Vadadustat

VAFSEO is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months. Limitations of Use VAFSEO has not been shown to improve quality of life, fatigue, or patient well-being. VAFSEO is not indicated for use: As a substitute for red blood cell transfusions in patients who require immediate correction of anemia In patients with anemia due to CKD not on dialysis. VAFSEO is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months. Limitations of Use Not been shown to improve quality of life, fatigue, or patient well-being. Not indicated for use: As a substitute for transfusion in patients requiring immediate correction of anemia.

Vadadustat is a reversible inhibitor of HIF-prolyl-4-hydroxylases (PH)1, PH2, and PH3 (IC 50 in the nM range). This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, and increased production of erythropoietin (EPO).

Recommended starting dose is 300 mg orally once daily, with or without food. Monitor hemoglobin levels when initiating or adjusting dose and then monthly. ( 2.1 and 2.4 ) Increase the dose no more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Adjust dose in increments of 150 mg to achieve or maintain hemoglobin levels of 10 g/dL to 11 g/dL. Doses may range from 150 mg to a maximum of 600 mg.

VAFSEO is contraindicated in patients: with a known hypersensitivity to VAFSEO or any of its components. with uncontrolled hypertension. Known hypersensitivity to VAFSEO or any of its components. Uncontrolled hypertension

Boxed warning: increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels. Hepatotoxicity: Has been reported in patients taking VAFSEO. Measure ALT, AST and bilirubin prior to the initiation of VAFSEO, monthly after initiation for the first 6 months, then as clinically indicated. Discontinue VAFSEO if ALT or AST is persistently elevated or accompanied by elevated bilirubin. Hypertension: Worsening hypertension, including hypertensive crisis may occur. Monitor blood pressure. Adjust anti-hypertensive therapy as needed. Seizures: Seizures have occurred in patients with CKD taking VAFSEO.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access Hepatotoxicity Hypertension Seizures Gastrointestinal erosion Serious adverse reactions in patients with anemia due to chronic kidney disease and not on dialysis The most common adverse reactions (occurring at ≥ 10%) were hypertension and diarrhea.

Iron supplements and iron-containing phosphate binders: Administer VAFSEO at least 1 hour before products containing iron. Non-iron-containing phosphate binders: Administer VAFSEO at least 1 hour before or 2 hours after non-iron-containing phosphate binders. BCRP substrates: Monitor for signs of substrate adverse reactions and consider substrate dose reduction. Statins: Monitor for statin-related adverse reactions.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).