Can spaxentan cause liver toxicity?

Can cause liver poisoning.

Elevations in ALT or AST of at least 3 times the ULN have been observed in up to 2.5% of patients treated with sparsentane, including cases confirmed by rechallenge.

Although concurrent bilirubin elevations >2 times the ULN or hepatic failure have not been observed in patients treated with sparsentane in clinical trials, some endothelin receptor antagonists can cause elevated transaminases, hepatotoxicity, and hepatic failure.

How to prevent or treat liver poisoning

1. In order to reduce the risk of potential severe hepatotoxicity, serum aminotransferase levels and total bilirubin levels should be measured before starting treatment with sparsentane, and measured once a month for the first 12 months, and then measured every 3 months during treatment. Treatment with sparsentan can only be started after testing the transaminase levels and total transaminase levels.

2. It is recommended that patients who develop symptoms of hepatotoxicity during medication treatment, such as nausea, vomiting, right upper quadrant pain, fatigue, anorexia, xanthelasma, dark urine, fever or itching, should stop treatment immediately and seek medical attention in time.

3. If abnormal transaminase levels occur during treatment, interrupt sparsentane treatment and monitor as recommended.

4. Restart treatment with sparsentan should be considered when liver enzyme levels and bilirubin return to pre-treatment levels, and only in patients who do not develop clinical symptoms of hepatotoxicity.

5. Avoid using sparsentane in patients with elevated transaminases (3 times ULN). Monitoring for hepatotoxicity in these patients may be more difficult, and these patients may be at increased risk for severe hepatotoxicity.

6. Sparsentane treatment cannot be resumed in patients who develop clinical symptoms of hepatotoxicity or whose liver enzyme levels and bilirubin have not returned to pre-treatment levels.

sparsetan

The starting dose of treatment is 200 mg once daily. After 14 days, increase to 400 mg once daily. When resuming treatment with sparsentane after an interruption, consider titration starting with 200 mg once daily and increasing to the recommended dose of 400 mg once daily after 14 days.

Sparsentin needs to be swallowed whole tablet with water before breakfast or dinner, maintaining the same dosing pattern as with meals.

drug interactions

1. Renin-angiotensin system (RAs) preparations and RAS: Sparsentan cannot be taken simultaneously with ARBs, ERAs or aliskiren. Combined use will increase the risk of hypotension, syncope, hyperkalemia and changes in renal function.

2. CYP3A inhibitors: Avoid co-administration of sparsentan with CYP3A inhibitors. If strong CYP3A inhibitors cannot be avoided, interrupt sparsentan treatment. Consider dose titration when resuming treatment with sparsentane.

3. Strong CYP3A inducer: Sparsentan is a CYP3A substrate, and simultaneous use with strong CYP3A inducers can reduce the Cmax and AUC of sparsentan and reduce the efficacy of sparsentan.

4. Antacids and acid reducers: They need to be taken at intervals with sparsentane. They can be taken 2 hours before or after taking antacids to avoid taking them at the same time to reduce the exposure of sparsentane and thus reduce the efficacy.

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