Version July 2025
Vadadustat 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 vadadustat, or dosing strategy that does not increase these risks. Use the lowest dose of vadadustat sufficient to reduce the need for red blood cell transfusions.
Dosage guidance:
Clinical considerations: Correct and exclude other causes of anemia (eg, vitamin deficiencies, metabolic or chronic inflammatory conditions, bleeding) prior to therapy. Ensure adequate iron stores before initiating and throughout therapy. The manufacturer recommends supplemental iron be administered if serum ferritin is <100 ng/mL or serum transferrin saturation is <20%; however, the threshold for iron replacement should be individualized based on clinical considerations (eg, trends in Hb level, goals of therapy) (Ref). Most patients with chronic kidney disease will require iron supplementation during the course of therapy.
Anemia due to chronic kidney disease (dialysis-dependent):
Patients not receiving an erythropoietin-stimulating agent: Initial: Oral: 300 mg once daily.
Patients being switched from an erythropoietin-stimulating agent: Initial: Oral: 300 mg once daily. Note: During transition phase, if Hb falls to <9 g/dL or Hb response is unacceptable, may consider RBC transfusions or erythropoietin-stimulating agent treatment.
If patient receives RBC transfusions: Continue vadadustat treatment.
If patient receives erythropoietin-stimulating agent rescue treatment: Hold vadadustat treatment until Hb levels are ≥10 g/dL. Hold vadadustat until 2 days after last epoetin dose, 7 days after last darbepoetin alfa dose, or 14 days after last methoxy polyethylene glycol-epoetin beta dose. When reinitiating vadadustat, resume at previous dose or increase previous dose by 150 mg.
Dosage adjustment: Use the lowest maintenance dose necessary to reduce the need for RBC transfusions and manage symptoms (Ref). Do not increase the dose more often than once every 4 weeks but may decrease the dose more frequently. Adjust daily dose in increments of 150 mg (range: 150 mg/day to maximum dose of 600 mg/day). Target Hb range suggested by Kidney Disease: Improving Global Outcomes (KDIGO) is 10 to 11.5 g/dL, while manufacturer's labeling recommends a range of 10 to 11 g/dL.
If the Hb increases >1 g/dL in any 2-week period or >2 g/dL in 4 weeks: Hold or decrease the dose.
If the Hb increases to >11 g/dL: Hold the dose until Hb is ≤11 g/dL. Restart at a dose 150 mg less than the previous dose.
Lack of Hb response: Discontinue treatment after 24 weeks (or sooner) if no meaningful Hb increase is achieved; avoid repeated dose escalations without Hb improvement. Identify and treat underlying causes of inadequate response before restarting therapy (Ref).
Missed doses: If a dose is missed, administer as soon as possible on the same day and then return to the normal schedule the following day. Do not take 2 doses on the same day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Not indicated for use in patients with chronic kidney disease not receiving dialysis.
Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (16%): No dosage adjustment necessary (indicated for use in this population). May be administered without regard to dialysis timing.
Peritoneal dialysis: No dosage adjustment necessary (indicated for use in this population).
Hepatic impairment prior to treatment initiation: Not recommended in patients with cirrhosis or active, acute liver disease.
Acute hepatotoxicity during treatment: Discontinue if there is persistent ALT or AST >3 times ULN or if ALT or AST >3 times ULN plus bilirubin >2 times ULN.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (14%; including hypertensive crisis, hypertensive encephalopathy)
Gastrointestinal: Diarrhea (13%)
1% to 10%:
Cardiovascular: Arteriovenous fistula-site complication (thrombosis: 6%)
Gastrointestinal: Abdominal pain (7%), gastrointestinal erosion (6%; including gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer), nausea (8%), vomiting (7%; including hematemesis)
Hematologic & oncologic: Malignant neoplasm (2%)
Hepatic: Increased serum alanine aminotransferase (2%), increased serum aspartate aminotransferase (2%)
Nervous system: Dizziness (6%), fatigue (8%), headache (9%), seizure (2%)
Respiratory: Dyspnea (6%)
<1%: Hepatic: Hepatotoxicity, increased serum bilirubin
Frequency not defined:
Cardiovascular: Acute myocardial infarction, arterial thrombosis, deep vein thrombosis, pulmonary embolism, shunt thrombosis, venous thromboembolism
Nervous system: Cerebrovascular accident
Hypersensitivity to vadadustat or any component of the formulation; uncontrolled hypertension.
