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General Information
Vafseo (vadadustat) is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor.
Vafseo is specifically indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months.
Dosage/Administration
- Vafseo is supplied as tablets for oral administration.
- The recommended starting dose is 300 mg orally once daily, with or without food.
- Monitor hemoglobin levels when initiating or adjusting dose and then monthly.
- 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.
- Individualize dosing and use the lowest dose of Vafseo sufficient to reduce the need for red blood cell transfusions. Do not target a hemoglobin level higher than 11 g/dL.
- Vafseo can be taken with or without food.
- Vafseo should be swallowed whole. Tablets should not be cut, crushed, or chewed.
- Vafseo can be administered without regard to the timing or type of dialysis.
- If a dose of Vafseo is missed, it should be taken as soon as possible, unless it is the same day as the next dose. In this case, the missed dose should be skipped, and the next dose taken at the usual time. Double doses should not be taken to make-up for a missed dose.
Mechanism of Action
Vafseo (vadadustat) is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor. This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, and increased production of erythropoietin (EPO).
Side Effects
Side effects associated with the use of Vafseo may include, but are not limited to, the following:
- hypertension
- diarrhea
The Vafseo drug label comes with the following Black Box Warning: Vafseo 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. No trial has identified a hemoglobin target level, dose of Vafseo, or dosing strategy that does not increase these risks. Use the lowest dose of Vafseo sufficient to reduce the need for red blood cell transfusion.
Clinical Trial Results
The FDA approval of Vafseo was based on data from the INNO2VATE program and an assessment of post marketing safety data from Japan where Vafseo was launched in August 2020.
Two randomized, open-label, noninferiority phase 3 trials evaluated the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial.
The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event.
In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group. The mean differences between the groups in the change in hemoglobin concentration were −0.31 g per deciliter at weeks 24 to 36 and −0.07 g per deciliter at weeks 40 to 52 in the incident DD-CKD trial and −0.17 g per deciliter and −0.18 g per deciliter, respectively, in the prevalent DD-CKD trial.
The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively.