sparsentan (Rx)

Brand and Other Names:Filspari

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 200mg
  • 400mg

IgA Nephropathy

Indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN; also known as Berger disease) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g

200 mg PO qDay initially; after 14 days, increase to recommended dose of 400 mg qDay, as tolerated

When resuming treatment after an interruption, consider starting at 200 mg/day, then after 14 days, increase to 400 mg/day

Dosage Modifications

ALT/AST >3x to ≤8x ULN

  • Confirm elevation with repeat measure
  • If confirmed, interrupt treatment, and monitor ALT/AST levels and bilirubin at least weekly, and INR as needed, until levels return to pretreatment values and the patient is asymptomatic
  • Do not resume treatment if any of the following occurs without other cause found
    • ALT/AST >3x ULN and total bilirubin >2x ULN or INR >1.5
    • ALT/AST >3x ULN, with symptoms of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5% eosinophils)
    • ALT/AST >5x ULN for >2 weeks
  • If treatment resumed, initiate at 200 mg qDay, with reassessment of hepatic enzyme levels and bilirubin within 3 days; close monitoring required in these patients

ALT/AST >8 x ULN

  • Permanently discontinue if no other cause found

Coadministration of strong CYP3A4 inhibitors

  • Avoid coadministration
  • If use is unavoidable, interrupt sparsentan

Renal impairment

  • Mild-to-moderate (eGFR 30-89 mL/min/1.73 m2): No clinically significant differences in pharmacokinetics observed
  • Severe (eGFR <30 mL/min/1.73 m2): Not studied

Hepatic impairment

  • Mild, moderate, or severe (Child-Pugh A-C): Avoid use with any hepatic impairment because of risk of serious liver injury

Dosing Considerations

Before initiating

  • Verify females of reproductive potential are not pregnant and are using effect contraception
  • Measure ALT, AST, and bilirubin; avoid initiating if >3x ULN
  • Discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors, endothelin receptor antagonists (ERAs), and aliskiren

Monitoring

  • Monitor ALT, AST, and bilirubin before initiating, monthly for first 12 months, and then every 3 months during treatment
  • Verify females of reproductive potential are not pregnant monthly during treatment and 1 month after discontinuing drug

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and sparsentan

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (14)

            • aliskiren

              sparsentan, aliskiren. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of aliskiren with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

            • ambrisentan

              sparsentan, ambrisentan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

            • aprocitentan

              sparsentan, aprocitentan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

            • azilsartan

              sparsentan, azilsartan. 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).

            • bosentan

              sparsentan, bosentan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

            • candesartan

              sparsentan, candesartan. 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).

            • eprosartan

              sparsentan, eprosartan. 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).

            • irbesartan

              sparsentan, irbesartan. 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).

            • losartan

              sparsentan, losartan. 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).

            • macitentan

              sparsentan, macitentan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

            • olmesartan

              sparsentan, olmesartan. 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).

            • sacubitril/valsartan

              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).

            • telmisartan

              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).

            • valsartan

              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).

            Serious - Use Alternative (51)

            • apalutamide

              apalutamide will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • atazanavir

              atazanavir will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

            • carbamazepine

              carbamazepine will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

            • cimetidine

              cimetidine 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.

            • clarithromycin

              clarithromycin will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

            • cobicistat

              cobicistat will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

            • conivaptan

              conivaptan, 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. .

            • darunavir

              darunavir, 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. .

            • dexlansoprazole

              dexlansoprazole 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.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

            • enzalutamide

              enzalutamide will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • esomeprazole

              esomeprazole 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.

            • famotidine

              famotidine 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.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • grapefruit

              grapefruit, 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. .

            • idelalisib

              idelalisib, 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. .

            • indinavir

              indinavir, 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. .

            • irinotecan

              sparsentan will increase the level or effect of irinotecan 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.

            • itraconazole

              itraconazole, 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. .

            • ketoconazole

              ketoconazole, 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. .

            • lansoprazole

              lansoprazole 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.

            • levoketoconazole

              levoketoconazole, 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. .

            • lonafarnib

              lonafarnib, 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. .

            • lopinavir

              lopinavir, 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. .

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • methotrexate

              sparsentan will increase the level or effect of methotrexate 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.

            • mifepristone

              mifepristone, 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. .

            • mitotane

              mitotane will decrease the level or effect of sparsentan by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.

              mitotane will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone, 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. .

            • nelfinavir

              nelfinavir, 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. .

            • nirmatrelvir/ritonavir

              nirmatrelvir/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. .

