INTRODUCTION: 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.
AREAS COVERED: This drug evaluation reviews the efficacy, safety and clinical 
pharmacology of macitentan in the treatment of PAH.
EXPERT OPINION: 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.