Iron Chelation Therapy in Haemochromatosis

Introduction to Chelation Therapy

The European Medicines Agency recommends iron chelation therapy when phlebotomy is not possible, with deferasirox as the primary second-line option at a starting dose of 10 mg/kg/day, requiring careful risk-benefit consideration and contraindicated in patients with advanced liver disease 1, 2

Deferasirox represents the most studied chelation option in haemochromatosis, effective at reducing iron burden, but with weak evidence and not approved by the European Medicines Agency for this indication 1, 2
The target serum ferritin during iron depletion is 50 μg/L, maintaining 50-100 μg/L thereafter, as recommended by the European Medicines Agency 1, 2
Deferasirox dosing starts at 10 mg/kg/day, based on phase I/II trials showing a 75% reduction in median serum ferritin over 48 weeks to <250 ng/mL, as per the European Medicines Agency guidelines 3

Chelation therapy should be considered in situations where phlebotomy cannot be performed, including inaccessible veins, severe needle phobia, concomitant anemia, life-threatening cardiac iron overload, and conditions where bloodletting would cause harm, as recommended by the European Medicines Agency 3, 5
The American College of Cardiology recommends combined chelation therapy with deferiprone and deferoxamine for life-threatening cardiac iron overload in juvenile haemochromatosis, though phlebotomy remains first-line when possible 4, 3

All iron chelation drugs are contraindicated in pregnancy, as stated by the European Medicines Agency 4
Patients requiring chelation therapy should be referred to specialized centers with expertise in iron disorders for evaluation and treatment, as recommended by the European Medicines Agency 4, 3

The European Medicines Agency explicitly contraindicates the use of deferasirox in cirrhotic patients, as it can cause hepatic failure 1, 4
The European Medicines Agency recommends avoiding overchelation, targeting a ferritin level of 50 μg/L to prevent iron deficiency 1, 2
The European Medicines Agency recognizes that chelation is off-label, as deferasirox is not approved for haemochromatosis 1, 2