            • nizatidine

              nizatidine 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.

            • omeprazole

              omeprazole 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.

            • pantoprazole

              pantoprazole 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.

            • phenobarbital

              phenobarbital will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenytoin

              phenytoin will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • posaconazole

              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. .

            • primidone

              primidone will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rabeprazole

              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.

            • ranitidine

              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.

            • repotrectinib

              sparsentan will increase the level or effect of repotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ritonavir

              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. .

            • rucaparib

              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. .

            • saquinavir

              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. .

            • St John's Wort

              St John's Wort will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • stiripentol

              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. .

            • topotecan

              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.

            • tucatinib

              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. .

            • voriconazole

              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. .

            Monitor Closely (154)

            • adagrasib

              adagrasib 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.

            • aluminum hydroxide

              aluminum hydroxide decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer sparsentan 2 hours before or after administration of antacids. Antacids may decrease sparsentan exposure which may reduce efficacy of sparsentan.

            • amiloride

              sparsentan and amiloride both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

            • amiodarone

              amiodarone 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 amiodarone 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.

            • aprepitant

              aprepitant 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.

            • aspirin

              aspirin 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.

            • aspirin rectal

              aspirin rectal 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.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer sparsentan 2 hours before or after administration of antacids. Antacids may decrease sparsentan exposure which may reduce efficacy of sparsentan.

            • avapritinib

              sparsentan will decrease the level or effect of avapritinib 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.

            • avatrombopag

              sparsentan will decrease the level or effect of avatrombopag 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.

            • belzutifan

              sparsentan will decrease the level or effect of belzutifan 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.

            • bicalutamide

              bicalutamide 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.

            • bortezomib

              sparsentan will decrease the level or effect of bortezomib 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.

            • brivaracetam

              sparsentan will decrease the level or effect of brivaracetam 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.

            • bupropion

              sparsentan will decrease the level or effect of bupropion 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.

            • calcium carbonate

              calcium carbonate decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer sparsentan 2 hours before or after administration of antacids. Antacids may decrease sparsentan exposure which may reduce efficacy of sparsentan.

            • cannabidiol

              sparsentan will decrease the level or effect of cannabidiol 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.

            • carisoprodol

              sparsentan will decrease the level or effect of carisoprodol 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.

            • carvedilol

              sparsentan will decrease the level or effect of carvedilol 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.

            • celecoxib

              celecoxib 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.

              sparsentan will decrease the level or effect of celecoxib 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.

            • ceritinib

              ceritinib 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.

            • chlorpropamide

              sparsentan will decrease the level or effect of chlorpropamide 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.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate 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.

            • citalopram

              sparsentan will decrease the level or effect of citalopram 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.

            • clobazam

              sparsentan will decrease the level or effect of clobazam 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.

            • clomipramine

              sparsentan will decrease the level or effect of clomipramine 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.

            • clotrimazole

              clotrimazole will increase the level or effect of sparsentan by affecting hepatic enzyme CYP2E1 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.

            • crizotinib

              crizotinib 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.

            • cyclophosphamide

              sparsentan will decrease the level or effect of cyclophosphamide 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.

            • cyclosporine

              cyclosporine 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.

            • dapsone

              sparsentan will decrease the level or effect of dapsone 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.

            • desogestrel

              sparsentan will decrease the level or effect of desogestrel 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.

            • dexlansoprazole

              sparsentan will decrease the level or effect of dexlansoprazole 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.

            • diazepam

              sparsentan will decrease the level or effect of diazepam 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.

            • diazepam intranasal

              sparsentan will decrease the level or effect of diazepam intranasal 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.

            • diclofenac

              diclofenac 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.

              sparsentan will decrease the level or effect of diclofenac 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.

            • diflunisal

              diflunisal 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.

            • diltiazem

              diltiazem 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.

            • doxycycline

              doxycycline 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.

            • dronabinol

              sparsentan will decrease the level or effect of dronabinol 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.

            • dronedarone

              dronedarone 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.

            • drospirenone

              sparsentan and drospirenone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

            • efavirenz

              sparsentan will decrease the level or effect of efavirenz 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.

            • encorafenib

              encorafenib 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.

            • entacapone

              entacapone 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.

            • erdafitinib

              sparsentan will decrease the level or effect of erdafitinib 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.

            • erythromycin base

              erythromycin base 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.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate 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.

            • erythromycin lactobionate

              erythromycin lactobionate 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.

            • erythromycin stearate

              erythromycin stearate 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.

            • escitalopram

              sparsentan will decrease the level or effect of escitalopram 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.

            • esomeprazole

              sparsentan will decrease the level or effect of esomeprazole 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.

            • etodolac

              etodolac 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.

            • etravirine

              sparsentan will decrease the level or effect of etravirine 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 etravirine 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.

            • fedratinib

              fedratinib 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.

            • fenoprofen

              fenoprofen 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.

            • fexinidazole

              fexinidazole 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.

            • flibanserin

              sparsentan will decrease the level or effect of flibanserin 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.

            • fluconazole

              fluconazole 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.

            • fluoxetine

              sparsentan will decrease the level or effect of fluoxetine 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.

            • flurbiprofen

              flurbiprofen 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.

            • fluvastatin

              sparsentan will decrease the level or effect of fluvastatin 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.

            • fluvoxamine

              fluvoxamine 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.

            • fosamprenavir

              fosamprenavir 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.

            • fosphenytoin

              sparsentan will decrease the level or effect of fosphenytoin 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 fosphenytoin 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.

            • fospropofol

              sparsentan will decrease the level or effect of fospropofol 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.

            • fostamatinib

              fostamatinib 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.

            • glimepiride

              sparsentan will decrease the level or effect of glimepiride 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.

            • glipizide

              sparsentan will decrease the level or effect of glipizide 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.

            • glyburide

              sparsentan will decrease the level or effect of glyburide 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.

            • haloperidol

              haloperidol 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.

            • ibrexafungerp

              ibrexafungerp 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.

            • ibuprofen

              ibuprofen 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.

            • ibuprofen IV

              ibuprofen IV 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.

            • ibuprofen/famotidine

              ibuprofen/famotidine 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.

            • ifosfamide

              sparsentan will decrease the level or effect of ifosfamide 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.

            • iloperidone

              iloperidone 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.

            • imatinib

              sparsentan will decrease the level or effect of imatinib 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.

            • imipramine

              sparsentan will decrease the level or effect of imipramine 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.

            • indomethacin

              indomethacin 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.

            • irinotecan

              sparsentan will decrease the level or effect of irinotecan 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.

            • ketamine

              sparsentan will decrease the level or effect of ketamine 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 ketamine 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.

            • ketoprofen

              ketoprofen 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.

            • ketorolac

              ketorolac 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.

            • ketorolac intranasal

              ketorolac intranasal 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.

            • lacosamide

              sparsentan will decrease the level or effect of lacosamide 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.

            • lansoprazole

              sparsentan will decrease the level or effect of lansoprazole 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.

            • larotrectinib

              larotrectinib 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.

            • lenacapavir

              lenacapavir 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.

            • lesinurad

              sparsentan will decrease the level or effect of lesinurad 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.

            • letermovir

              letermovir 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.

            • lonafarnib

              sparsentan will decrease the level or effect of lonafarnib 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.

            • losartan

              sparsentan will decrease the level or effect of losartan 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.

            • magaldrate

              magaldrate decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer sparsentan 2 hours before or after administration of antacids. Antacids may decrease sparsentan exposure which may reduce efficacy of sparsentan.

            • magnesium oxide

              magnesium oxide decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer sparsentan 2 hours before or after administration of antacids. Antacids may decrease sparsentan exposure which may reduce efficacy of sparsentan.

            • mavacamten

              sparsentan will decrease the level or effect of mavacamten 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.

            • meclofenamate

              meclofenamate 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.

            • mefenamic acid

              mefenamic acid 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.

            • meloxicam

              meloxicam 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.

            • mephobarbital

              sparsentan will decrease the level or effect of mephobarbital 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.

            • methohexital

              sparsentan will decrease the level or effect of methohexital 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.

            • methsuximide

              sparsentan will decrease the level or effect of methsuximide 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.

            • metronidazole

              metronidazole 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.

            • miconazole oral

              sparsentan will decrease the level or effect of miconazole oral 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.

            • modafinil

              sparsentan will decrease the level or effect of modafinil 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.

            • montelukast

              sparsentan will decrease the level or effect of montelukast 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.

            • nabumetone

              nabumetone 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.

            • naproxen

              naproxen 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.

            • nateglinide

              sparsentan will decrease the level or effect of nateglinide 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.

            • nelfinavir

              sparsentan will decrease the level or effect of nelfinavir 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.

            • netupitant/palonosetron

              netupitant/palonosetron 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.

            • omeprazole

              sparsentan will decrease the level or effect of omeprazole 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.

            • ospemifene

              sparsentan will decrease the level or effect of ospemifene 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 ospemifene 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.

            • oxaprozin

              oxaprozin 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.

