levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.aluminum hydroxide/magnesium trisilicateMonitor Closely (1)aluminum hydroxide/magnesium trisilicate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.amiodaroneSerious - Use Alternative (1)amiodarone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededamobarbitalSerious - Use Alternative (1)amobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.amyl nitriteContraindicated (1)amyl nitrite, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.anastrozoleMinor (1)anastrozole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.apalutamideMonitor Closely (1)apalutamide will decrease the level or effect of riociguat by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.Serious - Use Alternative (1)apalutamide will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.aspirin/citric acid/sodium bicarbonateMonitor Closely (1)aspirin/citric acid/sodium bicarbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.atazanavirMonitor Closely (1)atazanavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 0.5 mg 3 times a day when initiating riociguat in patients receiving atazanavir (a strong CYP3A4 and P-gp inhibitor). Monitor for signs and symptoms of hypotension on initiation and on treatment with atazanavir.atorvastatinSerious - Use Alternative (1)atorvastatin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededavanafilContraindicated (1)avanafil, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.azithromycinSerious - Use Alternative (1)azithromycin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededbenazeprilMonitor Closely (1)riociguat, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.berotralstatMonitor Closely (1)berotralstat will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.bosentanMonitor Closely (1)bosentan will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentcalcium carbonateMonitor Closely (1)calcium carbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.cannabidiolMonitor Closely (1)cannabidiol will increase the level or effect of riociguat by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.captoprilMonitor Closely (1)riociguat increases effects of captopril by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.carbamazepineMonitor Closely (1)carbamazepine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentcarvedilolSerious - Use Alternative (1)carvedilol will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededcenobamateMonitor Closely (1)cenobamate will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.ceritinibMonitor Closely (1)ceritinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cigarette smokingMonitor Closely (1)cigarette smoking will decrease the level or effect of riociguat by increasing metabolism. Modify Therapy/Monitor Closely. Consider titrating riociguat to dosage >2.5 mg PO TID if tolerated; may need to decrease dose if quit smokingcilostazolMonitor Closely (1)riociguat, cilostazol. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Riociguat is contraindicated with specific PDE-5 inhibitors (eg sildenafil, tadalafil, vardenafil) and nonspecific PDE-5 inhibitors (eg theophylline, dipyridamole) due to risk of hypotension; data are limited with other PDE inhibitors (eg, milrinone, cilostazol, roflumilast).citric acid/sodium bicarbonateMonitor Closely (1)citric acid/sodium bicarbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.clarithromycinMonitor Closely (1)clarithromycin will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cobicistatSerious - Use Alternative (1)cobicistat will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.conivaptanSerious - Use Alternative (2)conivaptan will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. conivaptan will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededcyclophosphamideMinor (1)cyclophosphamide will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclosporineSerious - Use Alternative (2)cyclosporine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (BCRP/ABCG2 substrate) with BCRP/ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed. cyclosporine will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededdabrafenibMonitor Closely (1)dabrafenib will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentSerious - Use Alternative (1)dabrafenib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededdarolutamideSerious - Use Alternative (1)darolutamide will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).darunavirSerious - Use Alternative (3)darunavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. darunavir will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed darunavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededdexamethasoneMonitor Closely (1)dexamethasone will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentdiltiazemMonitor Closely (1)riociguat, diltiazem. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Monitor patients closely for additive hypotensive effects if two or more of these agents are combined.dipyridamoleContraindicated (1)dipyridamole, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nonspecific PDE-5 inhibitors (eg, dipyridamole, theophylline) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.Serious - Use Alternative (2)dipyridamole will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed dipyridamole will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededdronedaroneSerious - Use Alternative (1)dronedarone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededefavirenzMonitor Closely (1)efavirenz will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentelagolixMonitor Closely (2)elagolix will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. elagolix decreases levels of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.eliglustatMonitor Closely (1)eliglustat increases levels of riociguat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.eltrombopagSerious - Use Alternative (1)eltrombopag will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededeluxadolineMonitor Closely (1)eluxadoline increases levels of riociguat by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.elvitegravir/cobicistat/emtricitabine/tenofovir DFSerious - Use Alternative (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if neededencorafenibMonitor Closely (2)encorafenib, riociguat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents. encorafenib will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.enzalutamideMonitor Closely (1)enzalutamide will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmenterdafitinibSerious -