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© 2003 Elsevier, reprinted with permission
Three approved iron chelating agents are available currently - deferasirox, deferoxamine and deferiprone - although the availability of these agents is country specific. Deferoxamine has been available for approximately 40 years and has established beyond doubt the value of chelation therapy in iron overloaded patients. Long-term data have demonstrated that deferoxamine is highly efficacious in reducing stored iron and the complications of iron overload [2;3]. It is indicated in most countries as treatment for chronic iron overload and for acute iron poisoning [4] [Please refer to your local prescribing information]. The demanding administration regimen of lengthy infusions (8-12 hours, 5-7 days per week) has, however, proved to be a distinct limitation [5;6].
The first oral iron chelating agent, deferiprone, was approved in 1999 and is available in Europe and in a number of other countries, but not in the United States and Canada. Deferiprone requires three-times daily administration (at doses of 25 mg/kg) and is indicated in Europe for the treatment of iron overload in patients with thalassaemia major when deferoxamine therapy is contraindicated or inadequate [7] [Please refer to your local prescribing information].
Most recently, the once-daily oral iron chelating agent, deferasirox has become commercially available and is now widely approved. Data support the use of deferasirox in adult and pediatric patients for the treatment of chronic iron overload due to blood transfusions [8] [Please refer to your local prescribing information].Although local prescribing information varies, the recommended starting dose is generally 20 mg/kg/day. A dose of 30 mg/kg/day may be considered for patients receiving >14 mL/kg/month of packed red blood cells (approximately >4 units/month) when the therapeutic goal is iron reduction, while a dose of 10 mg/kg/day may be considered for patients receiving <7 mL/kg/month (approximately <2 units/month) in whom the therapeutic goal is maintenance of body iron levels [8]. Deferasirox has dose-dependent efficacy that is comparable to deferoxamine at similar doses, and has a defined safety profile, which is clinically manageable with appropriate patient monitoring [9-11].
In this section:
Deferoxamine iron chelating agent
First introduced in the early 1960s, deferoxamine is still the reference standard iron chelating agent. Deferoxamine (known as 'desferrioxamine' in some countries) has been proven to markedly improve survival in transfusion-related iron overload [12-14].
Deferoxamine is poorly absorbed orally and is rapidly metabolized, and must therefore be administered in prolonged subcutaneous or intravenous infusions that sustain plasma levels at the therapeutic plateau. As patients with severe chronic anemia face a lifetime of regular blood transfusions and daily or almost-daily iron chelation infusions, compliance with this demanding regimen can be a significant problem [5;6].
The development of a small, ambulatory pump capable of delivering a continuous mini-infusion over 8-24 hours has helped many patients comply with therapy. However, the pump does not solve the problems of infusion-site reactions and pain.
Deferoxamine has a very high and selective affinity for iron. Each molecule binds tightly to one atom of labile iron. This, in combination with the molecule's ability to pass through cell walls, enables deferoxamine to remove both extracellular and intracellular labile iron [15].
Deferoxamine chelates labile iron both in reticuloendothelial macrophages, where it becomes available for urinary excretion by the kidneys, and in hepatocytes, where it is excreted into the gut via bile.
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