Desferrioxamine (DFX) remains the most effective and safe
iron chelator for treatment of patients with transfusional
iron overload. It is usually given by intermittent
subcutaneous infusions for 8-12 h on 4-6 days weekly using a battery-driven pump. Disposable balloon infusers provide a suitable method of giving continuous
subcutaneous infusions with improved patient compliance. For patients with cardiac abnormalities due to
iron overload, continuous intravenous
desferrioxamine is essential to eliminate toxic plasma non-
transferrin bound
iron and to reduce body
iron stores.
Deferiprone (L1, l-2 dimethyl-3hydroxy-pyrid-4-one) is a less effective
iron chelator but has the advantage of being orally active. Long-term trials in which patients have taken 75 mg/kg/day have shown that
deferiprone is capable of maintaining body
iron stores at safe levels in a proportion of thalassaemia major patients but body
iron stores, assessed by liver biopsy remain at high levels (> 15.0 mg/g dry weight) in a substantial number of patients. These concentrations have been associated with tissue damage. Trials of increased doses of
deferiprone (up to 100 mg/kg/day) or of combined
therapy with daily
deferiprone and DFX or 1 or 2 days each week are being carried out in an attempt to achieve lower body
iron burden in these patients. Preliminary results show that the drugs can be given safely together and urine
iron excretion produced is additive, implying that the drugs chelate different body
iron pools. Patients previously well chelated with serum
ferritin levels less than 2500 micrograms/L have the fewest side-effects from
deferiprone and usually may be kept at the same level of body
iron for periods of at least 4 years, assessed by serum
ferritin and urine
iron excretion. The side-effects of
deferiprone result in some patients discontinuing
therapy. These side-effects, especially
arthropathy, mainly occur in previously poorly chelated and so the most heavily
iron-loaded patients.
Nausea and other gastrointestinal symptoms,
agranulocytosis or milder degrees of
neutropenia account with
arthropathy for nearly all the withdrawals from
deferiprone therapy. Patients with
cardiomyopathy due to
iron overload should be given intravenous DFX rather than
deferiprone.
Deferiprone, licensed for
pharmaceutical use in India, awaits official approval for widespread clinical use in Western Europe and North America. Meanwhile, attempts to find new orally active
iron chelators and improved methods of administration of
desferrioxamine are in progress.