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Precautions of Sparsentan

1. Hepatotoxicity

Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with sparsentan and seek medical attention. If aminotransferase levelsare abnormal at any time during treatment, interrupt sparsentan and monitor as recommended.

Consider re-initiation of sparsentan only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity.

Avoid initiation of sparsentan in patients with elevated aminotransferases (>3x ULN) prior to drug initiation because monitoring hepatotoxicity in these patients may be more difficult and these patients may be at increased risk for serious hepatotoxicity.

2. Embryo-Fetal Toxicity

Based on data from animal reproduction studies, sparsentan can cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancytest prior to initiation of treatment with sparsentan, monthly during treatment, and one month after discontinuation of treatment. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with sparsentan.

3.sparsentan REMS

For all patients, sparsentan is available only through a restricted program under a REMS called the sparsentan REMS because of the risk of hepatotoxicity and embryo-fetal toxicity.

4. Hypotension

Hypotension has been observed in patients treated with ARBs and endothelin receptor antagonists (ERAs) and was observed in clinical studies with sparsentan. In the PROTECT trial, there was a greater incidence of hypotension-associated adverse events, some serious, including dizziness, in patients treated with sparsentan compared to irbesartan.

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 a dose reduction or dose interruption of sparsentan. A transient hypotensive response is not a contraindication to further dosing of sparsentan, which can be given once blood pressure has stabilized.

5. Acute Kidney Injury

Monitor kidney function periodically. Drugs that inhibit the renin-angiotensin system can cause acute kidney injury. Patients whose kidney function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute kidney injury on sparsentan. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function while on sparsentan.

from FDA，2023.02