Deferasirox

Administration

  • Type: Antidote
  • Dosage Forms: 125, 250, 500 mg disperse tab
  • Routes of Administration: Oral
  • Common Trade Names: Exjade

Adult Dosing

Iron toxicity, chronic transfusional

  • 20-30 mg/kg PO QD
    • Start: 20 mg/kg PO QD
    • Max: 40 mg/kg/day
    • Adjust dose by 5-10 mg/kg/day q3-6mo based on serum ferritin
    • Decrease dose 10 mg/kg/day if Cr >33% above baseline x2 weeks
    • Hold: Ferritin <500 mcg/L

Iron toxicity, chronic non-transfusion-dependent thalassemia-assoc.

  • 10-20 mg/kg PO QD
    • Start: 10 mg/kg PO QD
    • Max: 20 mg/kg/day
    • Decrease dose 50% if Cr >33% above baseline x2 weeks
      • Interrupt treatment if already at 5 mg/kg/day
    • Hold: Ferritin <300 mcg/L or liver iron <3 mg Fe/g

Pediatric Dosing

Iron toxicity, chronic transfusional

  • 2-15 yo
    • 20-30 mg/kg PO QD
      • Start: 20 mg/kg PO QD
      • Max: 40 mg/kg/day
      • Adjust dose by 5-10 mg/kg/day q3-6mo based on serum ferritin
      • Decrease dose 10 mg/kg/day if Cr >33% above baseline and >ULN
  • 16+ yo
    • 20-30 mg/kg PO QD
      • Start: 20 mg/kg PO QD
      • Max: 40 mg/kg/day
      • Adjust dose by 5-10 mg/kg/day q3-6mo based on serum ferritin
      • Decrease dose 10 mg/kg/day if Cr >33% above baseline x2 weeks

Iron toxicity, chronic non-transfusion-dependent thalassemia-assoc.

  • 10-15 yo
    • 10-20 mg/kg PO QD
      • Start: 10 mg/kg PO QD
      • Max: 20 mg/kg/day
      • Adjust dose based on serum ferritin trends and liver iron concentration
      • Decrease dose 5 mg/kg/day if Cr >33% above baseline and >ULN
  • 16+ yo
    • 10-20 mg/kg PO QD
      • Start: 10 mg/kg PO QD
      • Max: 20 mg/kg/day
      • Adjust dose based on serum ferritin trends and liver iron concentration
      • Decrease dose 50% if Cr >33% above baseline x2 weeks
        • Interrupt treatment if already at 5 mg/kg/day

Special Populations

  • Pregnancy Rating: C; Caution during pregnancy
  • Lactation risk: L3; Safety unknown

Renal Dosing

  • Adult:
    • CrCl 40-60: Decrease start dose 50%
    • Cr >2x ULN or CrCL <40: Contraindicated
  • Pediatric:
    • CrCl 40-60: Decrease start dose 50%
    • Cr >2x ULN or CrCL <40: Contraindicated

Hepatic Dosing

  • Adult:
    • Child-Pugh Class B: Decrease start dose 50%
    • Child-Pugh Class C: Avoid use
  • Pediatric:
    • Child-Pugh Class B: Decrease start dose 50%
    • Child-Pugh Class C: Avoid use

Contraindications

  • Allergy to class/drug
  • Cr >2x ULN or CrCl <40
  • Poor performance status
  • High risk myelodysplastic syndrome
  • Advanced malignancy
  • Thrombocytopenia <50,000
  • Hepatic impairment, Child-Pugh Class C
  • Caution if hepatic impairment, Child-Pugh Class A or B
  • Caution if renal impairment
  • Caution if concurrent nephrotoxic agent
  • Caution if hematologic disorder
  • Caution in patients >55yo

Adverse Reactions

Serious

Common

Pharmacology

  • Half-life: 8-16h
  • Metabolism: Liver; CYP450: minimal (8%); UGT: 1A1 (primary), 1A3 substrate
  • Excretion: Feces 84%, Urine 8%

Mechanism of Action

  • Chelates iron, promoting fecal iron excretion

Comments

  • Black Box Warning
    • Risk for renal failure in pts with comorbidities or advanced hematological disorder
    • Risk for hepatic failure in pts with Child-Pugh Class A, B, C disease
    • Risk for gastrointestinal Hemorrhage in elderly pts with advanced hematologic malignancies or low platelets

See Also

References