Concerns related to adverse effects:
• GI effects: Use caution in patients with a history of GI erosions or peptic ulcer disease. GI erosions and bleeding were reported in clinical trials. Taking medications associated with GI erosions, smoking tobacco, and drinking alcohol may increase risk.
• Hepatic effects: Avoid use in patients with acute liver disease or cirrhosis due to the risk of hepatotoxicity. Increases in serum liver aminotransferases and bilirubin were reported.
• Hypertension: Use caution in patients with hypertension; contraindicated in patients with uncontrolled hypertension. Worsening of hypertension, including hypertensive crisis, has been reported.
• Neurologic effects: Use caution in patients with a history of seizures. Seizures were reported in clinical trials, including new-onset seizures.
• Thrombotic vascular events: May increase the risk of thrombotic vascular events (eg, acute myocardial infarction [MI], stroke, venous thromboembolism, vascular access thrombosis), which may be fatal. A rapid rise in Hb (>1 g/dL over 2 weeks) may contribute to these risks.
Disease-related concerns:
• Cardiovascular or cerebrovascular disease: Avoid use in patients with a history of MI, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting vadadustat due to increased risk for thrombotic vascular events.
• Chronic kidney disease (patients not on dialysis): Not recommended in patients with chronic kidney disease not on dialysis. Increased risk of mortality, stroke, MI, acute kidney injury, hepatic injury, and GI erosions were reported.
• Malignancy: Not recommended in patients with active malignancies. Cancer growth may be affected by increased hypoxia-inducible factor-1 levels.
Other warnings/precautions:
• Abuse: Intentional nontherapeutic use of vadadustat may be seen in athletes due to its effects on erythropoiesis. Misuse by healthy persons may lead to polycythemia, which can lead to life-threatening cardiovascular events (eg, stroke, MI, thromboembolism).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Vafseo: 150 mg, 300 mg
No
Tablets (Vafseo Oral)
150 mg (per each): $25.56
300 mg (per each): $51.12
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Swallow tablet whole; do not cut, crush, or chew. May be administered with or without food. Administer ≥1 hour before iron-containing products. Administer ≥1 hour before or 2 hours after phosphate binders that do not contain iron.
Anemia due to chronic kidney disease (dialysis-dependent): Treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for ≥3 months.
Limitations of use: Has not been shown to improve quality of life, fatigue, or patient well-being; not indicated as a substitute for RBC transfusions in patients who require immediate correction of anemia or treatment of anemia of CKD in patients who are not on dialysis.
Vadadustat may be confused with daprodustat, febuxostat.
Substrate of OAT1/3; Inhibits BCRP, OAT1/3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider Therapy Modification
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Vadadustat may increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Cefaclor: Vadadustat may increase serum concentration of Cefaclor. Risk C: Monitor
Ceftizoxime: Vadadustat may increase serum concentration of Ceftizoxime. Risk C: Monitor
Cladribine: BCRP/ABCG2 Inhibitors may increase serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider Therapy Modification
Darbepoetin Alfa: Vadadustat may increase adverse/toxic effects of Darbepoetin Alfa. Management: For adult patients treated with vadadustat who require temporary darbepoetin alfa rescue therapy, interrupt vadadustat treatment during darbepoetin alfa therapy. Do not restart vadadustat until 7 days after the last darbepoetin alfa dose. Risk X: Avoid
Erythropoiesis-Stimulating Agents: Vadadustat may increase adverse/toxic effects of Erythropoiesis-Stimulating Agents. Management: For adult patients treated with vadadustat who require temporary erythropoiesis-stimulating agent (ESA) rescue therapy, interrupt vadadustat treatment during ESA therapy. Do not restart vadadustat until 2 days after the last epoetin dose. Risk X: Avoid
Famotidine: Vadadustat may increase serum concentration of Famotidine. Risk C: Monitor
Fexinidazole: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider Therapy Modification
