Ambrisentan (U.S. trade name Letairis; E.U. trade name Volibris; India trade name Pulmonext by MSN labs) is a drug indicated for use in the treatment of pulmonary hypertension.[1][2]
The peptide endothelin constricts muscles in blood vessels, increasing blood pressure. Ambrisentan, which relaxes those muscles, is an endothelin receptor antagonist, and is selective for the type A endothelin receptor (ETA).[3] Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2).[4] Like all endothelin receptor antagonists, Ambrisentan is contraindicated in pregnant women as well as those who are trying to become pregnant, due to the potential for teratogenic effects on the fetus.[5] Patients who are on the Ambrisentan must enroll in the Ambrisentan (Letairis) REMS Program.[6]
Ambrisentan is indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.
Mechanism of actionedit
Ambrisentan is a drug that blocks endothelin, an endogenous hormone found in higher quantities in patients with pulmonary arterial hypertension. Endothelin binds to two receptors, ETA and ETB. ETA is responsible for cell growth in the vessels as well as vasoconstriction, while ETB plays a role in vasodilation, endothelin 1 clearance, and antiproliferation of cells.
Birth defectsedit
Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary system. In addition to this, endothelin receptors are also known to play a role in neural crest cell migration, growth, and differentiation. As such, endothelin receptor antagonists such as Ambrisentan are known to be teratogenic.
Ambrisentan has a high risk of liver damage, and of birth defects if a woman becomes pregnant while taking it. In the U.S., doctors who prescribe it, and patients who take it, must enroll in a special program, the LETAIRIS Education and Access Program (LEAP), to learn about those risks.[11] Ambrisentan is available only through specialty pharmacies.
Hepatic impairmentedit
Ambrisentan is not recommended in patients with moderate or severe hepatic impairment. The medication should also be discontinued if the liver aminotransferase enzymes for the patients are increased more than fivefold, or if the elevations are more than twofold and are accompanied by changes in bilirubin.[12]
Publicationsedit
This section needs to be updated. Please help update this article to reflect recent events or newly available information.(April 2020)
^"Letairis- ambrisentan tablet, film coated". DailyMed. 4 September 2019. Retrieved 18 April 2020.
^"Ambrisentan Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. 7 January 2019. Retrieved 18 April 2020.
^Vatter H, Seifert V (2006). "Ambrisentan, a non-peptide endothelin receptor antagonist". Cardiovascular Drug Reviews. 24 (1): 63–76. doi:10.1111/j.1527-3466.2006.00063.x. PMID 16939634.
^Frampton JE (August 2011). "Ambrisentan". American Journal of Cardiovascular Drugs. 11 (4): 215–26. doi:10.2165/11207340-000000000-00000. PMID 21623643.
^Galiè N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, et al. (June 2008). "Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2". Circulation. 117 (23): 3010–9. doi:10.1161/CIRCULATIONAHA.107.742510. PMID 18506008.
^"Clinical Results | Letairis® (ambrisentan)". www.letairis.com. Retrieved 24 October 2021.
^"Drug Approval Package: Letairis (Ambrisentan) NDA #022081". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 18 April 2020.
^"Ambrisentan Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). Retrieved 18 April 2020.
^Pollack A (16 June 2007). "Gilead's Drug Is Approved to Treat a Rare Disease". The New York Times. from the original on 24 May 2013. Retrieved 16 June 2007.
^"Clinical Results | Letairis® (ambrisentan)". www.letairis.com. Retrieved 24 October 2021.
^"Clinical Results | Letairis (ambrisentan)". www.letairis.com. Retrieved 24 October 2021.
^de Raaf MA, Beekhuijzen M, Guignabert C, Vonk Noordegraaf A, Bogaard HJ (2015). "Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension". Reproductive Toxicology. 56: 45–51. doi:10.1016/j.reprotox.2015.06.048. PMID 26111581.
^Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, et al. (August 2015). "Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension". The New England Journal of Medicine. 373 (9): 834–44. doi:10.1056/NEJMoa1413687. hdl:2445/97236. PMID 26308684.
External linksedit
"Ambrisentan". Drug Information Portal. U.S. National Library of Medicine.