            • pantoprazole

              sparsentan will decrease the level or effect of pantoprazole 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.

            • pentamidine

              sparsentan will increase the level or effect of pentamidine 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.

            • phenobarbital

              sparsentan will increase the level or effect of phenobarbital 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.

            • phenytoin

              sparsentan will decrease the level or effect of phenytoin 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 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.

            • piroxicam

              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.

            • potassium acid phosphate

              sparsentan and potassium acid phosphate both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

            • potassium chloride

              sparsentan and potassium chloride both increase serotonin levels. Use Caution/Monitor. Monitor serum potassium frequently.

            • potassium citrate

              sparsentan and potassium citrate both increase serotonin levels. Use Caution/Monitor. Monitor serum potassium frequently.

            • progesterone intravaginal gel

              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 micronized

              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.

            • promethazine

              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.

            • propofol

              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/dalfopristin

              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.

            • rabeprazole

              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.

            • ribociclib

              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.

            • rifampin

              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.

            • salsalate

              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.

            • schisandra

              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.

            • selegiline

              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.

            • sertraline

              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.

            • siponimod

              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.

            • spironolactone

              sparsentan and spironolactone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

            • sulfadiazine

              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.

            • sulfisoxazole

              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.

            • sulindac

              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.

            • tamoxifen

              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.

            • tetracycline

              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.

            • tofacitinib

              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.

            • tolbutamide

              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.

            • tolmetin

              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.

            • torsemide

              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.

            • triamterene

              sparsentan and triamterene both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.

            • trimethoprim

              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.

            • trimipramine

              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.

            • velpatasvir

              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.

            • verapamil

              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.

            • voriconazole

              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.

            • voxelotor

              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.

            • warfarin

              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.

            • zafirlukast

              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.

            Minor (0)

              Previous
              Next:

              Adverse Effects

              >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%)

              Previous
              Next:

              Warnings

              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 during treatment
              • Interrupt treatment and closely monitor if aminotransferase elevations >3x ULN
              • Avoid use in patients with elevated aminotransferases at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity

              Embryofetal toxicity

              • Can cause major birth defects if used by pregnant patients, based on animal data
              • Pregnancy testing is required before initiating treatment, during treatment, and 1 month after discontinuation
              • Patients who can become pregnant must use effective contraception before the initiation of treatment, during treatment, and for 1 month after discontinuation

              Contraindications

              Pregnant patients

              Administration with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren

              Cautions

              Based on animal data, can cause fetal harm when administered to pregnant females and is contraindicated during pregnancy

              Monitor serum potassium periodically and treat appropriately; dosage reduction or discontinuation of sparsentan may be required

              Fluid retention may occur with ERAs; if clinically significant fluid retention develops, evaluate to determine the cause and the potential need to initiate or modify diuretic dose, then consider modifying sparsentan dose

              Kidney injury

              • Monitor kidney function periodically
              • Drugs that inhibit the renin-angiotensin system (RAS) can cause acute kidney injury
              • Caution in patients whose kidney function may depend in part on activity of RAS (eg, renal artery stenosis, chronic kidney disease, severe CHF, volume depletion)
              • Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function

              Hypotension

              • Hypotension observed in clinical trials
              • In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status
              • If hypotension develops despite elimination or reduction of other antihypertensive medications, consider dose reduction or dose interruption
              • Transient hypotensive response is not a contraindication to further dosing, which can be given once blood pressure has stabilized

              Hepatotoxicity

              • Some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure
              • Elevated ALT/AST ≥3x ULN observed in treated patients, including cases confirmed with rechallenge
              • Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment and seek medical attention
              • If aminotransferase levels are abnormal at any time during treatment, interrupt dosing and monitor as recommended

              Requirements of the FILSPARI REMS

              • Prescribers must be certified with the FILSPARI REMS by enrolling andcompleting training
              • All patients must enroll in the FILSPARI REMS before initiating treatment andcomply with monitoring requirements
              • Pharmacies must be certified with the FILSPARI REMS and must dispense only to patients who are authorized to receive therapy
              • Additional information available at https://rems.filspari.com/ or 1-833-513-1325

