Vadadustat

FDA label

Read the full label on DailyMed ↗

Titration Increase dose no more frequently than once every 4 weeks (decreases may occur more frequently)

Renal Indicated in dialysis-dependent CKD; may be given without regard to timing or type of dialysis. Not recommended in CKD not on dialysis (increased mortality, stroke, MI, kidney/hepatic injury observed)

Hepatic Not recommended in cirrhosis or active, acute liver disease

If Hb >11 g/dL: interrupt until Hb <=11, resume 150 mg lower. If Hb rises >1 g/dL in 2 weeks or >2 g/dL in 4 weeks: interrupt or reduce dose.

Instructions

• Swallow whole; do not cut, crush, or chew; with or without food
• Take at least 1 h before oral iron, iron-containing products, or iron-containing phosphate binders; at least 1 h before or 2 h after non-iron phosphate binders
• Missed dose: take ASAP unless same day as next dose - then skip; do not double
• Correct/exclude other causes of anemia before starting; give supplemental iron if ferritin <100 mcg/L or TSAT <20%
• Measure ALT, AST, bilirubin before initiation and monthly for first 6 months; discontinue if persistent ALT/AST >3x ULN or ALT/AST >3x ULN with bilirubin >2x ULN
• Monitor Hb q2 weeks after initiation or dose change until stable, then at least monthly
• Switching from ESA: start 300 mg QD; if ESA rescue is needed, pause vadadustat and resume (Hb >=10 g/dL) 2 days after last epoetin, 7 days after darbepoetin alfa, 14 days after methoxy PEG-epoetin beta
• Discontinue if no clinically meaningful Hb increase by 24 weeks

Contraindications

• Uncontrolled hypertension

Cautions

• Thrombotic vascular events incl. MACE (boxed): avoid if MI, cerebrovascular event, or ACS within prior 3 months
• Hepatotoxicity: monitor LFTs; not recommended in cirrhosis or active acute liver disease
• Worsening hypertension incl. hypertensive crisis: monitor BP, adjust antihypertensives
• Seizures: monitor for new-onset seizures, premonitory symptoms, or change in frequency
• GI erosion and GI bleeding: higher risk with prior erosion/PUD, erosion-risk comedications, smoking, alcohol
• Not recommended with active malignancy (HIF-mediated tumor-growth concern)
• Not recommended in CKD not on dialysis (increased mortality, stroke, MI, serious AKI, hepatic injury, GI erosions vs darbepoetin)

Adverse reactions

• Hypertension (14%) and diarrhea (13%) most common (>=10%)
• Headache, nausea, fatigue, abdominal pain, vomiting, GI erosion, dizziness, dyspnea, AV fistula thrombosis, dialysis-related complication (5-9%)
• Thrombotic vascular events: vascular access thrombosis, MI, stroke, DVT, PE

Pregnancy Insufficient human data; reduced fetal weight in animals at maternally toxic doses; use only if benefit justifies fetal risk (exposure registry 1-844-445-3799)

Lactation Do not breastfeed during treatment and for 2 days after final dose