ambrisentan, this, article, needs, additional, citations, verification, please, help, improve, this, article, adding, citations, reliable, sources, unsourced, material, challenged, removed, find, sources, news, newspapers, books, scholar, jstor, october, 2021,. This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Ambrisentan news newspapers books scholar JSTOR October 2021 Learn how and when to remove this template message Ambrisentan U S trade name Letairis E U trade name Volibris India trade name Pulmonext by MSN labs is a drug indicated for use in the treatment of pulmonary hypertension 1 2 AmbrisentanClinical dataTrade namesLetairis Volibris PulmonextAHFS Drugs comMonographMedlinePlusa612023License dataEU EMA by INN US DailyMed Ambrisentan US FDA AmbrisentanPregnancycategoryAU X High risk Routes ofadministrationOralATC codeC02KX02 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US only EU Rx only In general Prescription only Pharmacokinetic dataBioavailabilityUndeterminedProtein binding99 Elimination half life15 hours terminal IdentifiersIUPAC name 2S 2 4 6 dimethylpyrimidin 2 yl oxy 3 methoxy 3 3 diphenylpropanoic acidCAS Number177036 94 1 YPubChem CID6918493IUPHAR BPS3951DrugBankDB06403 YChemSpider5293690 YUNIIHW6NV07QECKEGGD07077ChEBICHEBI 135949ChEMBLChEMBL1111 YCompTox Dashboard EPA DTXSID4046282ECHA InfoCard100 184 855Chemical and physical dataFormulaC 22H 22N 2O 4Molar mass378 428 g mol 13D model JSmol Interactive imageSMILES O C O C H Oc1nc cc n1 C C C OC c2ccccc2 c3ccccc3InChI InChI 1S C22H22N2O4 c1 15 14 16 2 24 21 23 15 28 19 20 25 26 22 27 3 17 10 6 4 7 11 17 18 12 8 5 9 13 18 h4 14 19H 1 3H3 H 25 26 t19 m1 s1 YKey OUJTZYPIHDYQMC LJQANCHMSA N Y verify The peptide endothelin constricts muscles in blood vessels increasing blood pressure Ambrisentan which relaxes those muscles is an endothelin receptor antagonist and is selective for the type A endothelin receptor ETA 3 Ambrisentan significantly improved exercise capacity 6 minute walk distance compared with placebo in two double blind multicenter trials ARIES 1 and ARIES 2 4 Like all endothelin receptor antagonists Ambrisentan is contraindicated in pregnant women as well as those who are trying to become pregnant due to the potential for teratogenic effects on the fetus 5 Patients who are on the Ambrisentan must enroll in the Ambrisentan Letairis REMS Program 6 Ambrisentan was approved by the U S Food and Drug Administration FDA and the European Medicines Agency EMA and designated an orphan drug for the treatment of pulmonary hypertension 7 8 9 10 Contents 1 Clinical uses 2 Mechanism of action 3 Birth defects 4 Hepatic impairment 5 Publications 6 References 7 External linksClinical uses editAmbrisentan is indicated for the treatment of pulmonary arterial hypertension WHO Group 1 in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening Mechanism of action editAmbrisentan is a drug that blocks endothelin an endogenous hormone found in higher quantities in patients with pulmonary arterial hypertension Endothelin binds to two receptors ETA and ETB ETA is responsible for cell growth in the vessels as well as vasoconstriction while ETB plays a role in vasodilation endothelin 1 clearance and antiproliferation of cells Birth defects editEndothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart These physiologic effects are vital for the development of the fetal cardiopulmonary system In addition to this endothelin receptors are also known to play a role in neural crest cell migration growth and differentiation As such endothelin receptor antagonists such as Ambrisentan are known to be teratogenic Ambrisentan has a high risk of liver damage and of birth defects if a woman becomes pregnant while taking it In the U S doctors who prescribe it and patients who take it must enroll in a special program the LETAIRIS Education and Access Program LEAP to learn about those risks 11 Ambrisentan is available only through specialty pharmacies Hepatic impairment editAmbrisentan is not recommended in patients with moderate or severe hepatic impairment The medication should also be discontinued if the liver aminotransferase enzymes for the patients are increased more than fivefold or if the elevations are more than twofold and are accompanied by changes in bilirubin 12 Publications editThis section needs to be updated Please help update this article to reflect recent events or newly available information April 2020 Last updated 9 2 20158 15 2015 Reprod Toxicol Endothelin receptor activation mediates strong pulmonary vasoconstriction and positive inotropic effect on the heart These physiologic effects are vital for the development of the fetal cardiopulmonary system As such endothelin receptor antagonists such as ambrisentan are teratogenic 13 8 27 2015 NEJM Ambrisentan when used in combination therapy with tadalafil was found to be more efficacious in treating treatment naive patients with WHO class II or III pulmonary arterial hypertension than monotherapy using either drug 14 References edit Letairis ambrisentan tablet film coated DailyMed 4 September 2019 Retrieved 18 April 2020 Ambrisentan Monograph for Professionals Drugs com American Society of Health System Pharmacists 7 January 2019 Retrieved 18 April 2020 Vatter H Seifert V 2006 Ambrisentan a non peptide endothelin receptor antagonist Cardiovascular Drug Reviews 24 1 63 76 doi 10 1111 j 1527 3466 2006 00063 x PMID 16939634 Frampton JE August 2011 Ambrisentan American Journal of Cardiovascular Drugs 11 4 215 26 doi 10 2165 11207340 000000000 00000 PMID 21623643 Galie N Olschewski H Oudiz RJ Torres F Frost A Ghofrani HA et al June 2008 Ambrisentan for the treatment of pulmonary arterial hypertension results of the ambrisentan in pulmonary arterial hypertension randomized double blind placebo controlled multicenter efficacy ARIES study 1 and 2 Circulation 117 23 3010 9 doi 10 1161 CIRCULATIONAHA 107 742510 PMID 18506008 Clinical Results Letairis ambrisentan www letairis com Retrieved 24 October 2021 Drug Approval Package Letairis Ambrisentan NDA 022081 U S Food and Drug Administration FDA 24 December 1999 Retrieved 18 April 2020 Volibris EPAR European Medicines Agency EMA 17 September 2018 Retrieved 18 April 2020 Ambrisentan Orphan Drug Designation and Approval U S Food and Drug Administration FDA Retrieved 18 April 2020 Pollack A 16 June 2007 Gilead s Drug Is Approved to Treat a Rare Disease The New York Times Archived from the original on 24 May 2013 Retrieved 16 June 2007 Clinical Results Letairis ambrisentan www letairis com Retrieved 24 October 2021 Clinical Results Letairis ambrisentan www letairis com Retrieved 24 October 2021 de Raaf MA Beekhuijzen M Guignabert C Vonk Noordegraaf A Bogaard HJ 2015 Endothelin 1 receptor antagonists in fetal development and pulmonary arterial hypertension Reproductive Toxicology 56 45 51 doi 10 1016 j reprotox 2015 06 048 PMID 26111581 Galie N Barbera JA Frost AE Ghofrani HA Hoeper MM McLaughlin VV et al August 2015 Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension The New England Journal of Medicine 373 9 834 44 doi 10 1056 NEJMoa1413687 hdl 2445 97236 PMID 26308684 External links edit Ambrisentan Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Ambrisentan amp oldid 1170995803, wikipedia, wiki, book, books, library,
