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Revision as of 11:22, 8 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 06:30, 7 April 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,153 edits add CA 
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{{Short description|Chemical compound}}
{{drugbox
{{Use dmy dates|date=March 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 443663022
| image = teduglutide.png
| alt =

<!-- Clinical data -->
| pronounce =
| tradename = Revestive, Gattex
| Drugs.com = {{drugs.com|monograph|teduglutide}}
| MedlinePlus =
| DailyMedID = Teduglutide
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = ]
| class =
| ATC_prefix = A16
| ATC_suffix = AX08
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-chemical-entities-australia-2017 | access-date=9 April 2023}}</ref><ref>{{cite web | title=Prescription medicines and biologicals: TGA annual summary 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-and-biologicals-tga-annual-summary-2017 | access-date=31 March 2024}}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Health Canada New Drug Authorizations: 2015 Highlights | website=] | date=4 May 2016 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-canada-new-drug-authorizations-2015-highlights.html | access-date=7 April 2024}}</ref>
| 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 = Rx-only
| legal_US_comment = <ref name="Gattex FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Revestive EPAR" /><ref name="Revestive EU PI" />
| 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 = 88%
| protein_bound =
| metabolism = ]
| metabolites =
| onset =
| elimination_half-life = 2h
| duration_of_action =
| excretion =

<!-- Identifiers -->
| CAS_number = 197922-42-2
| CAS_supplemental =
| PubChem = 16139605
| IUPHAR_ligand = 7049
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID = 17296109
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3Z9Y7UWC1J | UNII = 7M19191IKG
| KEGG_Ref = {{keggcite|correct|kegg}}
| verifiedrevid = 443291722
| KEGG = D06053
| IUPAC_name = 1-(4-methoxyphenyl)-7-oxo-6--4,5-<BR/>dihydropyrazolopyridine-<BR/>3-carboxamide
| ChEBI_Ref = {{ebicite|correct|EBI}}
| image = apixaban.png
| ChEBI = 72305
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8358471
| InChI = 1/C25H25N5O4/c1-34-19-11-9-18(10-12-19)30-23-20(22(27-30)24(26)32)13-15-29(25(23)33)17-7-5-16(6-8-17)28-14-3-2-4-21(28)31/h5-12H,2-4,13-15H2,1H3,(H2,26,32)
| smiles = O=C5N(c4ccc(N3C(=O)c1c(c(nn1c2ccc(OC)cc2)C(=O)N)CC3)cc4)CCCC5
| InChIKey = QNZCBYKSOIHPEH-UHFFFAOYAJ
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 231779 | ChEMBL =
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =

