LuciVadadu (Vadadustat)

About  Vadadustat

Vadadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor.

Anemia of Chronic Kidney Disease

Indicated for treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for ≥3 months

Not being treated with an erythropoietin-stimulating agent (ESA)

• Starting dose: 300 mg PO qDay

Being switched from an ESA

• Starting dose: 300 mg PO qDay
• Owing to the gradual rise in hemoglobin (Hb) with vadadustat, RBC transfusions or ESA treatment may be considered during transition phase if Hb values fall to <9 g/dL or 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 ≥10 g/dL

• Depending on ESA used for rescue, extend pause in vadadustat treatment to

  • 2 days after last dose of epoetin
  • 7 days after last dose of darbepoetin alfa
  • 14 days after last dose of methoxy polyethylene glycol-epoetin beta
• Following ESA rescue, resume vadadustat at 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 q2Weeks until stable, then monitor at least monthly
• Increase dose no more frequently than once q4Weeks
• 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 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, >1 g/dL in any 2-week period or >2 g/dL in 4 weeks), interrupt dosing or reduce dose
  • If Hb level >11 g/dL, interrupt dosing until Hb is ≤11 g/dL; decrease dose by 150 mg from previous dose
  • Do not continue >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 Modifications

Oral iron and phosphate binders

• Administer vadadustat ≥1 hr before oral iron supplements, products containing iron, or iron-containing phosphate binders
• Administer vadadustat ≥1 hr before or ≥2 hr after non-iron-containing phosphate binders

Renal impairment

• Can be administered without regard to the timing or type of dialysis

Hepatic impairment

• Mild-to-moderate (Child-Pugh A or B): No significant differences in pharmacokinetics
• Severe (Child-Pugh C): Not studied
• Not recommended for patients with cirrhosis or active, acute liver disease