macitentan + riociguat

Macitentan + riociguat is an oral combination of two small molecule drugs used in the treatment of pulmonary arterial hypertension (PAH). Macitentan is an endothelin receptor antagonist that blocks endothelin A and B receptors to reduce vasoconstriction and cell proliferation associated with PAH[4]. Riociguat is a soluble guanylate cyclase (sGC) stimulator that both sensitizes sGC to endogenous nitric oxide and directly stimulates sGC independently of nitric oxide, leading to increased cGMP production, vasorelaxation, and antiproliferative effects[2][6][8]. The combination has demonstrated clinical and hemodynamic benefits in open-label and retrospective clinical studies as an initial, dual oral therapy in PAH, improving exercise capacity, WHO functional class, and hemodynamic parameters, with a favorable safety profile[1][3][7][9]. The combination is not approved as a unique, fixed-dose product but is used as co-administration of the individual agents.