{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:05:45Z","timestamp":1791104745179,"version":"4.1.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>Objective: To review the pharmacology, safety, and efficacy of macitentan. Data Sources: PubMed, EMBASE, and ClinicalTrials.gov were searched using the terms macitentan and ACT-064992. Study Selection and Data Extraction: Phase II and III trials were reviewed in our primary analysis; data from phase I trials and other studies were reported as applicable. Data Synthesis: Macitentan is a dual endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). Current treatment options for PAH include 2 other ERAs, phosphodiesterase type 5 inhibitors, prostanoids, and calcium channel blockers. Recently published guidelines do not assert a preference for individual agents. Two trials evaluated the safety and efficacy of macitentan. The phase II study was a 12-month placebo-controlled trial involving patients with idiopathic pulmonary fibrosis; the primary end point was change in forced vital capacity. No significant treatment effect was observed. The phase III study was a placebo-controlled trial involving patients with PAH. The primary end point was time to first occurrence of a composite of outcomes, including all-cause death and PAH worsening. Over a median period of 115 weeks, macitentan 10 mg and 3 mg daily significantly reduced morbidity and mortality. Commonly reported adverse effects included worsening of PAH, peripheral edema, upper-respiratory-tract infection, and anemia. Conclusions: Macitentan represents the latest addition to the PAH armamentarium. Compared with other ERAs, clinical advantages may include fewer contraindications, use in hepatic impairment, and once-daily administration. However, further comparative studies are necessary to ascertain its place in therapy.<\/jats:p>","DOI":"10.1177\/1060028013518900","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T23:59:14Z","timestamp":1390521554000},"page":"538-547","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Macitentan for the Treatment of Pulmonary Arterial Hypertension"],"prefix":"10.1177","volume":"48","author":[{"given":"Irene S.","family":"Hong","sequence":"first","affiliation":[{"name":"University at Buffalo, The State University of New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly V.","family":"Coe","sequence":"additional","affiliation":[{"name":"University at Buffalo, The State University of New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Catanzaro","sequence":"additional","affiliation":[{"name":"University at Buffalo, The State University of New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,1,23]]},"reference":[{"key":"bibr1-1060028013518900","unstructured":"Centers for Disease Control and Prevention. Pulmonary hypertension factsheet. http:\/\/www.cdc.gov. Accessed October 24, 2013."},{"key":"bibr2-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.032"},{"key":"bibr3-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.011"},{"key":"bibr4-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.012"},{"key":"bibr5-1060028013518900","unstructured":"National Heart Blood, Lung, and Blood Institute. What is pulmonary hypertension? http:\/\/www.nhlbi.nih.gov\/health\/health-topics\/topics\/pah\/. Accessed October 24, 2013."},{"key":"bibr6-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040291"},{"key":"bibr7-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.847707"},{"key":"bibr8-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.01.004"},{"key":"bibr9-1060028013518900","unstructured":"Opsumit\u00ae (macitentan) tablets [product information]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc; 2013."},{"key":"bibr10-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp297"},{"key":"bibr11-1060028013518900","unstructured":"Tyvaso(r) (treprostinil) inhalation solution [product information]. Research Triangle Park, NC: United Therapeutics Corp; 2013."},{"key":"bibr12-1060028013518900","unstructured":"US Food and Drug Administration (FDA). Drugs@FDA. http:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/index.cfm. Accessed November 20, 2013."},{"key":"bibr13-1060028013518900","unstructured":"CenterWatch. Pulmonary arterial hypertension. http:\/\/www.centerwatch.com\/clinical-trials\/results\/new-therapies\/nmt-details.aspx?CatID=702. Accessed October 27, 2013."},{"key":"bibr14-1060028013518900","unstructured":"Adempas\u00ae (riociguat) tablets [product information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc; 2013."},{"key":"bibr15-1060028013518900","unstructured":"Formulary\u00ae. Pfizer voluntarily withdraws sitaxsentan from the market worldwide and halts ongoing clinical trials. http:\/\/formularyjournal.modernmedicine.com\/formulary-journal\/news\/clinical\/clinical-pharmacology\/pfizer-voluntarily-withdraws-sitaxsentan-marke. Accessed October 29, 2013."