Drug Interaction Report

ADJUST DOSING INTERVAL: Concurrent administration of riociguat with antacids may reduce its gastrointestinal absorption. Riociguat exhibits pH-dependent solubility, with increased solubility at lower pH. According to the product labeling, administration of riociguat with an antacid containing aluminum hydroxide and magnesium hydroxide resulted in decreases of mean riociguat peak plasma concentration (Cmax) and systemic exposure (AUC) by 56% and 34%, respectively. The Cmax and AUC of the active metabolite, M1, which has 1/10th to 1/3rd the pharmacologic activity of riociguat, were similarly reduced..

MANAGEMENT: Antacids should be taken at least 2 hours before or 1 hour after riociguat.

ADJUST DOSE: Smoking may decrease the plasma concentrations of riociguat. The proposed mechanism is induction of the CYP450 1A1-mediated metabolism of riociguat by polycyclic aromatic hydrocarbons present in cigarette smoke. CYP450 1A1 is responsible for the formation of the major active metabolite, M1, which has just 1/3 to 1/10 the pharmacologic activity of riociguat. According to the product labeling, plasma concentrations of riociguat are reduced by 50% to 60% in smokers compared to nonsmokers.

MANAGEMENT: Patients should be advised to stop smoking. Riociguat dosages higher than 2.5 mg three times a day may be considered in cigarette smokers, if tolerated, to match the exposure seen in nonsmoking patients. However, safety and effectiveness of higher dosages have not been established. A dosage reduction should be considered in patients who stop smoking during treatment with riociguat. The tablet form of riociguat can generally be taken with or without food. Some authorities recommend not to switch between fed and fasted riociguat intake because of increased peak plasma levels of riociguat in the fasting compared to the fed state.