title: Combined therapy with deferoxamine and deferiprone.
abstract: Therapy with either deferiprone (DFP) or deferoxamine (DFO) is inadequate in achieving negative iron balance in many patients with thalassemia. There are mounting theoretical, experimental, and clinical evidences of increased efficacy when therapy includes both chelating agents. DFP and DFO chelate excess iron in different ways without affecting each other's metabolism. When both chelators are administered simultaneously, they interact either in an additive or synergistic manner, probably through "shuttling" iron from DFP to DFO. Iron-balance studies have shown that the use of both agents on the same day can induce negative iron balance in all patients. Long-term combined therapy with DFO with DFP results in considerable reduction of both ferritin levels and liver iron concentration as well as significant improvement in cardiac siderosis and function. This therapeutic regimen is well tolerated and safe, even though it may be related to a small increase in the incidence of agranulocytosis compared with DFP monotherapy. Apart from using both agents simultaneously, sequential administration of DFP and DFO has also shown promising results. Combining the available iron chelators offers many therapeutic options that can be tailored to each patient individually. It is an exciting advance in treating hemosiderosis in thalassemic patients.
authors.affiliation: First Department of Pediatrics, University of Athens, Medical School, Aghia Sophia Children's Hospital, Thivon and Levadias, Goudi 115 27, Greece. ankatt@med.uoa.gr
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
mesh_terms: D000380:Agranulocytosis / Q000139:chemically induced; D001692:Biological Transport; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control; D015913:Chelation Therapy / Q000009:adverse effects; D002986:Clinical Trials as Topic; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D008099:Liver / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine