By using PrescriberAI, you agree to the AI Terms of Use.
Vafseo Prescribing Information
VAFSEO increases the risk of arterial and venous thrombotic events, that may be fatal, including myocardial infarction, stroke, venous thromboembolism and vascular access thrombosis
A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks. Targeting a hemoglobin level of greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with 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 transfusions. Adherence to dosing and hemoglobin monitoring recommendations is important to avoid excessive erythropoiesis
Advise patients to seek immediate medical attention if they develop signs or symptoms of myocardial infarction, stroke, venous thromboembolism, or thrombosis of vascular access. Evaluate and manage promptly if these occur.
VAFSEO increases the risk of arterial and venous thrombotic events, that may be fatal, including myocardial infarction, stroke, venous thromboembolism and vascular access thrombosis
A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks. Targeting a hemoglobin level of greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with 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 transfusions. Adherence to dosing and hemoglobin monitoring recommendations is important to avoid excessive erythropoiesis
Advise patients to seek immediate medical attention if they develop signs or symptoms of myocardial infarction, stroke, venous thromboembolism, or thrombosis of vascular access. Evaluate and manage promptly if these occur.
Following initiation of therapy and after each dose adjustment, monitor hemoglobin (Hb) levels, every two weeks until stable, then monitor at least 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 Hb levels within 10 g/dL to 11 g/dL. Doses may range from 150 mg to a maximum of 600 mg. When adjusting the dose, consider the patient’s Hb variability, Hb rate of rise and rate of decline, and VAFSEO responsiveness. A single Hb excursion may not require a dosing change.
- If the Hb rises rapidly (e.g., more than 1 g/dL in any 2-week period or more than 2 g/dL in 4 weeks), interrupt or reduce the dose.
- If the Hb level exceeds 11 g/dL, interrupt the dose of VAFSEO until Hb is less than or equal to 11 g/dL then resume with a dose that is 150 mg less than the dose prior to interruption.
- Treatment with VAFSEO should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in Hb level is not achieved. Alternative explanations for an inadequate response should be sought and treated before re-starting therapy.
Following initiation of therapy and after each dose adjustment, monitor hemoglobin (Hb) levels, every two weeks until stable, then monitor at least 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 Hb levels within 10 g/dL to 11 g/dL. Doses may range from 150 mg to a maximum of 600 mg. When adjusting the dose, consider the patient’s Hb variability, Hb rate of rise and rate of decline, and VAFSEO responsiveness. A single Hb excursion may not require a dosing change.
- If the Hb rises rapidly (e.g., more than 1 g/dL in any 2-week period or more than 2 g/dL in 4 weeks), interrupt or reduce the dose.
- If the Hb level exceeds 11 g/dL, interrupt the dose of VAFSEO until Hb is less than or equal to 11 g/dL then resume with a dose that is 150 mg less than the dose prior to interruption.
- Treatment with VAFSEO should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in Hb level is not achieved. Alternative explanations for an inadequate response should be sought and treated before re-starting therapy.
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.
- 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 Serious Adverse Reactions in Patients with Anemia Due to Chronic Kidney Disease and Not on DialysisThe safety of VAFSEO has not been established for the treatment of anemia due to CKD in adults not on dialysis and its use is not recommended in this setting
[see Indications and Usage ].In large clinical trials in adults with anemia of CKD who were not on dialysis (PRO2TECT-1 and PRO2TECT-2), an increased risk of mortality, stroke, myocardial infarction, serious acute kidney injury, serious hepatic injury, and serious gastrointestinal erosions was observed in patients treated with VAFSEO compared to darbepoetin alfa.
VAFSEO is available as a film-coated, immediate-release tablet in the following strengths:
Tablet Strength | Tablet Shape/Color | Tablet Markings |
| 150 mg | round/white | “VDT” and “150” |
| 300 mg | oval/yellow | “VDT” and “300” |
| 450 mg | oval/pink | “VDT” and “450” |
VAFSEO is contraindicated in patients:
- with a known hypersensitivity to VAFSEO or any of its components [see Description (.)]
11 DESCRIPTIONVAFSEO contains vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor. Vadadustat is 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid. Vadadustat has a molecular weight of 306.70. The empirical formula is C14H11ClN2O4.
The chemical structure is:
Vadadustat is a white to off-white solid that is practically insoluble in water.
Vadadustat is formulated as a film-coated, immediate-release tablet for oral administration.
VAFSEO is available in 150 mg, 300 mg and 450 mg strengths. Inactive ingredients include: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablet film-coating contains polyvinyl alcohol, polyethylene glycol (PEG) and talc.
Colorants include:
150 mg tablet - titanium dioxide
300 mg tablet - titanium dioxide and yellow iron oxide
450 mg tablet - titanium dioxide, iron oxide red and ferrosoferric oxideChemical structure - with uncontrolled hypertension [see Warnings and Precautions (.)]
5.3 HypertensionVAFSEO is contraindicated in patients with uncontrolled hypertension. In the INNO2VATE-1 and INNO2VATE-2 clinical trials, worsening of hypertension was reported in 14% (9.4 per 100 person-years [PY]) of patients receiving VAFSEO and 17% (11.8 per 100 PY) of patients receiving darbepoetin alfa. Serious worsening of hypertension was reported in 2.7% (1.7 per 100 PY) of patients receiving VAFSEO and 3% (1.8 per 100 PY) of patients receiving darbepoetin alfa. Cases of hypertensive crisis including hypertensive encephalopathy and seizures have also been reported in patients receiving VAFSEO. Periodically monitor blood pressure and adjust or initiate anti-hypertensive therapy as needed.
