General MedicationsORALBlack Box

FILSPARI

SPARSENTAN

Standard Dose

2 DOSAGE AND ADMINISTRATION • Prior to initiating treatment with FILSPARI, discontinue use of renin- angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) ( 2.1 , 4 , 7.1 ). • Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to 400 mg once daily, as tolerated. When resuming FILSPARI after an interruption, consider re-titration ( 2.4 ). • Instruct patients to swallow tablets whole with water prior to the morning or evening meal ( 2.5 ). 2.1 General Considerations Prior to initiating treatment with FILSPARI, discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . 2.2 Monitoring Initiate treatment with FILSPARI only after measuring aminotransferase levels and total bilirubin. Avoid initiation in patients with elevated aminotransferases greater than 3 times ULN. Continue required monitoring every 3 months during treatment with FILSPARI [see Dosage and Administration ( 2.6 ), Warnings and Precautions ( 5.1 )]. 2.3 Pregnancy Testing Exclude pregnancy before initiating treatment with FILSPARI [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 , 8.3 )]. 2.4 Recommended Dosage Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to the recommended dose of 400 mg once daily, as tolerated. When resuming treatment with FILSPARI after an interruption, consider titration of FILSPARI, starting at 200 mg once daily. After 14 days, increase to the recommended dose of 400 mg once daily [see Drug Interactions ( 7.2 )] . 2.5 Administration • Instruct patient to swallow tablets whole with water prior to the morning or evening meal. • Maintain the same dosing pattern in relationship to meals. • If a dose is missed, take the next dose at the regularly scheduled time. Do not take double or extra doses. 2.6 Dosage Adjustment for Aminotransferase Elevations If aminotransferase levels increase, adjust monitoring and treatment plan according to Table 1 . Do not resume treatment in patients who have experienced clinical symptoms of hepatotoxicity or in patients whose hepatic enzyme levels and bilirubin have not returned to pretreatment levels. Table 1: Dosage Adjustment and Monitoring in Patients Developing Aminotransferase Elevations Greater Than 3 Times ULN ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = international normalized ratio; ULN = upper limit of normal. ALT/AST levels Treatment and monitoring recommendations Greater than 3 times and less than or equal to 8 times ULN Confirm elevation with a repeat measure. If confirmed, interrupt treatment, and monitor aminotransferase levels and bilirubin at least weekly, and INR as needed, until the levels return to pretreatment values and the patient is asymptomatic. Do not resume treatment if any of the following occurs without other cause found: • ALT or AST greater than 3 times ULN and total bilirubin greater than 2 times ULN or INR greater than 1.5 • ALT or AST greater than 3 times ULN, with symptoms of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (greater than 5% eosinophils) • ALT or AST greater than 5 times ULN for more than 2 weeks If treatment is resumed, initiate FILSPARI at 200 mg once daily, with reassessment of hepatic enzyme levels and bilirubin within 3 days. Close monitoring is required in these patients [see Dosage and Administration ( 2.2 , 2.4 )] . Greater than 8 times ULN Stop treatment permanently if no other cause found. 2.7 Dosage Modification for Concomitant Use with Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors with FILSPARI. If a strong CYP3A inhibitor cannot be avoided, interrupt treatment with FILSPARI [see Drug Interactions ( 7.2 )] .

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE FILSPARI is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

Summary

Indications and usage 1 INDICATIONS AND USAGE FILSPARI is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

FILSPARI is an endothelin and angiotensin II receptor antagonist indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression ( 1 , 12.1 ).

