Atrasentan

VANRAFIA is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g. This indication is approved under accelerated approval based on a reduction of proteinuria. It has not been established whether VANRAFIA slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. VANRAFIA is an endothelin receptor antagonist indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g.

Atrasentan is an ET A receptor antagonist (Ki = 0.034 nM) with >1800-fold selectivity for the ET A receptor compared to the endothelin type B receptor (Ki = 63.3 nM). Endothelin (ET)-1 is thought to contribute to the pathogenesis of IgAN via the ET A R.

0.75 mg orally once daily with or without food Pregnancy Testing Exclude pregnancy before initiating VANRAFIA.

Pregnancy. Hypersensitivity Pregnancy Use of VANRAFIA is contraindicated in patients who are pregnant.

Boxed warning (embryo-fetal toxicity vanrafia): is contraindicated for use in pregnant patients, it may cause major birth defects based on animal data. Exclude pregnancy prior to initiation of treatment with VANRAFIA. Advise use of effective contraception before the initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with VANRAFIA. Stop VANRAFIA as soon as possible if the patient becomes pregnant. Hepatotoxicity. Fluid Retention. Decreased Sperm Counts Embryo-Fetal Toxicity Based on data from animal reproduction studies, VANRAFIA may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for endothelin receptor antagonists do not establish the presence or absence of major birth defects related to the use of VANRAFIA.

The following clinically significant adverse reactions are described elsewhere in the labeling: Embryo-fetal Toxicity Hepatotoxicity Fluid Retention Decreased Sperm Counts Most common adverse reactions (incidence ≥ 5%) were peripheral edema and anemia.

Strong or moderate CYP3A inducers: Avoid concomitant use. OATP1B1/1B3 inhibitors: Avoid concomitant use. Effect of Other Drugs on VANRAFIA Strong or Moderate CYP3A Inducers Avoid concomitant use with a strong or moderate CYP3A inducer. Atrasentan is a CYP3A substrate. Concomitant use with a strong and moderate CYP3A inducer is expected to decrease atrasentan exposure, which may reduce VANRAFIA efficacy. OATP1B1/1B3 Inhibitors Avoid concomitant use with organic anion transporting polypeptides 1B1/1B3 (OATP1B1/1B3) inhibitors. Atrasentan is a OATP1B1/1B3 substrate. Concomitant use with a OATP1B1/1B3 inhibitor increases atrasentan exposure, which may increase the risk of VANRAFIA adverse reactions.

Storage Store at 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F). Store and dispense VANRAFIA in its original container.