司帕生坦的副作用如何缓解

Sparsentan is a new drug used to treat primary immunoglobulin A nephropathy and focal segmental glomerulosclerosis. It has dual endothelin and angiotensin II receptor antagonistic effects. Although it is effective in reducing proteinuria and delaying the deterioration of renal function, it also brings a series of side effects, such as liver toxicity, hypotension, hyperkalemia, etc.

Side effects of sparsentan

It may cause a variety of adverse reactions in clinical use, mainly related to its dual receptor antagonistic mechanism. Understanding these side effects can help patients and doctors identify and intervene promptly.

Hepatotoxicity

Sparsentan may cause an increase in aminotransferases and even cause liver damage in severe cases. Symptoms include nausea, vomiting, right upper quadrant pain, jaundice, etc. In clinical trials, some patients experienced ALT or AST elevations exceeding three times the upper limit of normal values.

Hypotension

Because sparsentan inhibits angiotensin II receptors, some patients may experience hypotension, manifesting as dizziness, fatigue, and even orthostatic hypotension.

Hyperkalemia and acute kidney injury

Sparsentan may interfere with potassium metabolism, leading to an increase in blood potassium and, in severe cases, arrhythmia. At the same time, it may reduce the glomerular filtration rate and cause acute kidney injury, especially in patients whose renal function depends on the RAAS system.

In addition to the above-mentioned major side effects, sparsentan may also cause peripheral edema, anemia and drug interactions. Patients need to closely monitor relevant indicators under the guidance of a doctor.

How to alleviate the side effects of sparsentan

Individualized mitigation strategies should be adopted for the different side effects of sparsentan to reduce the risk of adverse reactions and maintain the therapeutic effect.

Management of hepatotoxicity

Baseline liver function needs to be tested before treatment, and transaminase and bilirubin levels should be monitored monthly for 12 months before treatment. If ALT or AST exceeds 3 times the upper limit of normal, medication should be suspended and liver function should be reviewed weekly. If symptoms of hepatotoxicity (such as jaundice, right upper quadrant pain) occur, the drug must be permanently discontinued.

Response to hypotension

Initial treatment should start with 200 mg/d and adjust to 400 mg/d after 14 days based on tolerance. If hypotension occurs, other antihypertensive drugs can be reduced or discontinued and appropriate blood volume maintained. Patients with severe hypotension need to temporarily stop taking the drug and re-titrate the dose after blood pressure stabilizes.

Hyperkalemia and renal function monitoring

Regularly monitor serum potassium and renal function, and avoid combined use with potassium-sparing diuretics or potassium supplements. Mild hyperkalemia can be controlled with a low-potassium diet and diuretics, while severe cases require emergency potassium-lowering treatment. If renal function declines significantly, suspension or discontinuation of sparsentan therapy should be considered.

For peripheral edema, sodium intake can be restricted and diuretics can be used; patients with anemia can supplement iron, and all adjustments should be made under the guidance of a doctor.

Contraindications of Sparsentan

In some specific groups or situations, the use of Sparsentan may bring serious risks and must be strictly avoided.

Contraindicated in pregnant women

Sparsentan is embryo-fetal toxic and may cause birth defects or fetal death. Women of childbearing age need to confirm a negative pregnancy test before taking the drug, and take effective contraceptive measures during treatment and 1 month after stopping the drug.

Drug interaction contraindications

It is prohibited to combine with ARB drugs, endothelin receptor antagonists (ERA) or aliskiren, otherwise the risk of adverse reactions may increase. Strong CYP3A inhibitors will increase the plasma concentration of spaxentan and should be avoided together.

Use with caution in patients with hepatic insufficiency

Disabled in patients with transaminase >3 times the upper limit of normal. Patients with hepatic insufficiency should use it with caution and strengthen monitoring. If symptoms of hepatotoxicity occur or liver enzymes continue to rise, the drug should be permanently discontinued.

Sparsentan needs to be obtained through REMS restricted projects, and both prescribers and pharmacies require special certification. Patients should fully understand the risks of the drug and use it under professional medical supervision.