Drug Interaction Report

MONITOR: Coadministration with niraparib may increase the plasma concentrations of drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism is BCRP inhibition by niraparib. In vitro studies have shown that niraparib is able to inhibit BCRP, but a clinically meaningful interaction is unlikely.

MANAGEMENT: Caution is recommended if niraparib is used in combination with substrates of the breast cancer resistance protein (BCRP) transporter such as irinotecan, rosuvastatin, simvastatin, atorvastatin, and/or methotrexate. Monitoring for signs and symptoms of increased exposure to the BCRP substrate should be considered whenever niraparib is added to or withdrawn from therapy.

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.