INTRODUCTION: Pulmonary arterial hypertension (PAH) is a chronic disorder of the 
pulmonary vasculature characterized by elevated mean pulmonary arterial pressure 
eventually leading to right-sided heart failure and premature death. Macitentan 
is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with 
high affinity and sustained receptor binding that was approved in the USA, 
Europe, Canada, and Switzerland for the treatment of PAH.
AREAS COVERED: This review discusses the pharmacokinetics (PK) and 
pharmacodynamics (PD) of macitentan and its drug interaction potential based on 
preclinical and clinical data.
EXPERT OPINION: Up to date, macitentan is the only registered treatment for PAH 
that significantly reduced morbidity and mortality as a combined endpoint in a 
long-term event-driven study. The safety profile of macitentan is favorable with 
respect to hepatic safety and edema/fluid retention and may be better than that 
of other ET receptor antagonists such as bosentan and ambrisentan. The PK 
profile supports a once-a-day dosing regimen. Macitentan has limited 
interactions with other drugs. Based on these characteristics macitentan is an 
important new addition to the treatment of PAH.