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Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine.
MedLine Citation:
PMID:  22875626     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background. β-Thalassemia patients 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 had 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. Design and Methods. We conducted 34-day metabolic iron balance studies in six patients wherein 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 being 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, hematological parameters, serum chemistries, ferritin levels and urinalyses were determined. Results. All patients were in negative iron balance when treated with deferoxamine alone while 4/6 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. 5/6 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 or urinalyses performed. Conclusions. 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 presenting a convenient way to tailor chelation therapy to the individual needs of each patient. clinicaltrials.gov identifier: NCT00738413.
Authors:
Robert W Grady; Renzo Galanello; Rachel E Randolph; Dorothy Kleinert; Carlo Dessi; Patricia J Giardina
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  Haematologica     Volume:  -     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
USA;
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