title: Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension.
abstract: BACKGROUND
  Macitentan is a novel dual endothelin receptor antagonist (ERA) showing sustained receptor occupancy. In vitro and in vivo animal studies have demonstrated its potency in antagonizing endothelin-induced disorders. A large morbidity/mortality study in patients with pulmonary arterial hypertension (PAH) taking macitentan has been completed recently.
  
  
  METHODS
  This drug evaluation reviews the efficacy, safety and clinical pharmacology of macitentan in the treatment of PAH.
  
  
  CONCLUSIONS
  The large Phase III study (SERAPHIN) tested macitentan in more than 700 PAH patients and has provided unique long-term outcome data for this ERA, not available for other members of this class. The effect on a composite clinically relevant morbidity/mortality end point was highly significant at a 10 mg/day dose. The safety profile of macitentan appears to be superior with respect to hepatic safety and edema/fluid retention than bosentan and ambrisentan, respectively, and is similar when considering decrease in hemoglobin concentration. The drug has a low propensity for drug-drug interactions and has one circulating pharmacologically active metabolite. The pharmacokinetics of macitentan in patients with renal or hepatic impairment does not require dose adjustments. Based on its characteristics, macitentan is an important addition to the therapeutic armamentarium in the long-term treatment of PAH. Its potential use in other disorders is under investigation.
authors.affiliation: Actelion Pharmaceuticals Ltd, Departments of Clinical Pharmacology and Global Drug Safety , Gewerbestrasse 16, 4123 Allschwil , Switzerland +41 61 565 6463 ; +41 61 565 6200 ; jasper.dingemanse@actelion.com.
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Sidharta
authors.forename: Willis C
authors.initials: WC
authors.lastname: Maddrey
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.forename: Hani
authors.initials: H
authors.lastname: Mickail
mesh_terms: D000818:Animals; D065128:Endothelin Receptor Antagonists; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D065128:Endothelin Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan