Riociguat (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ADEMPAS
- RIOCIGUAT
Boxed Warning
Do not administer Adempas to a pregnant female because it may cause fetal harm [see Contraindications (4.1), Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after [see Dosage and Administration (2.3), Warnings and Precautions (5.1, 5.2),and Use in Specific Populations (8.3)]. For all female patients, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program [see Warnings and Precautions (5.1, 5.2)].
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in the labeling: •Embryo-Fetal Toxicity [see Warnings and Precautions (5.1)] •Hypotension [see Warnings and Precautions (5.3)] •Bleeding [see Warnings and Precautions (5.4)]
Mechanism of Action
Riociguat is a stimulator of soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme catalyzes synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). Intracellular cGMP plays an important role in regulating processes that influence vascular tone, proliferation, fibrosis and inflammation. Pulmonary hypertension is associated with endothelial dysfunction, impaired synthesis of nitric oxide and insufficient stimulation of the NO-sGC-cGMP pathway. Riociguat has a dual mode of action. It sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation. The active metabolite (M1) of riociguat is 1/3 to 1/10 as potent as riociguat.
Overdosage
In cases of overdose, blood pressure should be closely monitored and supported as appropriate. Based on extensive plasma protein binding, riociguat is not expected to be dialyzable.