Sparsentan (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- FILSPARI
Boxed Warning
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)].
Contraindications
Use of FILSPARI is contraindicated in patients who are pregnant [see Dosage and Administration (2.3), Warnings and Precautions (5.3), Use in Specific Populations (8.1)]. Do not co-administer FILSPARI with ARBs, ERAs, or aliskiren [see Dosage and Administration (2.1), Drug Interactions (7.1)].
Adverse Reactions
Clinically significant adverse reactions that appear in other sections of the label include: •Hepatotoxicity [see Warnings and Precautions (5.1)] •Embryo-Fetal Toxicity [see Warnings and Precautions (5.3)] •Hypotension [see Warnings and Precautions (5.4)] •Acute Kidney Injury [see Warnings and Precautions (5.5)] •Hyperkalemia [see Warnings and Precautions (5.6)] •Fluid Retention [see Warnings and Precautions (5.7)]
Mechanism of Action
Sparsentan is a single molecule with antagonism of the endothelin type A receptor (ETAR) and the angiotensin II type 1 receptor (AT1R). Sparsentan has high affinity for both the ETAR (Ki= 12.8 nM) and the AT1R (Ki=0.36 nM), and greater than 500-fold selectivity for these receptors over the endothelin type B and angiotensin II subtype 2 receptors. Endothelin 1 and angiotensin II are thought to be involved in the pathogenesis of IgAN and FSGS via the ETAR and AT1R, respectively.
Overdosage
There is no experience with overdose with FILSPARI. Sparsentan has been given in doses up to 1600 mg/day in healthy volunteers, or up to 800 mg/day in patients. Overdose of FILSPARI may result in decreased blood pressure. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because sparsentan is highly protein-bound.