title: Riociguat: a novel new drug for treatment of pulmonary hypertension.
abstract: Riociguat is the first approved medication from the novel class of soluble guanylate cyclase (sGC) stimulators and the only agent approved for treating both chronic thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH). The novel mechanism of riociguat lies in its ability to restore the homeostatic and therapeutic effects of nitric oxide that are diminished as a result of phenotypic alterations associated with pulmonary hypertension (PH). Improvements in 6-minute walk distance (6MWD) in patients with PAH during the phase 3 PATENT-1 trial were comparable to other oral agents approved for the treatment of PAH. Improvements in 6MWD in patients with CTEPH during the phase 3 CHEST-1 trial were greater than those previously observed with other oral PAH-directed therapies. Hypotension is the dose-limiting adverse effect of riociguat and dose titration is performed gradually according to systolic blood pressure. Riociguat was tolerated at maximal doses by most patients during PATENT-1 and CHEST-1 and was well tolerated during long-term extension studies. Key factors to consider with riociguat are a patient's systolic blood pressure, drug interactions mediated by CYP1A1, CYP3A4, and P-glycoprotein, cost, and teratogenicity requiring enrollment in a Risk Evaluation and Mitigation Strategy program. Recently published guidelines recommend riociguat monotherapy as an option for treatment-naïve patients with World Health Organization Functional Class (WHO FC) II or III symptoms or as add-on therapy for patients with persistent WHO FC III or IV symptoms being treated with an ERA or inhaled prostanoid. Postmarketing experience and ongoing clinical investigations will further define the safety and role of riociguat in patients with PAH and other types of PH.
authors.affiliation: Department of Pharmacy Services, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Makowski
authors.affiliation: Division of Pulmonary and Critical Care, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Rissmiller
authors.affiliation: Department of Pharmacy Services, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Bullington
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat
keywords: pulmonary hypertension; riociguat; soluble guanylate cyclase