What are the precautions for using sparsentan?

Sparsentan is an endothelin and angiotensin II receptor antagonist indicated for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for rapid disease progression, typically with a urine protein/creatinine ratio (UPCR) ≥1.5 g/g. There are precautions when using sparsentan, as follows:

1. To reduce the risk of potentially serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin before starting sparsentan treatment and monthly for the first 12 months of treatment, and then every 3 months during treatment. Advise patients who develop symptoms suggestive of hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or pruritus) to immediately discontinue treatment with FILSPARI and seek medical attention. If transaminase levels are abnormal at any time during treatment, sparsentan treatment should be interrupted and monitored as recommended.

Patients with elevated transaminases (>3x ULN) should avoid initiating sparsentan therapy before initiating dosing as monitoring for hepatotoxicity may be more difficult in these patients and these patients may be at increased risk for severe hepatotoxicity.

2. According to data from animal reproduction studies, the use of sparsentan in pregnant patients may cause harm to the fetus, so it is contraindicated during pregnancy. Inform patients of childbearing potential of the potential risk to the fetus. Obtain pregnancy test results before starting treatment with sparsentan, monthly during treatment, and 1 month after stopping treatment. It is recommended that patients of childbearing potential use effective contraception before starting treatment, during treatment and for 1 month after stopping treatment.

3. For all patients, due to the risk of hepatotoxicity and embryo-fetal toxicity, FILSPARI is only available through a restricted program under REMS, called FILSPARI REMS. All patients must be enrolled in FILSPARI REMS and comply with monitoring requirements before starting treatment.

4. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. If hypotension persists despite discontinuation or reduction of other antihypertensive medications, a dose reduction or interruption of sparsentan should be considered. Transient hypotensive reactions are not a contraindication to further administration of sparsentan, which may be administered once blood pressure has stabilized.

5. Monitor kidney function regularly. If a patient develops a clinically significant decrease in renal function while receiving sparsentan, consideration should be given to withholding or discontinuing treatment.

6. Monitor serum potassium regularly and provide appropriate treatment. Patients with end-stage renal disease or who are concurrently taking potassium-raising medications (e.g., potassium supplements, potassium-sparing diuretics) or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia. A dose reduction or discontinuation of sparsentan may be required.

7. If clinically significant fluid retention occurs, the patient should be evaluated to determine the cause and whether it is necessary to initiate or adjust the dose of diuretic therapy and then consider adjusting sparsentan. For more information about sparsentan, please refer to the package insert.

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