The following clinically significant adverse reactions are discussed elsewhere in the labeling:
- Increased risk of death, myocardial infarction, stroke and venous thromboembolism, and thrombosis of vascular access [seeand Warnings and Precautions
WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, AND THROMBOSIS OF VASCULAR ACCESSVAFSEO increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE)[see Warnings and Precautions ].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 ].No trial has identified a hemoglobin target level, dose of VAFSEO, or dosing strategy that does not increase these risks[see Dosage and Administration ].Use the lowest dose of VAFSEO sufficient to reduce the need for red blood cell transfusions [see Dosage and Administration ].WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS.See full prescribing information for complete boxed 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 transfusions.
]5.1 Increased Risk of Death, Myocardial Infarction (MI), Stroke, Venous Thromboembolism, and Thrombosis of Vascular AccessVAFSEO 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 ]. 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. Targeting a hemoglobin level of greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with 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 transfusions. Adherence to dosing and hemoglobin monitoring recommendations is important to avoid excessive erythropoiesis
[see Dosage and Administration ].Advise patients to seek immediate medical attention if they develop signs or symptoms of myocardial infarction, stroke, venous thromboembolism, or thrombosis of vascular access. Evaluate and manage promptly if these occur.
- Hepatotoxicity [see Warnings and Precautions ()]
5.2 HepatotoxicityVAFSEO may cause hepatotoxicity. In clinical trials, hepatocellular injury attributed to VAFSEO was reported in less than 1% of patients, including one case of severe hepatocellular injury with jaundice. All events were asymptomatic and resolved after discontinuation of VAFSEO. The time to onset was generally within the first 3 months of treatment.
Elevated serum ALT, AST, and bilirubin were seen in 1.8%, 1.8% and 0.3% of CKD patients treated with VAFSEO, respectively.
Measure ALT, 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 Dosage and Administration ].Discontinue VAFSEO if there is persistent ALT or AST greater than 3 times ULN or if ALT or AST elevations greater than 3 times upper limit of normal (ULN) are accompanied by a bilirubin increase greater than 2 times ULN.
VAFSEO is not recommended in patients with cirrhosis or active, acute liver disease.
- Hypertension [see Warnings and Precautions ()]
5.3 HypertensionVAFSEO is contraindicated in patients with uncontrolled hypertension. In the INNO2VATE-1 and INNO2VATE-2 clinical trials, worsening of hypertension was reported in 14% (9.4 per 100 person-years [PY]) of patients receiving VAFSEO and 17% (11.8 per 100 PY) of patients receiving darbepoetin alfa. Serious worsening of hypertension was reported in 2.7% (1.7 per 100 PY) of patients receiving VAFSEO and 3% (1.8 per 100 PY) of patients receiving darbepoetin alfa. Cases of hypertensive crisis including hypertensive encephalopathy and seizures have also been reported in patients receiving VAFSEO. Periodically monitor blood pressure and adjust or initiate anti-hypertensive therapy as needed.
- Seizures [see Warnings and Precautions ()]
5.4 SeizuresSeizures have occurred in patients treated with VAFSEO. In the INNO2VATE-1 and INNO2VATE-2 clinical trials, seizures occurred in 1.6% (1.0 per 100 PY) of patients who received VAFSEO and 1.6% (1.0 per 100 PY) of patients who received darbepoetin alfa. Following initiation of VAFSEO, monitor patients closely for premonitory neurologic symptoms. Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms, or change in seizure frequency.
- Gastrointestinal erosion [see Warnings and Precautions ()]
5.5 Gastrointestinal ErosionIn the INNO2VATE-1 and INNO2VATE-2 clinical trials, gastric or esophageal erosions occurred in 6.4% (4.0 per 100 PY) of patients receiving VAFSEO and 5.3% (3.3 per 100 PY) of darbepoetin alfa-treated patients. Serious gastrointestinal erosions, including gastrointestinal bleeding and the need for red blood cell transfusions were reported in 3.4% (2.1 per 100 PY) and 3.3% (2.0 per 100 PY) of those receiving VAFSEO and darbepoetin alfa, respectively. Consider this risk particularly in patients at increased risk for gastrointestinal erosions, such as those with a history of gastrointestinal erosion, peptic ulcer disease, use of concomitant medications that increase the risk of gastrointestinal erosion, and current tobacco smokers and alcohol drinkers.
Advise patients of the symptoms and signs of gastric and esophageal erosions and of gastrointestinal bleeding and to seek prompt medical care if these occur.
- Serious adverse reactions in patients with anemia due to chronic kidney disease and not on dialysis [see Warnings and Precautions ()]
5.6 Serious Adverse Reactions in Patients with Anemia Due to Chronic Kidney Disease and Not on DialysisThe safety of VAFSEO has not been established for the treatment of anemia due to CKD in adults not on dialysis and its use is not recommended in this setting
[see Indications and Usage ].In large clinical trials in adults with anemia of CKD who were not on dialysis (PRO2TECT-1 and PRO2TECT-2), an increased risk of mortality, stroke, myocardial infarction, serious acute kidney injury, serious hepatic injury, and serious gastrointestinal erosions was observed in patients treated with VAFSEO compared to darbepoetin alfa.
VAFSEO contains vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor. Vadadustat is 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid. Vadadustat has a molecular weight of 306.70. The empirical formula is C14H11ClN2O4.
The chemical structure is:
Vadadustat is a white to off-white solid that is practically insoluble in water.
Vadadustat is formulated as a film-coated, immediate-release tablet for oral administration.
VAFSEO is available in 150 mg, 300 mg and 450 mg strengths. Inactive ingredients include: colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablet film-coating contains polyvinyl alcohol, polyethylene glycol (PEG) and talc.
Colorants include:
150 mg tablet - titanium dioxide
300 mg tablet - titanium dioxide and yellow iron oxide
450 mg tablet - titanium dioxide, iron oxide red and ferrosoferric oxide