enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. sparsentan will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. Serious - Use Alternative (1)phenytoin will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.piroxicamMonitor Closely (1)piroxicam and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs. posaconazoleSerious - Use Alternative (1)posaconazole, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .potassium acid phosphateMonitor Closely (1)sparsentan and potassium acid phosphate both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.potassium chlorideMonitor Closely (1)sparsentan and potassium chloride both increase serotonin levels. Use Caution/Monitor. Monitor serum potassium frequently.potassium citrateMonitor Closely (1)sparsentan and potassium citrate both increase serotonin levels. Use Caution/Monitor. Monitor serum potassium frequently.primidoneSerious - Use Alternative (1)primidone will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.progesterone intravaginal gelMonitor Closely (1)sparsentan will decrease the level or effect of progesterone intravaginal gel by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. progesterone micronizedMonitor Closely (1)sparsentan will decrease the level or effect of progesterone micronized by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. promethazineMonitor Closely (1)sparsentan will decrease the level or effect of promethazine by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.propofolMonitor Closely (2)sparsentan will decrease the level or effect of propofol by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates. sparsentan will decrease the level or effect of propofol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. quinupristin/dalfopristinMonitor Closely (1)quinupristin/dalfopristin will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. rabeprazoleMonitor Closely (1)sparsentan will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. Serious - Use Alternative (1)rabeprazole decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Proton pump inhibitors may decrease sparsentan exposure which may reduce efficacy of sparsentan.ranitidineSerious - Use Alternative (1)ranitidine decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. H2-antagonists may decrease sparsentan exposure which may reduce efficacy of sparsentan.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. rifampinMonitor Closely (1)sparsentan will decrease the level or effect of rifampin by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.Serious - Use Alternative (1)rifampin will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ritonavirSerious - Use Alternative (1)ritonavir, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .rucaparibSerious - Use Alternative (1)rucaparib, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .sacubitril/valsartanContraindicated (1)sparsentan, sacubitril/valsartan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of ARBs with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).salsalateMonitor Closely (1)salsalate and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs. saquinavirSerious - Use Alternative (1)saquinavir, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .schisandraMonitor Closely (1)schisandra will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. selegilineMonitor Closely (1)sparsentan will decrease the level or effect of selegiline by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.sertralineMonitor Closely (2)sertraline will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. sparsentan will decrease the level or effect of sertraline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. siponimodMonitor Closely (1)sparsentan will decrease the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. spironolactoneMonitor Closely (1)sparsentan and spironolactone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.St John's WortSerious - Use Alternative (1)St John's Wort will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.stiripentolSerious - Use Alternative (1)stiripentol, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .sulfadiazineMonitor Closely (1)sparsentan will decrease the level or effect of sulfadiazine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. sulfisoxazoleMonitor Closely (1)sparsentan will decrease the level or effect of sulfisoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. sulindacMonitor Closely (1)sulindac and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs. tamoxifenMonitor Closely (1)sparsentan will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. telmisartanContraindicated (1)sparsentan, telmisartan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of ARBs with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).tetracyclineMonitor Closely (1)tetracycline will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. tofacitinibMonitor Closely (1)sparsentan will decrease the level or effect of tofacitinib by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. tolbutamideMonitor Closely (1)sparsentan will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. tolmetinMonitor Closely (1)tolmetin and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs. topotecanSerious - Use Alternative (1)sparsentan will increase the level or effect of topotecan by Other (see comment). Avoid or Use Alternate Drug. Sparsentan (a BCRP inhibitor) may increase exposure of sensitive BCRP substrates and the risk of these substrates toxicities. torsemideMonitor Closely (1)sparsentan will decrease the level or effect of torsemide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. triamtereneMonitor Closely (1)sparsentan and triamterene both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.trimethoprimMonitor Closely (1)sparsentan will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. trimipramineMonitor Closely (1)sparsentan will decrease the level or effect of trimipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. tucatinibSerious - Use Alternative (1)tucatinib, sparsentan. Either increases levels of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .valsartanContraindicated (1)sparsentan, valsartan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of ARBs with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).velpatasvirMonitor Closely (1)sparsentan will decrease the level or effect of velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.verapamilMonitor Closely (1)verapamil will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. voriconazoleMonitor Closely (2)sparsentan will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. sparsentan will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. Serious - Use Alternative (1)voriconazole, sparsentan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration. .voxelotorMonitor Closely (1)voxelotor will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors. warfarinMonitor Closely (1)sparsentan will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. zafirlukastMonitor Closely (1)sparsentan will decrease the level or effect of zafirlukast by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates. >10% Peripheral edema (14%) Hypotension, including orthostatic hypotension (14%) Dizziness (13%) Hyperkalemia (13%) 1-10% Anemia (5%) Acute kidney injury (4%) Transaminase elevations (2.5%) Black Box Warnings Owing to risks of hepatotoxicity and birth defects, sparsentan is available only through a restricted program called the FILSPARI REMS Prescribers, patients, and pharmacies must enroll in the Risk Evaluation and Mitigation Strategies (REMS) program Hepatotoxicity Some endothelin receptor antagonists (ERAs) have caused elevations of aminotransferases (ALT, AST), hepatotoxicity, and liver failure In clinical studies, elevations of ALT or AST of ≥3x ULN observed in up to 2.5% of treated patients, including cases confirmed with rechallenge Measure transaminases and bilirubin before initiating and monthly for first 12 months of treatment, and then every 3 months