司帕生坦出现肝脏毒性怎么处理?

Sparsentan is a drug that treats primary immunoglobulin A nephropathy (IgAN). If hepatotoxicity occurs, management is as follows:

Patients should be monitored for transaminases and total bilirubin levels before starting treatment and monthly for the first 12 months of treatment. During subsequent treatment with sparsentan, monitoring is also required every 3 months. This reduces the patient's potential risk of severe hepatotoxicity.

It is recommended that patients who develop symptoms suggestive of hepatotoxicity (nausea, fatigue, anorexia, jaundice, vomiting, right upper quadrant pain, dark urine, fever, or itching) should immediately stop treatment with sparsentan and seek medical attention. If transaminase levels are abnormal at any time during treatment, spaxentan therapy should be interrupted and monitored as recommended.

If the patient's transaminase levels change during treatment, dosing should also be suspended and the patient should be monitored. Resumption of medication should be considered only when transaminases and bilirubin levels return to pretreatment levels without any symptoms.

Prior to initiating dosing, patients with elevated transaminases (>3x ULN) should avoid initiating spaxentan therapy as the risk of severe hepatotoxicity may be increased in these patients.

For liver toxicity caused by sparsentan, it is important to detect and stop the drug in time, then seek medical treatment as soon as possible and handle it according to the doctor's recommendations. At the same time, regular monitoring of transaminase and bilirubin levels is also an important means to prevent hepatotoxicity.

For more information on the precautions of Sparsentan, please click: This article details the precautions of this drug.

Efficacy of spasentan

PROTECT was an international, randomized, double-blind, active-controlled study comparing spasentan with irbesartan in adults (age ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1-0 g/day or more after at least 12 weeks of maximal therapy with a renin-angiotensin system inhibitor. Participants were randomly assigned in a 1:1 ratio to receive either sparsentan 400 mg once daily or irbesartan 300 mg once daily.

Results

404 participants were randomly assigned and treated with spaxentan or irbesartan. At week 36, the geometric least squares mean percentage change in urine protein-to-creatinine ratio from baseline was significantly higher in the irbesartan group than in the irbesartan group, with a relative reduction of 41% between groups.

Trial Conclusions

In adults with IgA nephropathy, once-daily treatment with sparsentan significantly reduced proteinuria compared with irbesartan. The safety profile of spasentan is similar to that of irbesartan. After the two-year double-blind period, future analyzes will show whether these beneficial effects translate into sparsentan's potential for long-term kidney protection.

Sparsentan medication for special groups

1. The use of Sparsentan in pregnant patients may cause harm to the fetus, and Sparsentan is contraindicated during pregnancy.

2. Patients are advised not to breastfeed during treatment with sparsentan.

3. The safety and efficacy of sparsentan in pediatric patients have not yet been determined.

4. Due to the potential risk of severe liver damage, any patient with liver damage should avoid using sparsentan.

5. Overdosage of sparsentan may lead to lowering of blood pressure. If overdose occurs, you should contact your doctor promptly for symptomatic treatment.

6. Sparsentan must not be used in combination with angiotensin receptor blockers (ARB), ERA or aliskiren.

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References

Heerspink HJL, Radhakrishnan J, Alpers CE, Barratt J, Bieler S, Diva U, Inrig J, Komers R, Mercer A, Noronha IL, Rheault MN, Rote W, Rovin B, Trachtman H, Trimarchi H, Wong MG, Perkovic V; PROTECT Investigators. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomized, double-blind, active-controlled clinical trial. Lancet. 2023 May 13;401(10388):1584-1594. doi: 10.1016/S0140-6736(23)00569-X. Epub 2023 Apr 1. PMID: 37015244.