Drug Interactions between atazanavir / cobicistat and riociguat

ADJUST DOSE: Coadministration with drugs that are both potent multi-pathway CYP450 and P-glycoprotein/breast cancer resistant protein (P-gp/BCRP) inhibitors may significantly increase the plasma concentrations of riociguat, which is primarily metabolized by CYP450 1A1, 3A, 2C8 and 2J2, and is also a substrate of the P-gp/BCRP efflux transporter. Increased levels of riociguat may increase the risk for hypotension. According to the product labeling, administration of riociguat with the potent CYP450 and P-gp/BCRP inhibitor ketoconazole resulted in increases of riociguat peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 1.5- and 2.5-fold, respectively. The Cmax and AUC of the active metabolite, M1, which has 1/10th to 1/3rd the pharmacologic activity of riociguat, were reduced by approximately 50% and 25%, respectively.

MANAGEMENT: The initiation of drugs that are both potent multi-pathway CYP450 and P-gp/BCRP inhibitors such as itraconazole, ketoconazole, and some HIV protease inhibitors in patients on stable doses of riociguat is not recommended. Some authorities recommend avoiding concomitant use of riociguat during and for 2 weeks after treatment with itraconazole. When riociguat is initiated in patients on stable doses of strong multi pathway CYP450 (especially CYP450 1A1 and CYP450 3A4) and P-gp/BCRP inhibitors, consider a dosage of riociguat of 0.5 mg three times a day and monitor these patients for signs and symptoms of hypotension. Clinical data and dosing adjustment recommendations for riociguat are not currently available for children receiving concomitant systemic treatment with strong CYP450 and P-gp/BCRP inhibitors.

ADJUST DOSE: Coadministration with drugs that are both potent multi-pathway CYP450 and P-glycoprotein/breast cancer resistant protein (P-gp/BCRP) inhibitors may significantly increase the plasma concentrations of riociguat, which is primarily metabolized by CYP450 1A1, 3A, 2C8 and 2J2, and is also a substrate of the P-gp/BCRP efflux transporter. Increased levels of riociguat may increase the risk for hypotension. According to the product labeling, administration of riociguat with the potent CYP450 and P-gp/BCRP inhibitor ketoconazole resulted in increases of riociguat peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 1.5- and 2.5-fold, respectively. The Cmax and AUC of the active metabolite, M1, which has 1/10th to 1/3rd the pharmacologic activity of riociguat, were reduced by approximately 50% and 25%, respectively.

MANAGEMENT: The initiation of drugs that are both potent multi-pathway CYP450 and P-gp/BCRP inhibitors such as itraconazole, ketoconazole, and some HIV protease inhibitors in patients on stable doses of riociguat is not recommended. Some authorities recommend avoiding concomitant use of riociguat during and for 2 weeks after treatment with itraconazole. When riociguat is initiated in patients on stable doses of strong multi pathway CYP450 (especially CYP450 1A1 and CYP450 3A4) and P-gp/BCRP inhibitors, consider a dosage of riociguat of 0.5 mg three times a day and monitor these patients for signs and symptoms of hypotension. Clinical data and dosing adjustment recommendations for riociguat are not currently available for children receiving concomitant systemic treatment with strong CYP450 and P-gp/BCRP inhibitors.