Vadadustat

Vadadustat is a prescription medication indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for three or more months.

• Vadadustat is available under the following different brand names: Vafseo.

Common side effects of Vadadustat include:

• high blood pressure
• diarrhea

Serious side effects of Vadadustat include:

• liver problems include tiredness, pain in the right upper stomach area (abdomen), yellowing of the skin or the white part of the eyes, loss of appetite, dark urine
• high blood pressure
• seizures symptoms include headache, irritability, fear, confusion, or unusual feelings
• cancer
• gastrointestinal erosion symptoms include stomach-area (abdominal) discomfort or pain, nausea or vomiting, blood in vomit or stool, o black, tarry stools, trouble swallowing, pain in the throat or chest

Rare side effects of Vadadustat include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Anemia of chronic kidney disease

• Not being treated with an erythropoietin-stimulating agent (ESA)
  • Starting dose: 300 mg orally once a day
• Being switched from an ESA
  • Starting dose: 300 mg orally once a day
  • Owing to the gradual rise in hemoglobin (Hb) with Vadadustat, RBC transfusions or ESA treatment may be considered during the transition phase if Hb values fall below 9 g/dL or the Hb response is considered unacceptable
  • Patients receiving RBC transfusions should continue Vadadustat during the transfusion period
  • Pause Vadadustat for those patients receiving temporary ESA rescue treatment and resume when Hb levels greater than 10 g/dL
  • Depending on the ESA used for rescue, extend the pause in Vadadustat treatment to
    • 2 days after the last dose of epoetin
    • 7 days after the last dose of darbepoetin alfa
    • 14 days after the last dose of methoxy polyethylene glycol-epoetin beta
  • Following ESA rescue, resume Vadadustat at the previous dose or with a dose that is 150 mg greater than the prior dose, with subsequent titration
  • Dose titration and monitoring
  • Following Vadadustat initiation and after each dose adjustment, monitor Hb levels every 2 weeks until stable, then monitor at least monthly
  • Increase dose no more frequently than once every 4 weeks
  • Decreases in dose can occur more frequently
  • Adjust dose in 150-mg increments to achieve or maintain Hb levels within 10-11 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 responsiveness to Vadadustat
  • A single Hb excursion may not require a dosing change
    • If Hb rises rapidly (eg, above 1 g/dL in any 2 weeks or above 2 g/dL in 4 weeks), interrupt dosing or reduce the dose
    • If the Hb level above 11 g/dL, interrupt dosing until Hb is less than 11 g/dL; decrease dose by 150 mg from the previous dose
    • Do not continue for more than 24 weeks if a clinically meaningful increase in Hb level is not achieved
    • Alternative explanations for an inadequate response should be sought and treated before restarting therapy

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Vadadustat has severe interactions with no other drugs
• Vadadustat has serious interactions with no other drugs
• Vadadustat has moderate interactions with at least 88 other drugs
• Vadadustat has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Known hypersensitivity to Vadadustat or any of its components
• Uncontrolled hypertension

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Vadadustat?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Vadadustat?”

Cautions

• Increased risk of death, MI, stroke, VTE, and thrombosis of vascular access
  • Increased risk of arterial and venous thrombotic events (VTEs), that may be fatal, including myocardial infarction (MI), stroke, VTE, and vascular access thrombosis
  • Patients with cardiovascular (CV) or cerebrovascular disease are at increased risk of these events
  • Avoid use with a history of MI, cerebrovascular event, or acute coronary syndrome within the 3 months before initiating
  • Hb rise above 1 g/dL over 2 weeks may contribute to these risks
  • Hb above 11 g/dL is expected to further increase the risk of death and arterial and VTE, as occurs with ESAs, which also increase erythropoietin levels
  • No trial has identified an Hb target level, dose, or dosing strategy that does not increase these risks
  • Use the lowest dose sufficient to reduce the need for RBC transfusions
  • Adherence to dosing and Hb monitoring recommendations is important to avoid excessive erythropoiesis
  • Advise patients to seek immediate medical attention if they develop signs or symptoms of MI, stroke, VTE, or thrombosis of vascular access; evaluate and manage promptly if these occur
• Hepatotoxicity
  • May cause hepatotoxicity
  • The onset of hepatotoxicity generally occurs within the first 3 months of treatment
  • Measure ALT, AST, and bilirubin before initiating, monthly for the first 6 months, and then as clinically indicated
  • Discontinue if a patient has persistent ALT/AST above 3 x ULN or if ALT/AST elevations are accompanied by bilirubin above 2 x ULN
  • Not recommended in patients with cirrhosis or active, acute liver disease
• Hypertension
  • Contraindicated in patients with uncontrolled hypertension
  • Cases of hypertensive crisis, including hypertensive encephalopathy and seizures, have also been reported
  • Periodically monitor blood pressure and adjust or initiate antihypertensive therapy as needed
• Seizures
  • Seizures reported; monitor for premonitory neurologic symptoms
  • Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms, or changes in seizure frequency
• Gastrointestinal (GI) erosion
  • Serious GI erosions, including GI bleeding and the need for RBC transfusions, reported
  • Consider this risk, particularly in patients at increased risk for GI erosions (eg, history of GI erosion, peptic ulcer disease, use of concomitant medications that increase the risk of GI erosion, and current tobacco smokers and alcohol drinkers)
  • Advise patients of symptoms and signs of gastric and esophageal erosions and GI bleeding and to seek prompt medical care if these occur
  • Serious adverse reactions in patients with anemia due to CKD and not on dialysis
  • Safety has not been established for anemia due to CKD in adults not on dialysis and the use of Vadadustat is not recommended in this setting
  • In large clinical trials (PRO2TECT-1 and PRO2TECT-2), an increased risk of mortality, stroke, MI, serious acute kidney injury, serious hepatic injury, and serious GI erosions observed in patients treated with Vadadustat compared with darbepoetin alfa
• Malignancy
  • Because increased hypoxia-inducible factor (HIF)-1 levels may promote cancer growth, Vadadustat has not been studied and is not recommended in patients with active malignancies
  • No evidence of increased carcinogenicity was observed in animal studies
• Drug interaction overview
  • Iron supplements and phosphate binders
    • Modify the time of Vadadustat dosing
    • Coadministration with oral iron supplements, products containing iron, or phosphate binders decreases the exposure to Vadadustat
  • OAT1/OAT3 inhibitors
    • Monitor Hb response to Vadadustat
    • Coadministration with OAT1/OAT3 inhibitors may increase Vadadustat AUC
• BCRP substrates
  • Modify BCRP substrate dose according to product labeling
  • Vadadustat may increase the exposure of BCRP substrates
• Statins
  • Modify statin dose
  • Vadadustat increases peak plasma concentration and AUC of some statins (ie, simvastatin, rosuvastatin) when coadministered
• OAT3 substrates
  • Monitor
  • Vadadustat may increase exposure to coadministered OAT3 substrates

Pregnancy and Lactation

• Available data are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Clinical considerations
  • CKD in pregnancy increases risk for maternal hypertension, preeclampsia, miscarriage, stillbirth, preterm delivery, low birth weight infants, and polyhydramnios
• Lactation
  • Data are unavailable on the presence of Vadadustat in human milk, its effects on breastfed children, or its effects on milk production
  • Vadadustat is present in the milk of lactating rats; when a drug is present in animal milk, it is likely to be present in human milk
  • Given the serious adverse reactions seen in adults during treatment (eg, thrombotic vascular events), advise patients not to breastfeed during treatment and for 2 days after the final dose