia EPAR | website=] (EMA) | date=5 June 2007 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/orencia | access-date=6 October 2020}}</ref> |
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| legal_status = |
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<!-- Pharmacokinetic data --> |
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| elimination_half-life = 13.1 days |
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| elimination_half-life = 13.1 days |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| CAS_number = 332348-12-6 |
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| ChemSpiderID = NA |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| DrugBank = DB01281 |
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| CAS_number = <!-- blanked - oldvalue: 213252-14-3 --> |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ATC_prefix = L04 |
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| ChemSpiderID = none |
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| ATC_suffix = AA24 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 7D0YB67S97 |
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| DrugBank = DB01281 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D03203 |
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| UNII = 7D0YB67S97 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1201823 |
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| KEGG = <!-- blanked - oldvalue: D03203 --> |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 1201823 --> |
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<!-- Chemical data --> |
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| C = 3498 |
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| H = 5458 |
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| N = 922 |
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| O = 1090 |
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| S = 32 |
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}} |
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}} |
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'''Abatacept''', sold under the brand name '''Orencia''', is a medication used to treat autoimmune diseases like ], by interfering with the immune activity of ]s.<ref name="Orencia FDA label" /><ref name="Orencia EPAR" /> It is a modified antibody.<ref name="Orencia FDA label" /><ref name="Orencia EPAR" /> |
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Abatacept is a ] composed of the Fc region of the ] IgG1 fused to the extracellular domain of ]. In order for a ] to be activated and produce an immune response, an ] must present two signals to the T cell. One of those signals is the ] (MHC), combined with the antigen, and the other signal is the ] or ] molecule (also known as B7-1 and B7-2). Abatacept binds to the CD80 and CD86 molecule, and prevents the second signal. Without the second signal, the T cell can't be activated. |
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Abatacept was developed by ] and is licensed in the United States for the treatment of rheumatoid arthritis in the case of inadequate response to anti-] therapy. Abatacept received approval from the FDA in 2005.<ref>{{cite web|title=Drug Approval Package: Orencia (Abatacept) NDA #125118|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/125118_s0000_OrenciaTOC.cfm |access-date=29 December 2020|website=U.S. ] (FDA) }}</ref> |
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==Medical uses== |
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Abatacept is used to treat adults with moderate to severe ] (RA) as a second-line agent, and as a first-line agent for people whose RA is severe and rapidly progressing. It also used to treat ] and ].<ref name="Orencia FDA label" /><ref name=UKlabelPen>{{cite web|title=UK label prefilled pen|url=https://www.medicines.org.uk/emc/medicine/30346|publisher=UK Electronic Medicines Compendium|date=25 July 2017}}</ref><ref name=UKlabelPowder>{{cite web|title=UK label powder|url=https://www.medicines.org.uk/emc/medicine/19714|publisher=UK Electronic Medicines Compendium|date=25 July 2017}}</ref><ref name="Orencia EPAR" /> |
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==Contraindications== |
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Abatacept has not been tested in pregnant women and it is not known if it is secreted in breast milk; it causes birth defects in rodents when given in very high doses, and is transmitted in rodent breast milk.<ref name=UKlabelPen/> |
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Abatacept will likely interfere with any vaccine given while people are taking it.<ref name=UKlabelPen/> |
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It should not be used in combination with ] or ]s.<ref name=Moreland>{{cite journal | vauthors= Moreland L, Bate G, Kirkpatrick P | title=Abatacept | journal= Nature Reviews Drug Discovery | year= 2006 | volume= 5 | pages= 185–186 | pmid= 16557658 | doi=10.1038/nrd1989 | issue= 3| s2cid=266176720 }}</ref> Because abatacept, anakinra, and TNF antagonists suppress the immune system, using them in combination may significantly increase the risk for severe infections.<ref name="Orencia FDA label"/> |
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==Adverse effects== |
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People have experienced serious infections due to abatacept's suppression of the immune system; some of these infections have been fatal. People with ] are likely to get lung infections more often than usual. Some people have had ] reactions to the drug. Abatacept may cause otherwise slow-growing ] to proliferate and ], due to suppression of the immune system.<ref name=UKlabelPen/> |
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Very common adverse effects (occurring in more than 10% of people) include upper respiratory tract infections. Common adverse effects (occurring in between 1% and 10% of people) include lower respiratory tract infections, urinary tract infections, herpes infections, pneumonia, flu, cough, high blood pressure, stomach pain, diarrhea, nausea, vomiting, upset stomach, mouth sores, ], rashes, fatigue, weakness, local injection site reactions, and systemic injection reactions.<ref name=UKlabelPen/> |
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==Chemistry== |
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Abatacept is a ] composed of the extracellular domain of ] with the hinge, CH2, and CH3 domains of ].<ref name="Moreland" /> |
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==Mechanism of action== |
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Abatacept is a soluble CTLA-4 analog that prevents ] (APCs) from delivering the co-stimulatory signal. This prevents the T cells from being ], and even downregulates them. Simple signaling without co-stimulation allows the cell to recognize the primary signal as "self" and not ramp-up responses for future responses as well. |
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In order for T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an APC. |
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That activation requires two signals (one of which is called co-stimulatory signal or signal 2): |
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For signal 1, the APC must bind the antigen to a ] (MHC) molecule, bring that complex to its surface, and present it to the T cell receptor on the surface of the T cell. |
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For signal 2, the APC must present a B7 protein (] or ]) on its cell surface to a ] protein on the surface of the T cell. These two signals activate the T cell. Without signal 2, the T cell will not be activated, and will become ]. |
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Abatacept, which consists of a fusion protein of the extracellular domain of CTLA-4 and human IgG1, binds to the B7 protein on the APC and prevents it from delivering the co-stimulatory signal to the T cell.<ref>{{cite web | url = http://www.healthvalue.net/ctlaigenglish.html | title = ABATACEPT & BELATACEPT: the CTLA-4-Igs | publisher = Healthvalue.net | access-date = 25 May 2007 | archive-date = 5 December 2008 | archive-url = https://web.archive.org/web/20081205034856/http://www.healthvalue.net/ctlaigenglish.html | url-status = dead }}</ref><ref>{{cite journal | vauthors= Dall'Era M, Davis J| title=CTLA4Ig: a novel inhibitor of co-stimulation | journal= Lupus | year= 2004 | volume= 13 | issue=5 | pages= 372–376 | pmid= 15230295| doi=10.1191/0961203303lu1029oa| s2cid=32235606 }}</ref> |
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==References== |
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{{Reflist}} |
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== External links == |
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* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/abatacept | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Abatacept }} |
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{{Immunosuppressants}} |
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{{Portal bar | Medicine}} |
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