              Drug interaction overview

              • Substrate of CYP3A (major)
              • Inducer of CYP2B6, CYP2C9, CYP2C19
              • Inhibitor of P-gp and BCRP
              • RAS inhibitors and ERAs
                • Contraindicated
                • Coadministration with RAS inhibitors, ERAs, or aliskiren is contraindicated owing to additive pharmacologic effects
              • Strong CYP3A inhibitors
                • Avoid coadministration
                • Strong CYP3A inhibitors increases sparsentan peak plasma levels and AUC, which may increase adverse effects
                • If use is unavoidable, interrupt treatment with sparsentan
                • When resuming sparsentan, consider dose titration
              • Moderate CYP3A inhibitors
                • Monitor
                • No dosage adjustment needed; monitor blood pressure, serum potassium, edema, and kidney function regularly if coadministered
              • Strong CYP3A inducers
                • Avoid
                • Strong CYP3A inducers decrease sparsentan peak plasma levels and AUC, which may decrease efficacy
              • Antacids
                • Modify dosage schedule
                • Sparsentan exhibits pH-dependent solubility
                • Administer sparsentan 2 hr before or after administration of antacids
                • Coadministration may decrease sparsentan exposure, which may reduce efficacy
              • Acid-reducing agents
                • Avoid
                • Sparsentan exhibits pH-dependent solubility
                • Coadministration with acid-reducing agents (eg, histamine H2 receptor antagonist, proton pump inhibitor [PPI]) may decrease sparsentan exposure, which may reduce efficacy
              • NSAIDs (including COX-2 inhibitors)
                • Monitor for signs of worsening renal function
                • In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, coadministration of NSAIDs and selective COX-2 inhibitors with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure
              • CYP2B6, 2C9, and 2C19 substrates
                • Monitor for efficacy of substrate
                • Consider dosage adjustment in accordance with the substrate’s prescribing information
              • P-gp and BCRP substrates
                • Avoid with sensitive P-gp and BCRP substrates
                • Sparsentan is an inhibitor of P-gp and BCRP
              • Agents increasing serum potassium
                • Monitor serum potassium frequently
                • Coadministration with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia
              Previous
              Next:

              Pregnancy & Lactation

              Pregnancy

              Contraindicated in pregnant patients

              Based on animal data, can cause fetal harm, including birth defects and fetal death, when administered to pregnant females

              Verify patients of reproductive potential are not pregnant before initiating, monthly during treatment, and 1 month after discontinuing drug

              Advise pregnant patients of the potential risk to the fetus

              Animal studies

              • Oral administration to pregnant rats throughout organogenesis at 10 times the maximum recommended human dose in mg/day caused teratogenic effects in rats, including craniofacial malformations, skeletal abnormalities, increased embryo-fetal lethality, and reduced fetal weights

              Contraception

              • Patients of reproductive potential: Use an effective method of contraception before initiating, during treatment, and for 1 month after discontinuing

              Lactation

              Data are not available on presence of drug in human milk, effects on breastfed infants, or effect on milk production

              Owing to the potential for adverse reactions, such as hypotension in breastfed infants, advise patients not to breastfeed during treatment

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

              Previous
              Next:

              Pharmacology

              Mechanism of Action

              Dual endothelin angiotensin receptor antagonist (DEARA)

              Selectively blocks endothelin 1A receptors (ETAR) and angiotensin II type 1 receptors (AT1R)

              Endothelin-1 and angiotensin II are thought to contribute to the pathogenesis of immunoglobulin A nephropathy (IgAN) via the ETAR and AT1R, respectively

              Absorption

              Peak plasma time: ~3 hr

              Peak plasma concentration, steady-state: 6.47 mcg/mL

              AUC, steady-state: 63.6 mcg⋅hr/mL

              Distribution

              Protein bound: >99%

              Vd: 61.4 L

              Metabolism

              CYP3A is major metabolic pathway

              Elimination

              Half-life: 9.6 hr

              Clearance: 5.11 L/hr

              Excretion: Feces 80% (9% unchanged); urine 2% (negligible amount unchanged)

              Previous
              Next:

              Administration

              Oral Administration

              Swallow tablets whole with water before morning or evening meal

              Maintain same dosing pattern in relationship to meals

              Missed dose

              • Take next dose at regularly scheduled time
              • Do not take double or extra doses

              Storage

              Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

              Store in its original container

              Previous
              Next:

              Images

              No images available for this drug.
              Previous
              Next:

              Patient Handout

              A Patient Handout is not currently available for this monograph.
              Previous
              Next:

              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
              Additional Offers
              Email to Patient

              From:

              To:

              The recipient will receive more details and instructions to access this offer.

              By clicking send, you acknowledge that you have permission to email the recipient with this information.

              Email Forms to Patient

              From:

              To:

              The recipient will receive more details and instructions to access this offer.

              By clicking send, you acknowledge that you have permission to email the recipient with this information.

              Previous
              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.