Is a combination of asunaprevir (ASV) with deferiprone (DFP) recommended for managing severe iron overload with significantly elevated ferritin levels?

Management of Severe Iron Overload with Ferritin Increase from 1000 to 4000

Combination therapy with deferiprone (DFP) is strongly recommended for managing severe iron overload with significantly elevated ferritin levels from 1000 to 4000, as this combination approach is more effective than monotherapy for reducing iron stores to normal range levels. 1

Assessment of Iron Overload

• A ferritin increase from 1000 to 4000 ng/mL indicates severe iron overload requiring prompt intervention to prevent organ damage 2
• Transferrin saturation should be measured to better assess iron status and confirm iron overload 3
• Monitoring of cardiac and liver function is essential as these are primary target organs for iron toxicity 2

Treatment Recommendations

First-line Approach:

• Combination therapy with deferiprone (75-100 mg/kg/day) plus deferoxamine (40-60 mg/kg at least 3 days per week) is the most effective regimen for rapidly reducing iron stores to normal levels 1
• This combination has been shown to normalize iron levels within one year in some cases 1
• The combination approach is particularly effective for improving cardiac iron removal, which is critical as cardiac complications are the leading cause of death in iron overload 4, 1

Maintenance Therapy:

• Once iron levels normalize (ferritin <1000 ng/mL), deferiprone monotherapy (80-100 mg/kg/day) can effectively maintain normal iron levels in most patients 1
• Chelation therapy should continue as long as the patient requires transfusions and iron overload remains clinically relevant 2

Monitoring During Treatment

• Monitor serum ferritin levels at intervals commensurate with transfusion frequency, at minimum every 3 months, monthly if possible 2
• Regular cardiac and liver MRI T2* assessments are recommended to evaluate organ-specific iron deposition 1
• Monitor complete blood counts weekly during deferiprone therapy due to risk of agranulocytosis 5, 6
• Evaluate liver and renal function regularly during treatment 4

Benefits of Combination Therapy

• Combination therapy with deferiprone and deferoxamine has shown superior efficacy in:
  • Reducing serum ferritin to normal range levels 1
  • Improving cardiac T2* MRI measurements (indicating reduced cardiac iron) 1
  • Improving left ventricular ejection fraction compared to monotherapy 4
  • Achieving negative iron balance more effectively than either agent alone 7

Potential Adverse Effects to Monitor

• Deferiprone-related adverse events include:
  • Agranulocytosis (0.6% of patients) - requires weekly monitoring of white cell counts 5
  • Joint pain and arthropathy (15%) 5, 7
  • Gastrointestinal disturbances (6%) 5, 7
  • Zinc deficiency (1%) 5, 7
• Deferoxamine-related adverse events include:
  • Local reactions at infusion sites including pain and swelling 4
  • Visual and auditory disturbances with long-term use 4

Important Considerations

• The choice of chelation therapy should consider the severity of iron overload, transfusion requirements, and organ involvement 2
• Patients with evidence of cardiac iron loading particularly benefit from combination therapy 4, 1
• Combination therapy may be more expensive but offers superior efficacy in severe iron overload cases 4, 1
• Treatment should continue until ferritin levels decline to <1000 ng/mL 2