Drug Interactions between 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 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 1/3 to 1/10 the pharmacologic activity of riociguat, were reduced by approximately 50% and 25%, respectively.

MANAGEMENT: Caution is advised if riociguat is prescribed in combination with potent, dual multi-pathway CYP450 and P-gp/BCRP inhibitors such as itraconazole, ketoconazole, and some HIV protease inhibitors. Some authorities recommend avoiding concomitant use of riociguat during and for 2 weeks after treatment with itraconazole. However, if concomitant use is necessary, a starting dosage of riociguat 0.5 mg three times a day should be considered, and patients should be monitored for signs and symptoms of hypotension.

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