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Do not coadminister sparsentan with ARBs, ERAs, or aliskiren.
Combined use of these agents is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure).
Avoid concomitant use of sparsentan with strong CYP3A inhibitors. If a strong CYP3A inhibitor cannot be avoided, interrupt treatment with sparsentan. When resuming treatment with sparsentan, consider dose titration.
Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors. No sparsentan dose adjustment is needed.
Sparsentan is a CYP3A substrate. Concomitant use with a strong CYP3A inhibitor increases sparsentan Cmax and AUC, which may increase the risk of sparsentan adverse reactions.
Avoid concomitant use with a strong CYP3A inducer. Sparsentan is a CYP3A substrate. Concomitant use with a strong CYP3A inducer decreases sparsentan Cmax and AUC, which may reduce sparsentan efficacy.
Administer sparsentan 2 hours before or after administration of antacids. Avoid concomitant use of acid reducing agents (histamine H2 receptor antagonist and PPI proton pump inhibitor) with sparsentan. Sparsentan exhibits pH-dependent solubility. Antacids or acid reducing agents may decrease sparsentan exposure which may reduce sparsentan efficacy.
Selective Cyclooxygenase-2 (COX-2) Inhibitors Monitor for signs of worsening renal function with concomitant use with NSAIDs (including selective COX-2 inhibitors). In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, concomitant use of NSAIDs (including selective COX-2 inhibitors) with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure. These effects are usually reversible.
Monitor for efficacy of the concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. Sparsentan is an inducer of CYP2B6, 2C9, and 2C19. Sparsentan decreases exposure of these substrates, which may reduce efficacy related to these substrates.
Avoid concomitant use of sensitive substrates of P-gp and BCRP with sparsentan. Sparsentan is an inhibitor of P-gp and BCRP. Sparsentan may increase exposure of these transporter substrates, which may increase the risk of adverse reactions related to these substrates.
Monitor serum potassium frequently in patients treated with sparsentan and other agents that increase serum potassium. Concomitant use of sparsentan with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia.
from FDA，2023.02
