neededritonavirritonavir 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 neededritonavir 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 neededritonavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.saquinavirsaquinavir 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 neededsaquinavir 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 neededsaquinavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.simvastatinsimvastatin 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 neededsotorasibsotorasib will decrease the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.sunitinibsunitinib 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 neededsunitinib 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 neededtacrolimustacrolimus 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 neededtamoxifentamoxifen 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 neededtepotinibtepotinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.tipranavirtipranavir 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 neededtucatinibtucatinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.ulipristalulipristal 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 neededvandetanibvandetanib 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 neededvandetanib 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 neededvemurafenibvemurafenib 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 neededverapamilverapamil 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 neededvoriconazolevoriconazole 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 neededvoxelotorvoxelotor will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.Monitor Closely (81)abacavirabacavir will increase the level or effect of riociguat by unknown mechanism. Modify Therapy/Monitor Closely. Riociguat dose reduction may be necessaryacalabrutinibacalabrutinib increases levels of riociguat by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.aluminum hydroxidealuminum hydroxide 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.aluminum hydroxide/magnesium carbonatealuminum hydroxide/magnesium 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.aluminum hydroxide/magnesium trisilicatealuminum 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.apalutamideapalutamide 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.aspirin/citric acid/sodium bicarbonateaspirin/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.atazanaviratazanavir 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.benazeprilriociguat, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.berotralstatberotralstat 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.bosentanbosentan 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 carbonatecalcium 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.cannabidiolcannabidiol 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.captoprilriociguat increases effects of captopril by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.carbamazepinecarbamazepine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentcenobamatecenobamate 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.ceritinibceritinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cigarette smokingcigarette 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 smokingcilostazolriociguat, 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 bicarbonatecitric 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.clarithromycinclarithromycin will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.dabrafenibdabrafenib will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentdexamethasonedexamethasone will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentdiltiazemriociguat, 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.efavirenzefavirenz will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentelagolixelagolix 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.eliglustateliglustat 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.eluxadolineeluxadoline increases levels of riociguat by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.encorafenibencorafenib, 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.enzalutamideenzalutamide will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmenteslicarbazepine acetateeslicarbazepine acetate will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentesomeprazoleesomeprazole will decrease the level or effect of riociguat by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.etravirineetravirine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentfedratinibfedratinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.fosphenytoinfosphenytoin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentfostamatinibfostamatinib will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp/BCRP substrate drugs. Monitor for toxicities of P-gp/BCRP substrate drug that may