Sparsentan: uses, dosing, side effects & brands

Clinically significant adverse reactions that appear in other sections of the label include: • Hepatotoxicity [see Warnings and Precautions ( 5.1 )] • Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.3 )] • Hypotension [see Warnings and Precautions ( 5.4 )] • Acute Kidney Injury [see Warnings and Precautions ( 5.5 )] • Hyperkalemia [see Warnings and Precautions ( 5.6 )] • Fluid Retention [see Warnings and Precautions ( 5.7 )] Most common adverse reactions in patients with IgAN (≥5%) are hyperkalemia, hypotension (including orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney injury ( 6.1 ). Most common adverse reactions in patients with FSGS (≥5%) are peripheral edema, hypotension (including orthostatic hypotension), hyperkalemia, dizziness, and anemia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Travere Therapeutics at 1-877-659-5518 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. IgAN The safety of FILSPARI was evaluated in PROTECT ( NCT03762850 ), a randomized, double-blind, active-controlled clinical study in adults with IgAN. The data…

Use of FILSPARI is contraindicated in patients who are pregnant [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 )] . Do not co-administer FILSPARI with ARBs, ERAs, or aliskiren [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1 )]. • Pregnancy ( 4 ). • Concomitant use with angiotensin receptor blockers (ARBs), ERAs, or aliskiren ( 4 ).

Strong CYP3A inhibitors: Avoid concomitant use. Increased sparsentan exposure ( 2.7 , 7.2 , 12.3 ). • Moderate CYP3A inhibitors: Monitor adverse reactions. Increased sparsentan exposure ( 7.2 , 12.3 ). • Strong CYP3A inducers: Avoid concomitant use. Decreased sparsentan exposure ( 7.3 , 12.3 ). • Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase (COX-2) inhibitors: Monitor for signs of worsening renal function. Increased risk of kidney injury ( 7.4 ). • CYP2B6, 2C9, and 2C19 substrates: Monitor for substrate efficacy. Decreased exposure of these substrates ( 7.5 , 12.3 ). • P-gp substrates: Monitor for adverse reactions of P-gp substrates with narrow therapeutic indices. Increased exposure to substrates ( 7.6 , 12.3 ). • Agents Increasing Serum Potassium: Increased risk of hyperkalemia, monitor serum potassium frequently ( 5.6 , 7.7 ). 7.1 Renin-Angiotensin System Inhibitors and ERAs Do not coadminister FILSPARI with ARBs, ERAs, or aliskiren [see Dosage and Administration ( 2.1 ), Contraindications ( 4 )] . Combined use of these agents is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure). 7.2 Strong and Moderate CYP3A Inhibitors Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. If a strong CYP3A inhibitor cannot be avoided, interrupt treatment with FILSPARI. When resuming treatment with FILSPARI, consider dose titration [see Dosage and Administration ( 2.4 , 2.7 ), Clinical Pharmacology ( 12.3 )] . Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors [see Warnings and Precautions ( 5.4 , 5.5 , 5.6 , 5.7 )] . No FILSPARI dose adjustment is needed. Sparsentan is a CYP3A substrate. Concomitant use with a strong CYP3A inhibitor increases sparsentan C max and AUC [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of FILSPARI adverse reactions. 7.3 Strong CYP3A Inducers Avoid concomitant use with a strong CYP3A inducer. Sparsentan is a CYP3A substrate. Concomitant use with a strong CYP3A inducer decreases sparsentan C max and AUC [see Clinical Pharmacology ( 12.3 )] , which may reduce FILSPARI efficacy. 7.4 Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including 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 [see Warnings and Precautions ( 5.5 )] . These effects are usually reversible. 7.5 CYP2B6, 2C9, and 2C19 Substrates Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. Sparsentan is a weak inducer of CYP2B6 and 2C9, and a moderate inducer of 2C19. Sparsentan decreases exposure of these substrates [see Clinical Pharmacology ( 12.3 )] , which may reduce efficacy related to these substrates. 7.6 P-gp Substrates Monitor for adverse reactions and consider dose reduction of P-gp substrates with narrow therapeutic indices when co-administered with FILSPARI. FILSPARI is a weak P-gp inhibitor. Co-administration of FILSPARI may increase plasma concentrations of P-gp substrate drugs [see Clinical Pharmacology ( 12.3 )] . 7.7 Agents Increasing Serum Potassium Monitor serum potassium frequently in patients treated with FILSPARI and other agents that increase serum potassium. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia [see Warnings and Precautions ( 5.6 )] .