CardioSource WorldNews October 2015 | Page 32

What is the role of nitric oxide (NO) in PAH and CTEPH? • PAH and CTEPH are associated with impaired synthesis of NO, endothelial dysfunction, and insufficient stimulation of the NO-sGCcGMP pathway • Intracellular cyclic guanosine monophosphate (cGMP) plays an important role in regulating processes that influence vascular tone, proliferation, fibrosis, and inflammation Adempas stimulates sGC regardless of NO level to produce more cGMP IN THE PRESENCE OF • Adempas sensitizes soluble guanylate cyclase (sGC) to endogenous NO by stabilizing sGC-NO binding • Adempas directly stimulates sGC independently of NO via a different binding site • Increased cGMP leads to vasodilation N O sGC sGC Adempas cGMP cGMP vasodilation INDEPENDENTLY OF INDICATIONS • Adempas (riociguat) tablets are indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), (WHO Group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class. • Adempas is indicated for the treatment of adults with pulmonary arterial hypertension (PAH), (WHO Group 1), to improve exercise capacity, WHO functional class and to delay clinical worsening.* Efficacy was shown in patients on Adempas monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominantly patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%). *Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of pulmonary hypertension, start of new PAH-specific treatment, persistent decrease in 6MWD and persistent worsening of WHO functional class. N O IMPORTANT SAFETY INFORMATION WARNING: EMBRYO-FETAL TOXICITY Do not administer Adempas (riociguat) tablets to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception. For all female patients, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program. CONTRAINDICATIONS Adempas is contraindicated in: • Pregnancy. Adempas may cause fetal harm when administered to a pregnant woman. Adempas was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus • Co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form. Please see additional Important Safety Information, including Boxed Warning, throughout and Brief Summary of Prescribing Information at end of advertisement.