How is iron overload treated with Deseroxamine (Deferoxamine)?

Treatment of Iron Overload with Deferoxamine (Desferal)

Deferoxamine is the treatment of choice for iron overload in patients with secondary iron overload associated with ineffective erythropoiesis, particularly when phlebotomy is not feasible due to anemia. 1

Mechanism of Action and Indications

Deferoxamine is a hexadentate iron chelating molecule that:

• Binds with high affinity to the trivalent ferric ion in a 1:1 molar ratio
• Forms a soluble complex that is excreted primarily in the urine (60%) and feces (40%) 1
• Effectively removes iron from the reticuloendothelial system and various organs

Primary Indications:

• Secondary iron overload due to transfusion-dependent anemias (thalassemia, sickle cell disease)
• Acute iron intoxication
• Chronic iron overload when phlebotomy is contraindicated 2

Not Indicated For:

• Primary hemochromatosis (phlebotomy is preferred) 2
• Patients under 3 years with minimal iron overload 2

Administration Protocol

Standard Dosing Regimen:

• Dose: 40 mg/kg/day (typically not exceeding a total dose of 2g per 24 hours) 1
• Administration: Continuous subcutaneous infusion using a battery-operated pump
• Duration: 8-12 hours nightly
• Frequency: 5-7 nights weekly 1

Alternative Administration Routes:

• Intravenous: For patients with cardiac failure or requiring intensive chelation 1
• Intramuscular: Less effective than continuous infusion 2, 3

Monitoring Treatment Efficacy

Monitoring is more challenging in secondary iron overload compared to hereditary hemochromatosis:

• Serum ferritin may be misleading in secondary iron overload 1
• Monitoring options include:
  • Liver biopsy to assess hepatic iron concentration (HIC) 1
  • 24-hour urinary iron excretion measurements 1
  • MRI techniques to evaluate hepatic iron concentration non-invasively 1
  • T2* MRI for cardiac iron assessment 1

Clinical Benefits

• Reduces risk of clinical disease when hepatic iron concentration is reduced below 15,000 μg/g dry weight 1
• Improves cardiac function with significant improvements in left ventricular ejection fraction 1
• Reduces LV volume and LV mass index 1
• Prevents complications of iron overload in β-thalassemia 1

Limitations and Adverse Effects

Major Limitations:

• High maintenance cost
• Poor oral bioavailability necessitating parenteral administration
• Discomfort and inconvenience of administration
• Potential neurotoxicity 1

Common Adverse Effects:

• Local infusion site reactions (induration, erythema, swelling, itching) 1
• Flushing, urticaria, hypotension with rapid IV administration 2

Serious Adverse Effects:

• Increased susceptibility to Yersinia enterocolitica and Yersinia pseudotuberculosis infections 2
• Risk of mucormycosis (some cases fatal) 2
• Sensorineural deafness and visual disturbances 1
• Skeletal abnormalities and growth retardation 1
• Acute respiratory distress syndrome with high IV doses 2

Important Drug Interactions

• Vitamin C: Can enhance iron chelation but should be limited to 200 mg/day in adults, given in divided doses, and only started after one month of regular deferoxamine treatment 2
• Avoid high-dose vitamin C: Doses >500 mg/day have been associated with cardiac dysfunction when combined with deferoxamine 2
• Prochlorperazine: May lead to temporary impairment of consciousness 2

Patient Compliance Considerations

Patient compliance is a significant challenge with deferoxamine due to its administration route. Studies show:

• Significantly lower patient satisfaction compared to oral chelators like deferasirox 4
• Only 13.8% of patients on deferoxamine were willing to continue therapy compared to 85.8% on deferasirox 4
• For non-compliant patients with heavy iron overload, intermittent high-dose IV deferoxamine (15 mg/kg/hr for 48 hours every 2-4 weeks) has shown efficacy in reducing liver iron burden 5

Alternative Chelation Options

For patients unable to tolerate or comply with deferoxamine:

• Deferasirox: An oral iron chelator approved for treatment of secondary iron overload 1, 6
• Deferiprone: A bidentate oral chelator with good bioavailability but less consistent efficacy 1
• Combination therapy: Subcutaneous deferoxamine with oral deferiprone has shown improved efficacy in reducing myocardial iron and improving ejection fraction 1

Practical Clinical Algorithm

1. Assess iron overload severity:

   • Measure serum ferritin, transferrin saturation
   • Consider liver biopsy or MRI for hepatic iron concentration
   • T2* MRI for cardiac iron assessment if available

2. Determine if deferoxamine is appropriate:

   • Secondary iron overload present
   • Phlebotomy contraindicated (anemia, hemodynamic instability)
   • Patient age >3 years with significant iron burden

3. Initiate standard therapy:

   • 40 mg/kg/day via subcutaneous pump infusion over 8-12 hours
   • 5-7 nights weekly

4. Monitor for efficacy:

   • Periodic assessment of iron parameters
   • Consider repeat imaging to assess organ iron content
   • Monitor for complications of iron overload

5. Address compliance issues:

   • Consider alternative administration routes if needed
   • Evaluate for potential switch to oral chelators if compliance is poor
   • Consider combination therapy for severe cases