macitentan + tadalafil + selexipag

A fixed-dose **combination of macitentan, tadalafil, and selexipag** is an investigational triple oral therapy for **pulmonary arterial hypertension (PAH)**. All three agents target distinct, guideline-recommended pathways involved in PAH pathogenesis: macitentan is an endothelin receptor antagonist that reduces vasoconstriction and pathological vascular remodeling; tadalafil is a phosphodiesterase-5 inhibitor that potentiates vasodilation via increased cGMP signaling; selexipag is a selective prostacyclin (IP) receptor agonist promoting vasodilation and exerting antiproliferative and antifibrotic effects. Combining these drugs aims to maximize efficacy by targeting multiple mechanisms underlying pulmonary vascular resistance and right heart dysfunction in PAH patients[1][2][4][5]. Triple oral therapy with these agents is under clinical investigation to assess safety and efficacy, in particular compared to dual oral therapy regimens.