What is the oral dose of deferoxamine for pediatric patients with iron overload?

Deferoxamine for Pediatric Iron Overload

Deferoxamine is not available in oral form for pediatric patients with iron overload; it must be administered parenterally (subcutaneously or intravenously) at doses of 20-50 mg/kg/day.

Administration Routes and Dosing

• Deferoxamine is a hexadentate iron chelator that must be administered parenterally as it is not effectively absorbed by the gastrointestinal tract 1
• The typical chronic dosing range for deferoxamine in pediatric patients is 20-50 mg/kg/day 1
• For subcutaneous administration, deferoxamine is typically given as a 10% solution via a small portable pump as an 8-14 hour infusion for 5-7 days per week 1
• For patients with severe cardiac iron overload, continuous intravenous infusion may be preferred as it clears cardiac iron at a faster rate (nearly 5% per month) compared to intermittent subcutaneous infusions (1.1-2.2% per month) 1
• Weekend very high-dose intravenous deferoxamine (15 mg/kg/hour over 48 hours every 2-4 weeks) has been reported as an effective alternative regimen for pediatric patients 2

Clinical Indications

• Deferoxamine is indicated as a second-line therapy when phlebotomy is not feasible or cannot be performed at the desired frequency 1
• Specific indications include patients with:
  • Inaccessible veins or needle phobia 1
  • Concomitant anemia 1
  • Life-threatening cardiac iron overload (particularly in juvenile hemochromatosis) 1
  • Conditions where bloodletting can be harmful 1
• In patients with advanced disease who poorly tolerate phlebotomies, personalized mini-phlebotomies plus subcutaneous infusion of deferoxamine could be considered 1

Efficacy and Monitoring

• Deferoxamine has been shown to be effective in removing excess iron in pediatric patients with transfusional iron overload 3
• Regular monitoring is essential during deferoxamine therapy:
  • Iron status (ferritin and hemoglobin) should be monitored to prevent both iron deficiency and iron overload 1
  • Ophthalmologic and audiological tests are recommended due to potential sensory toxicity 1
  • Growth monitoring is important, especially in younger children 1

Adverse Effects and Precautions

• Common adverse effects include local infusion-site reactions (induration, erythema, swelling, and itching) 1
• More serious adverse events can occur, particularly with higher doses relative to iron burden 1:
  • Sensorineural deafness
  • Visual disturbances
  • Skeletal abnormalities
  • Growth retardation
• Increased risk of Yersinia and Klebsiella infections has been reported in patients treated with deferoxamine 1
• Renal toxicity and acute respiratory distress syndrome have been described, particularly after excessively high intravenous doses 1
• All iron chelation drugs are contraindicated in pregnancy, and dose adjustment is required in renal failure 1

Alternative Oral Chelators

• Since deferoxamine is not available orally, two oral alternatives exist for pediatric patients:
  • Deferiprone (75-100 mg/kg/day divided into 3 doses) 1
  • Deferasirox (10-15 mg/kg/day starting dose for hemochromatosis patients) 1
• Deferasirox has been the most studied oral chelator in hemochromatosis and may be considered when deferoxamine is contraindicated or inadequate 1
• For severe cardiac iron overload in juvenile hemochromatosis, combination therapy with oral deferiprone and intravenous deferoxamine has been described in case reports 1

Practical Considerations

• The parenteral administration of deferoxamine can be cumbersome, which may adversely affect adherence to treatment 1
• For patients with severe cardiac iron overload, continuous administration provides better outcomes as labile iron rebounds quickly after discontinuation of chelation therapy 1
• Patients requiring deferoxamine therapy should be referred to specialized centers for evaluation and treatment 1