<!-- Chemical and physical data -->
| IUPAC_name = L-histidylglycyl-L-α-aspartylglycyl-L-seryl-L-phenylalanyl-L-seryl-L-α-aspartyl-L-α-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-α-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-α-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid
| C=164 | H=252 | N=44 | O=55 |S=1
| SMILES = CC(C)(NC(=O)(CC(C)C)NC(=O)(Cc1cc2ccccc12)NC(=O)(CC(N)=O)NC(=O)(NC(=O)(Cc1ccccc1)NC(=O)(CC(O)=O)NC(=O)(CCCNC(N)=N)NC(=O)(C)NC(=O)(C)NC(=O)(CC(C)C)NC(=O)(CC(N)=O)NC(=O)(CC(O)=O)NC(=O)(CC(C)C)NC(=O)(NC(=O)(NC(=O)(CC(N)=O)NC(=O)(CCSC)NC(=O)(CCC(O)=O)NC(=O)(CC(O)=O)NC(=O)(CO)NC(=O)(Cc1ccccc1)NC(=O)(CO)NC(=O)CNC(=O)(CC(O)=O)NC(=O)CNC(=O)(N)Cc1cnc1)(C)O)(C)CC)(C)CC)C(=O)N(CCC(N)=O)C(=O)N((C)O)C(=O)N(CCCCN)C(=O)N((C)CC)C(=O)N((C)O)C(=O)N(CC(O)=O)C(O)=O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C164H252N44O55S/c1-21-77(11)126(156(255)187-95(44-46-114(167)214)141(240)206-130(83(17)211)160(259)186-93(42-33-34-49-165)140(239)202-129(80(14)24-4)159(258)208-131(84(18)212)161(260)200-111(163(262)263)66-125(230)231)203-151(250)100(54-76(9)10)189-145(244)103(57-88-67-175-92-41-32-31-40-90(88)92)192-147(246)105(60-116(169)216)199-157(256)127(78(12)22-2)204-152(251)102(56-87-38-29-26-30-39-87)190-149(248)109(64-123(226)227)195-137(236)94(43-35-50-174-164(171)172)183-134(233)82(16)179-133(232)81(15)180-142(241)98(52-74(5)6)188-146(245)104(59-115(168)215)194-150(249)110(65-124(228)229)196-143(242)99(53-75(7)8)198-158(257)128(79(13)23-3)205-162(261)132(85(19)213)207-153(252)106(61-117(170)217)193-139(238)97(48-51-264-20)185-138(237)96(45-47-120(220)221)184-148(247)108(63-122(224)225)197-155(254)113(72-210)201-144(243)101(55-86-36-27-25-28-37-86)191-154(253)112(71-209)182-119(219)70-177-136(235)107(62-121(222)223)181-118(218)69-176-135(234)91(166)58-89-68-173-73-178-89/h25-32,36-41,67-68,73-85,91,93-113,126-132,175,209-213H,21-24,33-35,42-66,69-72,165-166H2,1-20H3,(H2,167,214)(H2,168,215)(H2,169,216)(H2,170,217)(H,173,178)(H,176,234)(H,177,235)(H,179,232)(H,180,241)(H,181,218)(H,182,219)(H,183,233)(H,184,247)(H,185,237)(H,186,259)(H,187,255)(H,188,245)(H,189,244)(H,190,248)(H,191,253)(H,192,246)(H,193,238)(H,194,249)(H,195,236)(H,196,242)(H,197,254)(H,198,257)(H,199,256)(H,200,260)(H,201,243)(H,202,239)(H,203,250)(H,204,251)(H,205,261)(H,206,240)(H,207,252)(H,208,258)(H,220,221)(H,222,223)(H,224,225)(H,226,227)(H,228,229)(H,230,231)(H,262,263)(H4,171,172,174)/t77-,78-,79-,80-,81-,82-,83+,84+,85+,91-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,126-,127-,128-,129-,130-,131-,132-/m0/s1
| StdInChI = 1S/C25H25N5O4/c1-34-19-11-9-18(10-12-19)30-23-20(22(27-30)24(26)32)13-15-29(25(23)33)17-7-5-16(6-8-17)28-14-3-2-4-21(28)31/h5-12H,2-4,13-15H2,1H3,(H2,26,32)
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QNZCBYKSOIHPEH-UHFFFAOYSA-N | StdInChIKey = CILIXQOJUNDIDU-ASQIGDHWSA-N
| density =
| CAS_number = 503612-47-3
| density_notes =
| ATC_prefix = none
| ATC_suffix = | melting_point =
| melting_high =
| PubChem = 10182969
| melting_notes =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| boiling_point =
| DrugBank = DB07828
| boiling_notes =
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03213 | solubility =
| sol_units =
| C=25 | H=25 | N=5 | O=4
| specific_rotation =
| molecular_weight = 459.497 g/mol
| bioavailability = ca. 50%
| protein_bound =
| metabolism =
| elimination_half-life = 9–14 h
| excretion = 75% ]y, 25% ]ly
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category=
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration = Oral
}} }}
'''Apixaban''' (manufacturer's designation BMS-562247-01) is a compound being investigated as an ]. It is a ]. It is presently undergoing phase III trials in the prevention of ], together with a number of related competing compounds, such as ].<ref>{{cite journal |author=Turpie AG |title=Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases |journal=Arterioscler. Thromb. Vasc. Biol. |volume=27 |issue=6 |pages=1238–47 |year=2007 |pmid=17379841 |doi=10.1161/ATVBAHA.107.139402}}</ref> It is being developed in a joint venture by ] and ].<ref>{{cite web |url=http://newsroom.bms.com/index.php?s=press_releases&item=254 |title=Bristol-Myers Squibb News Release 26 April 2007 |accessdate=2007-09-15 |format= |work=}}</ref><ref>{{cite web|last=Nainggolan|first=Lisa|title=Apixaban better than European enoxaparin regimen for preventing VTE|url=http://www.theheart.org/article/1052599.do|accessdate=1 April 2011}}</ref>

== Clinical trials ==

A 2007 trial showed that apixaban was equivalent to enoxaparin/open-label heparin in preventing thrombosis in patients who had undergone a knee replacement.<ref>{{cite journal |author=Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D |title=The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement |journal=J. Thromb. Haemost. |volume=5 |issue=12 |pages=2368–75 |year=2007 |pmid=17868430 |doi=10.1111/j.1538-7836.2007.02764.x}}</ref>


