require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed lopinavir 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 neededlorlatinibMonitor Closely (1)lorlatinib will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lovastatinSerious - Use Alternative (1)lovastatin 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 neededmagnesium hydroxideMonitor Closely (1)magnesium 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.magnesium oxideMonitor Closely (1)magnesium oxide 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.mefloquineSerious - Use Alternative (1)mefloquine 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 neededmifepristoneSerious - Use Alternative (1)mifepristone 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 neededmilrinoneMonitor Closely (1)milrinone, riociguat. Either increases effects 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.mitotaneMonitor Closely (1)mitotane decreases levels of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.nafcillinMonitor Closely (1)nafcillin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentnefazodoneMonitor Closely (1)nefazodone will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone 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 needednelfinavirSerious - Use Alternative (3)nelfinavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. nelfinavir 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 nelfinavir 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 needednevirapineMonitor Closely (1)nevirapine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentnicardipineSerious - Use Alternative (1)nicardipine 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 needednifedipineSerious - Use Alternative (1)nifedipine 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 needednilotinibSerious - Use Alternative (1)nilotinib 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 needednirmatrelvir/ritonavirMonitor Closely (1)nirmatrelvir/ritonavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Riociguat is metabolized by CYP3A4 and eliminated unchanged in the bile and renally. Consider temporary dose reduction of riociguat and monitor for signs and symptoms of hypotension. nitroglycerin IVContraindicated (1)nitroglycerin IV, 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.nitroglycerin POContraindicated (1)nitroglycerin PO, 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.nitroglycerin sublingualContraindicated (1)nitroglycerin sublingual, 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.nitroglycerin transdermalContraindicated (1)nitroglycerin transdermal, 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.nitroglycerin translingualContraindicated (1)nitroglycerin translingual, 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.omaveloxoloneMonitor Closely (1)omaveloxolone will decrease the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed. omeprazoleMonitor Closely (1)omeprazole will decrease the level or effect of riociguat by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.oteseconazoleMonitor Closely (1)oteseconazole will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.oxcarbazepineMonitor Closely (1)oxcarbazepine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentpaliperidoneSerious - Use Alternative (1)paliperidone 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 neededpantoprazoleSerious - Use Alternative (1)pantoprazole 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 neededpentobarbitalMonitor Closely (1)pentobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentphenobarbitalMonitor Closely (1)phenobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentphenytoinMonitor Closely (1)phenytoin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentponatinibSerious - Use Alternative (2)ponatinib 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 ponatinib 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 neededposaconazoleSerious - Use Alternative (2)posaconazole 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 posaconazole 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 neededprimidoneMonitor Closely (1)primidone will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentprogesterone micronizedSerious - Use Alternative (1)progesterone micronized 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 neededpropafenoneSerious - Use Alternative (1)propafenone 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 neededpropranololSerious - Use Alternative (1)propranolol 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 neededquinidineSerious - Use Alternative (2)quinidine 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 quinidine 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 neededquinineSerious - Use Alternative (1)quinine 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 neededranolazineSerious - Use Alternative (1)ranolazine 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 neededregorafenibMonitor Closely (1)regorafenib will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.ribociclibMinor (1)ribociclib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentrifampinMonitor Closely (1)rifampin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustmentrifapentineMonitor Closely (1)rifapentine will decrease the level or effect of riociguat