Drug Interaction Report

ADJUST DOSING INTERVAL: Loracarbef may exhibit reduced gastrointestinal absorption in the presence of food. When loracarbef capsules were administered with food, the peak plasma concentrations were 50% to 60% of concentrations after administration in a fasting state and were reached 30 to 60 minutes later. Area under the concentration-time curve (AUC) was not affected. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: Loracarbef should be administered at least one hour before or two hours after eating.

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.