title: Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine.
abstract: Patients with β-thalassemia require iron chelation therapy to protect against progressive iron overload and non-transferrin-bound iron. Some patients fail to respond adequately to deferoxamine and deferasirox monotherapy while others have side effects which limit their use of these drugs. Since combining deferiprone and deferoxamine has an additive effect, placing all patients into net negative iron balance, we investigated the possibility that combining deferasirox and deferoxamine would lead to similar results. We conducted 34-day metabolic iron balance studies in six patients in whom the relative effectiveness of deferasirox (30 mg/kg/day) and deferoxamine (40 mg/kg/day) was compared, alone and in combination. Patients consumed fixed low-iron diets; daily urinary and stool iron excretion were determined by atomic absorption. Red blood cell transfusions were given prior to each drug treatment to minimize the effects of ineffective erythropoiesis. Serial safety measures, hematologic parameters, serum chemistries, ferritin levels and urinalyses were determined. All patients were in negative iron balance when treated with deferoxamine alone while four of six patients remained in positive balance when deferasirox monotherapy was evaluated. Daily use of both drugs had a synergistic effect in two patients and an additive effect in three others. Five of six patients would be in negative iron balance if they used the combination of drugs just 3 days a week. No significant or drug-related changes were observed in the blood work-ups or urinalyses performed. We conclude that supplementing the daily use of deferasirox with 2 - 3 days of deferoxamine therapy would place all patients into net negative iron balance thereby providing a convenient way to tailor chelation therapy to the individual needs of each patient.
authors.affiliation: Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital, New York, NY, USA. rwgrady13@gmail.com
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grady
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Randolph
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Kleinert
authors.forename: Carlo
authors.initials: C
authors.lastname: Dessi
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Giardina
mesh_terms: D000328:Adult; D001565:Benzoates / Q000008:administration & dosage*; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood / Q000652:urine; D007502:Iron Chelating Agents / Q000008:administration & dosage; D008297:Male; D014230:Triazoles / Q000008:administration & dosage*; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox