Vadadustat (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- VAFSEO
Boxed Warning
VAFSEO increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE) [see Warnings and Precautions (5.1)]. 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 [see Warnings and Precautions (5.1)]. No trial has identified a hemoglobin target level, dose of VAFSEO, or dosing strategy that does not increase these risks [see Dosage and Administration (2.4)]. Use the lowest dose of VAFSEO sufficient to reduce the need for red blood cell transfusions [see Dosage and Administration (2.4)].
Indications and Usage
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 [see Warnings and Precautions (5.6)].
Contraindications
VAFSEO is contraindicated in patients: with a known hypersensitivity to VAFSEO or any of its components [see Description (11)]. with uncontrolled hypertension [see Warnings and Precautions (5.3)].
Adverse Reactions
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 [see Boxed Warning and Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Hypertension [see Warnings and Precautions (5.3)] Seizures [see Warnings and Precautions (5.4)] Gastrointestinal erosion [see Warnings and Precautions (5.5)] Serious adverse reactions in patients with anemia due to chronic kidney disease and not on dialysis [see Warnings and Precautions (5.6)]
Mechanism of Action
Vadadustat is a reversible inhibitor of HIF-prolyl-4-hydroxylases (PH)1, PH2, and PH3 (IC50 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).
Overdosage
VAFSEO overdose may result in exaggeration of the pharmacologic effects such as increased Hb. VAFSEO overdose should be managed as clinically appropriate (e.g., reduction of VAFSEO dose or discontinuation). Approximately 16% of the vadadustat dose is removed by dialysis. There is no specific antidote.