lomitapide

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 444364270

| image = Lomitapide_skeletal.svg

| pronounce =

| tradename = Juxtapid (US), Lojuxta (EU)

| Drugs.com =

| MedlinePlus =

| licence_EU = yes

| DailyMedID = Lomitapide

| licence_US = Lomitapide

| pregnancy_AU =

| pregnancy_category =

| routes_of_administration = By mouth

| ATC_prefix = C10

| ATC_suffix = AX12

| ATC_supplemental =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US = Rx-only

| legal_US_comment = {{cite web | title=Juxtapid- lomitapide mesylate capsule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e4c45bb5-15f4-437e-ab98-a649b3676d14 | access-date=27 January 2021}}

| legal_EU = Rx-only

| legal_EU_comment =

| legal_status =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| index2_label = mesylate

| IUPHAR_ligand = 7439

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 182431-12-5

| CAS_number2 = 202914-84-9

| PubChem = 9853053

| PubChem2 = 11274333

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB08827

| DrugBank2 = DBSALT000110

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 8028764

| ChemSpiderID2 = 9449335

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 82KUB0583F

| UNII2 = X4S83CP54E

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D09637

| KEGG2 = D09638

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 72297

| ChEBI2 = 72299

| ChEMBL = 354541

| ChEMBL2 = 2105662

| synonyms = AEGR-773, BMS-201038

| IUPAC_name = N-(2,2,2-Trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]2-yl]carbonyl]amino]-1-piperidinyl]butyl]-9H-fluoren-9-carboxamide

| C=39 | H=37 | F=6 | N=3 | O=2

| smiles = FC(F)(F)c5ccc(cc5)-c1ccccc1C(=O)NC4CCN(CC4)CCCCC2(C(=O)NCC(F)(F)F)c3ccccc3-c6ccccc26

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C39H37F6N3O2/c40-38(41,42)25-46-36(50)37(33-13-5-3-10-30(33)31-11-4-6-14-34(31)37)21-7-8-22-48-23-19-28(20-24-48)47-35(49)32-12-2-1-9-29(32)26-15-17-27(18-16-26)39(43,44)45/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49)

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = MBBCVAKAJPKAKM-UHFFFAOYSA-N

}}

Lomitapide , sold under the brand name Juxtapid in the US and Lojuxta in the EU, is a medication used as a lipid-lowering agent for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals.{{cite journal

| author = H. Spreitzer

| date = 12 March 2007

| title = Neue Wirkstoffe – BMS-201038

| journal = Österreichische Apothekerzeitung

| issue = 6/2007

| pages = 268

| language = German

}} It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate.{{cite journal | vauthors = Horwich TB, Fonarow GC | title = Measures of obesity and outcomes after myocardial infarction | journal = Circulation | volume = 118 | issue = 5 | pages = 469–71 | date = July 2008 | pmid = 18663098 | doi = 10.1161/CIRCULATIONAHA.108.792689 | doi-access = free }}{{cite web | url = http://www.pr-inside.com/aegerion-pharmaceuticals-inc-announces-aegr-r904473.htm | title = Aegerion Pharmaceuticals, Inc. Announces AEGR-733 Phase II Data Demonstrates Significant Lowering of LDL Cholesterol with Promising Hepatic Safety Profile | work = Business Wire | date = 9 November 2008 | archive-url = https://web.archive.org/web/20120229092512/http://www.pr-inside.com/aegerion-pharmaceuticals-inc-announces-aegr-r904473.htm | archive-date=2012-02-29 }}

The US Food and Drug Administration (FDA) approved lomitapide in December 2012, as an orphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in people with homozygous familial hypercholesterolemia (HoFH).{{cite web | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm | archive-url = https://web.archive.org/web/20130128180135/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm | archive-date = 28 January 2013 | title = FDA approves new orphan drug for rare cholesterol disorder | publisher = U.S. Food and Drug Administration }}

In July 2013, the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adults with HoFH.{{cite web | title=Lojuxta EPAR | website=European Medicines Agency (EMA) | date=3 September 2013 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lojuxta | access-date=27 January 2021}}

Mechanism of action

Lomitapide inhibits the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.{{cite journal | vauthors = Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ | display-authors = 6 | title = Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia | journal = The New England Journal of Medicine | volume = 356 | issue = 2 | pages = 148–56 | date = January 2007 | pmid = 17215532 | doi = 10.1056/NEJMoa061189 | doi-access = free }}

In December 2012, drug manufacturer Aegerion announced they had been approved by the FDA to as "an adjunct to a low-fat diet and other lipid-lowering treatments...in patients with homozygous familial hypercholesterolemia (HoFH)."{{cite web|title=FDA Approves Juxtapid for Homozygous Familial Hypercholesteolemia|url=http://www.dailyrx.com/juxtapid-reduces-cholesterol-patients-homozygous-familial-hypercholesterolemia|date=26 December 2012|access-date=1 January 2013|archive-url=https://web.archive.org/web/20121229140605/http://www.dailyrx.com/juxtapid-reduces-cholesterol-patients-homozygous-familial-hypercholesterolemia|archive-date=29 December 2012|url-status=dead}}{{cite press release | url = http://ir.aegerion.com/releasedetail.cfm?ReleaseID=728650 | title = FDA Approves Aegerion Pharmaceuticals' Juxtapid (lomitapide) Capsules for Homozygous Familial Hypercholesterolemia (HoFH) | publisher = Aegerion Pharmaceuticals | date = 24 December 2012 | access-date = 1 January 2013 | archive-url = https://web.archive.org/web/20160922115515/http://ir.aegerion.com/releasedetail.cfm?releaseid=728650 | archive-date = 22 September 2016 | url-status = dead }}

Side effects

In a Phase III study, lomitapide led to elevated aminotransferase levels and fat accumulation in the liver.

References

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