Recommended Dosage, Dose Adjustments, Renal Dose Adjustments

Sparsentan is the first dual pathway blocker. Its usage and dosage should be determined based on each patient's specific condition. The recommended starting dose is 200 mg daily, which can then be gradually adjusted based on the patient's tolerance to the medication and therapeutic effect.

Sparsentan Dosage and Administration

1. Recommended Dosage

(1) Initial Dose: Take 200 mg of sparsentan orally, once daily, for 14 consecutive days.

(2) Maintenance Dose: After completing the initial course, if the patient does not experience intolerance, increase the dose to 400 mg of sparsentan orally, once daily.

(3) Important Considerations: If treatment with sparsentan is interrupted and then restarted, consider gradual dose escalation: restart with the initial dose of 200 mg daily for 14 days, then increase to the recommended maintenance dose of 400 mg daily.

2. Method of Administration

Instruct patients to swallow the tablet whole with water, either in the morning or evening before a meal. The timing of medication intake relative to meals should be kept consistent, for example, always taken before a meal.

3. Missed Dose

If a dose is missed accidentally, take the next dose at the regularly scheduled time. Do not take a double dose or an extra dose to make up for a missed one.

Sparsentan Dose Adjustments

1. Renal Function Adjustment

For patients whose renal function may be partially dependent on the activity of the renin-angiotensin-aldosterone system, such as those with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion, sparsentan should be used with caution. No specific dose adjustment method is currently recommended. If a clinically significant decline in renal function occurs during treatment, consider pausing or discontinuing treatment.

2. Hepatic Function Adjustment and Dose Adjustment

Sparsentan should preferably not be used as initial treatment in patients with baseline transaminase levels exceeding 3 times the upper limit of normal, or in patients with any degree of hepatic impairment (Child-Pugh Class A, B, or C), as the risk of hepatotoxicity is significantly increased and monitoring becomes more difficult in these populations.

3. Transaminase Elevation During Treatment

If ALT/AST is between >3x and ≤8x the upper limit of normal (ULN):

(1) Confirm the elevation with a repeat transaminase test; if confirmed, suspend sparsentan treatment.

(2) Monitor transaminase and bilirubin levels at least weekly, and INR if necessary, until the patient is asymptomatic and levels return to pre-treatment baseline.

(3) If transaminase levels return to pre-treatment levels, consider reinitiating sparsentan at a starting dose of 200 mg daily.

(4) Recheck transaminase and bilirubin levels within 3 days after reinitiating sparsentan, and monitor closely thereafter.

If ALT/AST exceeds 8x ULN: If no other cause is found, sparsentan treatment should be permanently discontinued.

4. Conditions Where Reinitiating Sparsentan is Not Recommended

(1) ALT or AST elevation >3x ULN accompanied by total bilirubin >2x ULN, or INR >1.5.

(2) ALT or AST elevation >3x ULN accompanied by symptoms of hepatotoxicity (e.g., nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or pruritus) and/or eosinophilia.

(3) ALT or AST >5x ULN that persists for more than two weeks.

(4) Patients who have previously experienced clinical symptoms of hepatotoxicity.

(5) Patients whose liver enzymes and bilirubin have not returned to pre-treatment levels.