SPARSENTAN TAB
Clinical Criteria Summary
Indication
- FDA approved to reduce proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g.
- Approved under accelerated approval based on reduction of proteinuria; it has not been established whether sparsentan slows kidney function decline. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
Dosing & Administration
- Available as 200 mg and 400 mg tablets.
- Administered once daily, swallowed whole with water prior to the morning or evening meal.
- Initial dosing is 200 mg orally once daily; after 14 days, increase to 400 mg once daily as tolerated.
REMS Requirements
- Use is restricted to the FILSPARI Risk Evaluation and Mitigation Strategy (REMS) Program.
- Prescribers must be certified by enrolling and completing training.
- All patients must enroll prior to initiating treatment and comply with monitoring requirements.
- Pharmacies must be certified and dispense only to patients authorized to receive sparsentan.
Contraindications
- Pregnancy.
- Concomitant use of angiotensin II receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren.
Monitoring & Safety Precautions
- Hepatotoxicity: Measure transaminases and bilirubin before initiating treatment, monthly for the first 12 months, then every 3 months during treatment. Interrupt treatment if aminotransferase elevations exceed 3 times the upper limit of normal (ULN). Avoid initiation in patients with baseline aminotransferases >3x ULN due to increased risk and monitoring difficulty. Advise patients to immediately stop treatment and seek medical attention if symptoms of hepatotoxicity occur.
- Embryo-Fetal Toxicity: Require pregnancy testing before initiation, during treatment, and one month after discontinuation. Patients who can become pregnant must use effective contraception before, during, and for one month after treatment.
- Hypotension: Monitor patients at risk; consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. Consider dose reduction or interruption if hypotension develops despite adjustments. Transient hypotensive response is not a contraindication to further dosing once blood pressure stabilizes.
- Acute Kidney Injury: Periodically monitor kidney function. Withhold or discontinue therapy in patients who develop a clinically significant decrease in kidney function. Particular risk exists for patients whose kidney function depends on the renin-angiotensin system (e.g., renal artery stenosis, CKD, severe congestive heart failure, volume depletion).
- Hyperkalemia: Periodically monitor serum potassium and treat appropriately. Increased risk in patients with advanced kidney disease or those taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes). Consider dose reduction or discontinuation if hyperkalemia develops.
- Fluid Retention: Evaluate clinically significant fluid retention to determine cause and potential need for diuretic adjustment; consider modifying sparsentan dose. Not evaluated in patients with heart failure.
Drug Interactions & Use Restrictions
- RAS inhibitors, ERAs, aliskiren: Contraindicated due to increased risk of hypotension and hyperkalemia.
- Strong CYP3A inhibitors/inducers: Avoid concomitant use (increases or decreases sparsentan exposure, respectively).
- Moderate CYP3A inhibitors: Monitor for adverse reactions due to increased sparsentan exposure.
- Antacids/Acid-reducing agents: Avoid antacid use within 2 hours before or after sparsentan; avoid concomitant use of acid-reducing agents due to decreased sparsentan exposure.
- NSAIDs/COX-2 inhibitors: Monitor for signs of worsening renal function and increased risk of kidney injury.
- CYP2B6, 2C9, 2C19 substrates: Monitor for efficacy due to decreased substrate exposure.
- Sensitive P-gp and BCRP substrates: Avoid concomitant use due to increased substrate exposure.
- Agents increasing serum potassium: Monitor serum potassium frequently due to increased hyperkalemia risk.
Patient Selection/Clinical Context
- Target population includes patients with biopsy-proven primary IgAN, proteinuria > 1 g/day at screening, eGFR > 30 mL/min/1.73 m2 at screening, on a stable dose of an ACEI and/or ARB at maximum tolerated dose for ≥12 weeks prior to screening, and SBP < 150 mmHg and DBP < 100 mmHg.
- Excludes patients with secondary IgAN or IgA vasculitis; cellular glomerular crescents > 25% on renal biopsy; other CKD causes; history of organ transplantation (except corneal); systemic immunosuppressants use > 2 weeks in the last 3 months; heart failure history/hospitalization/unexplained dyspnea/edema; significant cerebrovascular or coronary artery disease within 6 months; jaundice/hepatitis/liver disease or ALT/AST > 2x ULN; malignancy (except adequately treated BCC/SCC/cervical cancer in past 2 years); hematocrit < 27% or hemoglobin < 9 g/dL; potassium > 5.5 mEq/L; alcohol/illicit drug use disorder; serious side effect/allergy to ARB/ERA; or pregnancy/breastfeeding/planning pregnancy.
- Place in therapy follows optimized supportive care (lifestyle intervention, dietary sodium restriction, smoking cessation, weight control, exercise) and ACEI/ARB treatment for proteinuria > 0.5 g/d. Glucocorticoid therapy may be considered for patients remaining at high risk of progressive CKD despite maximal supportive care.