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

• Nephrotoxicity
• Hepatotoxicity
• GI hemorrhage
• GI perforation
• GI ulcer
• Agranulocytosis
• Neutropenia
• Thrombocytopenia
• Anemia exacerbation
• Hearing loss
• Cataracts
• Lens opacification
• Retinal disorders
• Hypersensitivity reaction
• Anaphylaxis
• SJS
• Erythema multiforme
• Leukocytoclastic vasculitis

Common

• Cr elevated
• Abdominal pain
• Proteinuria, intermittent
• Diarrhea
• Nausea/Vomiting
• Rash
• ALT elevated
• IOP elevated

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

• Iron toxicity

References

Authors

Jonathan Warren