HMG-CoA Reductase Inhibitors (Statins): Vadadustat may increase serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Iron Preparations: May decrease serum concentration of Vadadustat. Management: Administer vadadustat at least 1 hour before oral iron supplements. Risk D: Consider Therapy Modification
Ketoprofen: Vadadustat may increase serum concentration of Ketoprofen. Ketoprofen may increase serum concentration of Vadadustat. Risk C: Monitor
Leflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Methoxy Polyethylene Glycol-Epoetin Beta: Vadadustat may increase adverse/toxic effects of Methoxy Polyethylene Glycol-Epoetin Beta. Management: For patients treated with vadadustat who require temporary methoxy polyethylene glycol-epoetin beta rescue therapy, interrupt vadadustat treatment and do not restart vadadustat until 14 days after the last methoxy polyethylene glycol-epoetin beta dose. Risk X: Avoid
Nitisinone: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
OAT1/3 Inhibitors: May increase serum concentration of Vadadustat. Risk C: Monitor
OAT1/3 Substrates (Clinically Relevant): Vadadustat may increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
PAZOPanib: BCRP/ABCG2 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Penicillin G (Parenteral/Aqueous): Vadadustat may increase serum concentration of Penicillin G (Parenteral/Aqueous). Risk C: Monitor
Penicillin G Benzathine: Vadadustat may increase serum concentration of Penicillin G Benzathine. Risk C: Monitor
Penicillin G Procaine: Vadadustat may increase serum concentration of Penicillin G Procaine. Risk C: Monitor
Phosphate Binders: May decrease serum concentration of Vadadustat. Management: Administer vadadustat at least 1 hour before or 2 hours after phosphate binders. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Rosuvastatin: Vadadustat may increase serum concentration of Rosuvastatin. Management: Do not exceed rosuvastatin doses of 5 mg daily and monitor for rosuvastatin adverse effects (eg, myopathy) during coadministration with vadadustat. Risk D: Consider Therapy Modification
Seladelpar: OAT1/3 Inhibitors may increase serum concentration of Seladelpar. Risk X: Avoid
Simvastatin: Vadadustat may increase serum concentration of Simvastatin. Management: Initiate simvastatin at 5 mg daily and no not exceed 20 mg daily during coadministration with vadadustat. Monitor patients for simvastatin adverse effects (eg, myopathy) during any combined use. Risk D: Consider Therapy Modification
SITagliptin: Vadadustat may increase hypoglycemic effects of SITagliptin. Risk C: Monitor
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sucroferric Oxyhydroxide: May decrease serum concentration of Vadadustat. Management: Administer vadadustat at least 1 hour before oral sucroferric oxyhydroxide. Risk D: Consider Therapy Modification
Sulopenem Etzadroxil: OAT1/3 Inhibitors may increase serum concentration of Sulopenem Etzadroxil. Risk C: Monitor
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Taurursodiol: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid
Teriflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Ubrogepant: BCRP/ABCG2 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider Therapy Modification
Vaborbactam: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
In animal reproduction studies, maternal toxicity and adverse fetal events were observed in some studies with oral doses equivalent to 1.7 and 1.5 times the maximum recommended human dose (based on AUC) in rats and rabbits, respectively.
It is not known if vadadustat is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 2 days after the last vadadustat dose.
Following initiation of therapy and after each dose adjustment, monitor Hb levels every 2 weeks until stable, then at least monthly. Evaluate iron status (eg, serum ferritin, serum transferrin saturation) before and during treatment. Monitor ALT/AST and bilirubin (baseline, repeat monthly for first 6 months, then as clinically indicated). Periodically monitor BP. Monitor patients closely for premonitory neurologic symptoms.
Vadadustat reversibly inhibits hypoxia-inducible factor prolyl hydroxylase-1 (PH1), PH2, and PH3, which stimulates transcription of the erythropoietin gene in the kidneys and liver, leading to increased levels of endogenous erythropoietin.
Protein binding: ≥99.5%.
Metabolism: Hepatic primarily via glucuronidation by UDP-glucuronosyltransferase (UGT) enzymes.
Half-life elimination: 9.2 hours (in patients on chronic hemodialysis).
Time to peak: ~2 to 3 hours.
Excretion: Urine: 58.9% (<1% as unchanged drug); feces: 26.9% (9% as unchanged drug).