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE FILSPARI is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. FILSPARI is an endothelin and angiotensin II receptor antagonist indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression ( 1 , 12.1 ). Dosage and administration 2 DOSAGE AND ADMINISTRATION • Prior to initiating treatment with FILSPARI, discontinue use of renin- angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) ( 2.1 , 4 , 7.1 ). • Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to 400 mg once daily, as tolerated. When resuming FILSPARI after an interruption, consider re-titration ( 2.4 ). • Instruct patients to swallow tablets whole with water prior to the morning or evening meal ( 2.5 ). 2.1 General Considerations Prior to initiating treatment with FILSPARI, discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . 2.2 Monitoring Initiate treatment with FILSPARI only after measuring aminotransferase levels and total bilirubin. Avoid initiation in patients with elevated aminotransferases greater than 3 times ULN. Continue required monitoring every 3 months during treatment with FILSPARI [see Dosage and Administration ( 2.6 ), Warnings and Precautions ( 5.1 )]. 2.3 Pregnancy Testing Exclude pregnancy before initiating treatment with FILSPARI [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 , 8.3 )]. 2.4 Recommended Dosage Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to the recommended dose of 400 mg once daily, as tolerated. When resuming treatment with FILSPARI after an interruption, consider titration of FILSPARI, starting at 200 mg once daily. After 14 days, increase to the recommended dose of 400 mg once daily [see Drug Interactions ( 7.2 )] . 2.5 Administration • Instruct patient to swallow tablets whole with water prior to the morning or evening meal. • Maintain the same dosing pattern in relationship to meals. • If a dose is missed, take the next dose at the regularly scheduled time. Do not take double or extra doses. 2.6 Dosage Adjustment for Aminotransferase Elevations If aminotransferase levels increase, adjust monitoring and treatment plan according to Table 1 . Do not resume treatment in patients who have experienced clinical symptoms of hepatotoxicity or in patients whose hepatic enzyme levels and bilirubin have not returned to pretreatment levels. Table 1: Dosage Adjustment and Monitoring in Patients Developing Aminotransferase Elevations Greater Than 3 Times ULN ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = international normalized ratio; ULN = upper limit of normal. ALT/AST levels Treatment and monitoring recommendations Greater than 3 times and less than or equal to 8 times ULN Confirm elevation with a repeat measure. If confirmed, interrupt treatment, and monitor aminotransferase levels and bilirubin at least weekly, and INR as needed, until the levels return to pretreatment values and the patient is asymptomatic. Do not resume treatment if any of the following occurs without other cause found: • ALT or AST greater than 3 times ULN and total bilirubin greater than 2 times ULN or INR greater than 1.5 • ALT or AST greater than 3 times ULN, with symptoms of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (greater than 5% eosinophils) • ALT or AST greater than 5 times ULN for more than 2 weeks If treatment is resumed, initiate FILSPARI at 200 mg once daily, with reassessment of hepatic enzyme levels and bilirubin within 3 days. Close monitoring is required in these patients [see Dosage and Administration ( 2.2 , 2.4 )] . Greater than 8 times ULN Stop treatment permanently if no other cause found. 2.7 Dosage Modification for Concomitant Use with Strong CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors with FILSPARI. If a strong CYP3A inhibitor cannot be avoided, interrupt treatment with FILSPARI [see Drug Interactions ( 7.2 )] . Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Hypotension ( 5.4 ) • Acute Kidney Injury ( 5.5 ) • Hyperkalemia ( 5.6 ) • Fluid Retention ( 5.7 ) 5.1 Hepatotoxicity Elevations in ALT or AST of at least 3-fold ULN have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge [see Adverse Reactions ( 6.1 )] . While no concurrent elevations in bilirubin greater than 2-times ULN or cases of liver failure were observed in FILSPARI-treated patients in clinical trials, some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure. To reduce the

Boxed Warning

WARNING: HEPATOTOXICITY and EMBRYO-FETAL TOXICITY Because of the risk of hepatotoxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions ( 5.1 , 5.2 )] . Hepatotoxicity Some Endothelin Receptor Antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. In clinical studies, elevations in aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal (ULN) have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. Measure transaminases and bilirubin before initiating treatment and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3-times ULN [see Dosage and Administration ( 2.2 , 2.6 ), Warnings and Precautions ( 5.1 )] . FILSPARI should generally be avoided in patients with elevated aminotransferases (>3-times ULN) at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity [see Dosage and Administration ( 2.2 , 2.6 ), Warnings and Precautions ( 5.1 )] . Embryo-Fetal Toxicity FILSPARI is contraindicated for use during pregnancy because it may cause fetal harm if used by pregnant patients. Therefore, in patients who can become pregnant, exclude pregnancy prior to initiation of FILSPARI. Advise use of effective contraception before the initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with FILSPARI. When pregnancy is detected, discontinue FILSPARI as soon as possible [see Dosage and Administration ( 2.3 ), Contraindications ( 4 ), Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 , 8.3 )]. WARNING: HEPATOTOXICITY and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. • FILSPARI is only available through a restricted distribution program called the FILSPARI Risk Evaluation and Mitigation Strategies (REMS) because of the risk of hepatotoxicity ( 5.2 ): • Some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure ( 5.1 ). • Measure liver aminotransferases and total bilirubin prior to initiation of treatment and ALT and AST every 3 months during treatment ( 2.2 , 2.6 , 5.1 ). • Interrupt treatment and closely monitor patients developing aminotransferase elevations more than 3-times Upper Limit of Normal (ULN) ( 2.2 , 2.6 ). • Based on animal data, FILSPARI may cause fetal harm if used during pregnancy and is contraindicated in pregnancy ( 4 , 5.3 , 8.1 ). • For patients who can become pregnant, exclude pregnancy prior to the initiation of treatment with FILSPARI ( 2.3 , 5.3 , 8.3 ) • Use effective contraception prior to initiation of treatment, during treatment, and for two weeks after stopping FILSPARI ( 4 , 5.3 , 8.1 , 8.3 ). • When pregnancy is detected, discontinue FILSPARI as soon as possible ( 5.3 ).

Monitoring

• 5 WARNINGS AND PRECAUTIONS • Hypotension ( 5.4 ) • Acute Kidney Injury ( 5.5 ) • Hyperkalemia ( 5.6 ) • Fluid Retention ( 5.7 ) 5.1 Hepatotoxicity Elevations in ALT or AST of at least 3-fold ULN have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge [see Adverse Reactions ( 6.1 )] .
• While no concurrent elevations in bilirubin greater than 2-times ULN or cases of liver failure were observed in FILSPARI-treated patients in clinical trials, some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure.
• To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and then every 3 months during treatment [See Dosage and Administration ( 2.2 )] .
• 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 FILSPARI and seek medical attention.