},{"key":"bibr16-1060028013518900","unstructured":"US Food and Drug Administration (FDA). FDA approves Opsumit\u00ae to treat pulmonary arterial hypertension. http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm371362.htm. Accessed October 29, 2013."},{"key":"bibr17-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1021\/jm3009103"},{"key":"bibr18-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.142976"},{"key":"bibr19-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.152"},{"key":"bibr20-1060028013518900","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2012.664665"},{"key":"bibr21-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.193"},{"key":"bibr22-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1159\/000351704"},{"key":"bibr23-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213917"},{"key":"bibr24-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1043-2"},{"key":"bibr25-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00104612"},{"key":"bibr26-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213917"},{"key":"bibr27-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201201-0006PP"},{"key":"bibr28-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200705-200732OC"},{"key":"bibr29-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201011-1874OC"},{"key":"bibr30-1060028013518900","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-9-201305070-00003"},{"key":"bibr31-1060028013518900","unstructured":"ClinicalTrials.gov. Long-term extension study of the SERAPHIN study, to assess the safety and tolerability of ACT 064992 in patients with symptomatic pulmonary arterial hypertension (SERAPHIN OL). http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT00667823?term=macitentan&rank=11. Accessed October 27, 2013."},{"key":"bibr32-1060028013518900","unstructured":"ClinicalTrials.gov. SYMPHONY: a study of macitentan in pulmonary arterial hypertension to validate the PAH-SYMPACT. http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01841762?term=macitentan&rank=5. Accessed October 27, 2013."},{"key":"bibr33-1060028013518900","unstructured":"ClinicalTrials.gov. AC-055-402: an extension of AC-055-401, study of macitentan in patients with PAH to psychometrically validate PAH-SYMPACT instrument (SYMPHONYext). http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01847014?term=macitentan&rank=8. Accessed October 27, 2013."},{"key":"bibr34-1060028013518900","unstructured":"ClinicalTrials.gov. MAESTRO (Macitentan in eisenmenger syndrome to restore exercise capacity). http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01743001?term=macitentan&rank=7. Accessed October 27, 2013."},{"key":"bibr35-1060028013518900","first-page":"455","volume":"27","author":"Corallo C","year":"2013","journal-title":"J Biol Regul Homeost Agents"},{"key":"bibr36-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.03.032"},{"key":"bibr37-1060028013518900","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.22959"},{"key":"bibr38-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1593\/neo.10806"},{"key":"bibr39-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1593\/tlo.11286"},{"key":"bibr40-1060028013518900","unstructured":"ClinicalTrials.gov. Macitentan for the treatment of digital ulcers in systemic sclerosis patients (DUAL-1). http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01474109?term=macitentan&rank=1. Accessed October 27, 2013."},{"key":"bibr41-1060028013518900","unstructured":"ClinicalTrials.gov. Macitentan in combo with dose-dense temozolomide in patients with recurrent glioblastoma. http:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01499251?term=macitentan&rank=4. Accessed October 27, 2013."},{"key":"bibr42-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9316-3"},{"key":"bibr43-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.01.010"},{"key":"bibr44-1060028013518900","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0063-8"},{"key":"bibr45-1060028013518900","unstructured":"Letairis\u00ae (ambrisentan) tablets [product information]. Foster City, CA: Gilead Sciences, Inc; 2013."},{"key":"bibr46-1060028013518900","unstructured":"Tracleer\u00ae (bosentan) tablets [product information]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc; 2012."},{"key":"bibr47-1060028013518900","unstructured":"US Food and Drug Administration (FDA). Orange Book: approved drug products with therapeutic equivalence equations. http:\/\/www.accessdata.fda.gov\/scripts\/cder\/ob\/default.cfm. Accessed October 27, 2013."},{"key":"bibr48-1060028013518900","unstructured":"Ambrisentan. Red Book Online\u00ae. Truven Health Analytics. Accessed October 27, 2013. http:\/\/www.micromedexsolutions.com\/micromedex2\/librarian\/"},{"key":"bibr49-1060028013518900","unstructured":"Bosentan. Red Book Online\u00ae. Truven Health Analytics. Accessed October 27, 2013. http:\/\/www.micromedexsolutions.com\/micromedex2\/librarian\/"},{"key":"bibr50-1060028013518900","unstructured":"Macitentan. Red Book Online\u00ae. Truven Health Analytics. 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