Vadadustat

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).

• 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.ICD-10: D64.9, N18.9

• 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 )] .contraindicated

Recommended starting dose is 300 mg orally once daily, with or without food. ( 2.3 ) 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. ( 2.4 ) 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. ( 2.4 ) 2.1 Pre-Treatment and On-Treatment Evaluations of Anemia, Iron Stores, and Liver Tests Evaluation of Anemia and Iron Stores Correct and exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding) before initiation of VAFSEO. Evaluate iron status in all patients before and during treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of therapy. Measure hemoglobin (Hb) at baseline and as recommended in section 2.4 . Liver Testing Measure serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin prior to the initiation of VAFSEO and monthly after initiation for the first 6 months and then monitor as clinically indicated [see Warnings and Precautions ( 5.2 )] .

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. ( 5.2 ) Hypertension: Worsening hypertension, including hypertensive crisis may occur. Monitor blood pressure. Adjust anti-hypertensive therapy as needed. ( 5.3 ) Seizures: Seizures have occurred in patients with CKD taking VAFSEO. Monitor for new-onset seizures, premonitory symptoms, or change in seizure frequency. ( 5.4 ) Gastrointestinal Erosion: Gastric or esophageal erosions and gastrointestinal bleeding have been reported. ( 5.5 ) Malignancy: May have unfavorable effects on cancer growth. Not recommended if active malignancy. ( 5.7 ) 5.1 Increased Risk of Death, Myocardial Infarction (MI), Stroke, Venous Thromboembolism, and Thrombosis of Vascular Access VAFSEO increases the risk of arterial and venous thrombotic events, that may be fatal, including myocardial infarction, stroke, venous thromboembolism and vascular access thrombosis [see Boxed Warning , Adverse Reactions ( 6.1 )] . Patients with cardiovascular or cerebrovascular disease are at increased risk of these events. Avoid use in patients with a history of myocardial infarction, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting VAFSEO. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.

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 )] The most common adverse reactions (occurring at ≥ 10%) were hypertension and diarrhea. ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Akebia Therapeutics, Inc. at 1-844-445-3799 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of VAFSEO was evaluated in adults with dialysis-dependent chronic kidney disease (DD-CKD) with anemia in the INNO 2 VATE-1 and INNO 2 VATE-2 trials [see Clinical Studies ( 14.1 )] . Both trials randomized patients to VAFSEO or darbepoetin alfa. Results in this section are based on the pooled VAFSEO treatment arms and pooled darbepoetin alfa arms from these trials.

Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended until two days after the final dose. ( 8.2 ) Hepatic Impairment: Not recommended for use in patients with cirrhosis or active, acute liver disease. ( 8.6 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VAFSEO during pregnancy. Health care providers and patients are encouraged to report pregnancies by calling 1-844-445-3799. Risk Summary Available data with VAFSEO use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with CKD (see Clinical Considerations) . Vadadustat administration orally to pregnant rats and rabbits during the period of organogenesis was associated with reduced fetal weight at doses that caused maternal toxicity. In rat and rabbit studies, vadadustat was not teratogenic (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Metabolism

Vadadustat AUC and observed peak concentration (C max ) increased proportionally after single doses from 80 mg to 1200 mg (0.27 to 4 times the approved recommended starting dosage). Vadadustat is expected to reach steady state by day 3 following once daily dosing, with no significant accumulation.

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.

• Mar 27, 2024NDANDA215192Akebia

1. 1Haemoglobin Decreased166.5%
2. 2Death156.1%
3. 3Marasmus145.7%
4. 4Off Label Use145.7%
5. 5Cardiac Failure135.3%
6. 6Diarrhoea124.9%
7. 7Drug Interaction124.9%
8. 8Pneumonia114.5%
9. 9Nausea104.0%
10. 10Cardiac Failure Congestive93.6%
11. 11Rhabdomyolysis93.6%
12. 12Haemoglobin Increased83.2%
13. 13Pneumonia Aspiration83.2%
14. 14Product Use Issue83.2%
15. 15Cardiac Failure Chronic72.8%

The 10 most recently updated of 42 ClinicalTrials.gov registrations naming Vadadustat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Safety and Efficacy of a Phased Transition From Epogen to Three Times Weekly Oral Vadadustat for the Treatment of Anemia in Subjects Receiving In-Center Hemodialysis
  Not yet recruiting · Phase 3 · Interventional · 100 enrolled · Geoff Block
  NCT07565701updated 2026-05-04
• Effects of Vadadustat on Anemia, Quality of Life, and Inflammation in Dialysis Patients
  Not yet recruiting · Phase 4 · Interventional · 40 enrolled · Mackay Memorial Hospital
  NCT07537816updated 2026-04-23
• Efficacy and Safety Study to Evaluate MT-6548 in Peritoneal Dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
  Completed · Phase 3 · Interventional · 42 enrolled · Tanabe Pharma Corporation
  NCT03402386updated 2026-04-06
• Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Currently Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan
  Completed · Phase 3 · Interventional · 323 enrolled · Tanabe Pharma Corporation
  NCT03439137updated 2026-04-06
• Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Not Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan
  Completed · Phase 3 · Interventional · 24 enrolled · Tanabe Pharma Corporation
  NCT03461146updated 2026-04-06
• Effects of Iron Supplements on the Pharmacokinetics of MT-6548
  Completed · Phase 3 · Interventional · 61 enrolled · Tanabe Pharma Corporation
  NCT03645863updated 2026-04-06
• Efficacy and Safety Study to Evaluate MT-6548 in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
  Completed · Phase 3 · Interventional · 304 enrolled · Tanabe Pharma Corporation
  NCT03329196updated 2026-04-06
• Vafseo Outcomes In-Center Experience
  Active not recruiting · Phase 3 · Interventional · 2,200 enrolled · USRC Kidney Research
  NCT06520826updated 2026-03-10
• To Evaluate the Efficacy of Three Times Weekly (TIW) Vadadustat Compared to Standard of Care ESA in Patients With Anemia of CKD Receiving In-Center Hemodialysis
  Active not recruiting · Phase 3 · Interventional · 353 enrolled · Akebia Therapeutics
  NCT06901505updated 2026-02-23
• Vadadustat for the Treatment of Nonintubated Acute Respiratory Distress Syndrome Due to Pathogen-Associated Lung Injury
  Recruiting · Phase 2 · Phase 3 · Interventional · 1,100 enrolled · Bentley J. Bobrow
  NCT07086755updated 2025-12-17

Frequently asked questions

How does Vadadustat work?

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).

What is Vadadustat used for?

According to FDA labeling, Vadadustat carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Vadadustat?

Vadadustat is classified as Other antianemic preparations, Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors, Organic Anion Transporter 3 Inhibitors, Transcription Factor Activity, Hemoglobin Function Restoration.

What are the brand names for Vadadustat?

Vadadustat is marketed under brand names including Vafseo.

What are the contraindications for Vadadustat?

Vadadustat labeling lists contraindications including: 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 )] .. Always consult the full prescribing information and a clinician.