Macitentan is a novel dual endothelin receptor antagonist (ERA)
showing sustained receptor occupancy
Author: Jasper Dingemanse†, Patricia N Sidharta, Willis C Maddrey, Lewis J Rubin & Hani Mickail
Published: March 01, 2014
Number of pages:15
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.
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.
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