VANRAFIA (atrasentan hydrochloride)

Atrasentan area under the time concentration curve (AUC) is dose proportional across the 0.35 mg to 30 mg (0.47 to 40 times the approved recommended dosage) dose range. Atrasentan steady state plasma concentrations are reached within 7 days with 2- to 3-fold accumulation.

AbsorptionAtrasentan time to peak plasma concentration (T max ) is approximately 0.5 hour. Effect of Food No clinically significant differences in atrasentan pharmacokinetics were observed following administration with a high-...

14.1 IgA Nephropathy The effect of VANRAFIA on proteinuria was assessed in a randomized, double-blind, placebo-controlled, multicenter, global study (ALIGN, NCT04573478) in adults with biopsy-proven primary IgAN, an eGFR ≥ 30 mL/min/1.73 m 2 , and urine protein ≥ 1 g/day on a stable dose of maximally tolerated renin angiotensin system inhibitor. The study included two cohorts: a main cohort of 340 patients and an exploratory cohort of 64 patients who were also on a stable dose of sodium glucose co-transporter 2 inhibitor (SGLT2i) at baseline. Patients with chronic kidney disease due to another...

The following clinically significant adverse reactions are described elsewhere in the labeling: Embryo-fetal Toxicity [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Fluid Retention [see Warnings and Precautions (5.3)] Decreased Sperm Counts [see Warnings and Precautions (5.4)] Most common adverse reactions (incidence ≥ 5%) were peripheral edema and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-88...

Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy Use of VANRAFIA is contraindicated in patients who are pregnant [see Dosage and Administration (2.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)] . 4.2 Hypersensitivity VANRAFIA is contraindicated in patients with a history of a hypersensitivity reaction to atrasentan or any component of the product.

Hepatotoxicity ( 5.2 ) Fluid Retention ( 5.3 ) Decreased Sperm Counts ( 5.4 , 8.3 ) 5.1 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. Counsel patients who can become pregnant of the potential risk to a fetus....

7 DRUG INTERACTIONS Strong or moderate CYP3A inducers: Avoid concomitant use. ( 7.1 ) OATP1B1/1B3 inhibitors: Avoid concomitant use. ( 7.1 ) 7.1 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 [see Clinical Pharmacology (12.3)] . Concomitant use with a strong and moderate CYP3A induce...