'''Teduglutide''', sold under the brand names '''Revestive''' (EU) and '''Gattex''' (US), is a 33-membered poly] and ] (GLP-2) analog that is used for the treatment of ]. It works by promoting ]l growth and possibly restoring ] and secretion.<ref name="pmid22570676">{{cite journal | vauthors = Jeppesen PB | title = Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome | journal = Therapeutic Advances in Gastroenterology | volume = 5 | issue = 3 | pages = 159–71 | date = May 2012 | pmid = 22570676 | pmc = 3342570 | doi = 10.1177/1756283X11436318 }}</ref> It was approved in both the European Union<ref name="Revestive EPAR">{{cite web | title=Revestive EPAR | website=] (EMA) | date=11 December 2001 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/revestive | access-date=20 March 2024}}</ref> and the United States in 2012.<ref name="Gattex FDA label">{{cite web | title=Gattex- teduglutide injection, powder, lyophilized, for solution; Gattex- teduglutide kit | website=DailyMed | date=28 February 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66b69c1e-b25c-44d3-b5ff-1c1de9a516fa | access-date=20 March 2024}}</ref>
A 2010 trial showed that apixaban was superior to enoxaparin in preventing thrombosis in patients undergoing elective hip replacement surgery, with similar bleeding rates.<ref>{{cite journal |doi=10.1056/NEJMoa1006885 |author=Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM, ADVANCE-3 Investigators |title=Apixaban versus enoxaparin for thromboprophylaxis after hip replacement |journal=N. Eng. J. Med. |volume=363 |issue=26 |pages=2487–98 |year=2010 |pmid=21175312}} </ref><ref>{{cite web|last=Nainggolan|first=Lisa|title=Apixaban better than European enoxaparin regimen for preventing VTE|url=http://www.theheart.org/article/1052599.do|publisher=http://www.theheart.org|accessdate=1 April 2011}}</ref>


==Medical uses==
A 2011 trial showed that in patients with atrial fibrillation who have failed or are not candidates for Vitamin K antagonist therapy, apixaban, as compared with aspirin, reduced the risk of stroke or systemic embolism in patients experiencing atrial fibrilation by more than 50% (from 3.7% per year with aspirin to 1.6% per year with Apixaban). Difference in death rates did not reach statistical significance.<ref name=Pfizer_2011>{{cite doi|10.1056/NEJMoa1007432}} </ref>
Up to a certain point, the gut can adapt to partial ]s that result in short bowel syndrome. Still, ] substitution of water, minerals and vitamins (depending on which part of the gut has been removed) is often necessary. Teduglutide may reduce or shorten the necessity of such infusions by improving the ] and possibly by other mechanisms.<ref name="Klement">{{cite journal| vauthors = Klement A | date = 5 January 2015| title = Das Kurzdarmsyndrom ist erstmals behandelbar: Revestive| journal = Österreichische Apothekerzeitung| issue = 1/2015| page = 20f| language = German}}</ref>


==Adverse effects==
A 2011 trial showed that patients receiving Apixaban after acute coronary syndrome suffered an increase rate of major bleeding episodes without a significant reduction in recurrent ischemic events.<ref>{{cite journal |author=Alexander, J. et al. |title=Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome |journal=New England Journal of Medicine |year=2011 |doi=10.1056/NEJMoa1105819}}</ref> For this reason, the trial was terminated early.
Common adverse effects in clinical studies included abdominal discomfort (49% of patients), ]s (28%), nausea (27%) and vomiting (14%), local reactions at the injection site (21%), and headache (17%).<ref name="Klement" />


==Chemistry and mechanism of action==
In a head to head study of apixaban versus ],<ref name="urlApixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation ClinicalTrials.gov">{{cite web | url = http://clinicaltrials.gov/ct2/show/study/NCT00412984?term=apixaban+aristotle&rank=1 | title = Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (ARISTOTLE) | format = | work = NCT00412984 | publisher = ClinicalTrials.gov | accessdate = 2011-06-23 }}</ref> apixaban meet both its primary endpoint (“noninferiority” to warfarin in preventing strokes) and a key secondary endpoint (superior compared to warfarin in avoiding major bleeding).<ref name="urlApixaban (Eliquis) Meets Primary Endpoint in ARISTOTLE « CardioBrief">{{cite web | url = http://cardiobrief.org/2011/06/22/apixaban-eliquis-meets-primary-endpoint-in-aristotle/ | title = ELIQUIS® (apixaban) Meets Primary and Key Secondary Endpoints in Phase 3 ARISTOTLE Study | author = Husten L | date = 2011-06-22 | format = | work = CardioBrief | publisher = WordPress.com | accessdate = 2011-06-23 }}</ref>
Teduglutide differs from natural GLP-2 by a single ]: an ] is replaced with a ]. This blocks breaking down of the molecule by ] and increases its half-life from seven minutes (GLP-2) to about two hours, while retaining its biological actions. These include maintenance of the intestinal mucosa, increasing intestinal blood flow, reducing ] and ] of gastric acid.<ref name="Klement" />


== Society and culture ==
==References==
=== Legal status ===
{{Reflist}}
It was approved in both the European Union (brand name Revestive)<ref name="Revestive EPAR" /><ref name="Revestive EU PI">{{cite web | title=Revestive Product information | website=Union Register of medicinal products | date=4 September 2012 | url=https://ec.europa.eu/health/documents/community-register/html/h787.htm | access-date=20 March 2024}}</ref> and the United States (brand name Gattex) in 2012.<ref name="Gattex FDA label" /> It was granted ] designation by the ] (EMA).<ref name="Revestive EPAR" /><ref name="Revestive EU PI" />


== References ==
{{Antithrombotics}}
{{blood-drug-stub}} {{reflist}}


{{Other alimentary tract and metabolism products}}
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