858
Views
23
CrossRef citations to date
0
Altmetric
Drug Evaluations

Deferasirox: pharmacokinetics and clinical experience

, &
Pages 123-134 | Published online: 19 Dec 2011

Bibliography

  • Kohgo Y, Ikuta K, Ohtake T, Body iron metabolism and pathophysiology of iron overload. Int J Hematol 2008;8:7-15
  • Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann NY Acad Sci 1998;850:191-201
  • Pippard MJ, Callender ST, Warner GT, Weatherall DJ. Iron absorption and loading in beta-thalassaemia intermedia. Lancet 1979;2:819-21
  • Pootrakul P, Huebers HA, Finch CA, Iron metabolism in thalassemia. Birth Defects Orig Artic Ser 1988;23:3-8
  • Borgna-Pignatti C, Rugolotto S, De Stefano P, Survival and disease complications in thalassemia major. Ann NY Acad Sci 1998;850:227-31
  • Kattamis C, Liakopoulou T, Kattamis A. Growth and development in children with thalassaemia major. Acta Paediatr Scand Suppl 1990;366:111-17
  • Ladis V, Chouliaras G, Berdousi H, Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann NY Acad Sci 2005;1054:445-50
  • Low LC. Growth of children with beta-thalassemia major. Indian J Pediatr 2005;72:159-64
  • Modell B, Khan M, Darlison M. Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet 2000;355:2051-2
  • Desferal® (deferoxamine) Basic Prescribing Information. 2010. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/desferal.pdf
  • Cappellini MD, Pattoneri P. Oral iron chelators. Annu Rev Med 2009;60:25-38
  • Cohen AR. New advances in iron chelation therapy. Hematology Am Soc Hematol Educ Program 2006;2006(1):42-7
  • Neufeld EJ. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 2006;107:3436-41
  • Ferriprox prescribing information. 2007. Available from: http://www.ferriprox.com
  • Westwood M, Anderson LJ, Pennell DJ. Treatment of cardiac iron overload in thalassemia major. Haematologica 2003;88:481-2
  • Borgna-Pignatti C, Cappellini MD, De Stefano P, Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood 2006;107:3733-7
  • Pennell DJ, Berdoukas V, Karagiorga M, Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006;107:3738-44
  • Piga A, Gaglioti C, Fogliacco E, Tricta F. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica 2003;88:489-96
  • Origa R, Bina P, Agus A, Combined therapy with deferiprone and desferrioxamine in thalassemia major. Haematologica 2005;90:1309-14
  • Kattamis A, Ladis V, Berdousi H, Iron chelation treatment with combined therapy with deferiprone and deferoxamine: a 12-month trial. Blood Cells Mol Dis 2006;36:21-5
  • Tanner MA, Galanello R, Dessi C, A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation 2007;115:1876-84
  • Tanner MA, Galanello R, Dessi C, Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson 2008;10:12
  • Farmaki K, Tzoumari I, Pappa C, Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major. Br J Haematol 2010;148:466-75
  • EXJADE® (deferasirox) US Prescribing Information. 2011. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/exjade.pdf.
  • Rienhoff HY Jr, Viprakasit V, Tay L, A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica 2011;96:521-5
  • El Ouagari K, Migliaccio-Walle K, Lau H, Bozkaya D. Cost-effectiveness of deferasirox in lower-risk myelodysplastic syndrome (MDS) in Canada [abstract 343]. Leuk Res 2011;35:S137-8
  • Calabro A, Delea TE, Sofrygin O, Cost-effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassemic patients: a Brazilian perspective. Haematologica 2006;91(Suppl 1):abstract 804
  • Delea TE, Thomas SK, Baladi J, Phatak PD. Cost-effectiveness analysis of oral iron chelation therapy with deferasirox (Exjade®, ICL670) versus infusional chelation therapy with deferoxamine in patients with transfusion-dependent myelodysplastic syndrome. Blood 2005;106(11):abstract 5585
  • Glickstein H, El RB, Shvartsman M, Cabantchik ZI. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 2005;106:3242-50
  • Glickstein H, El BR, Link G, Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood 2006;108:3195-203
  • Daar S, Pathare A, Nick H, Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia. Eur J Haematol 2009;82:454-7
  • Nick H, Wong A, Acklin P, ICL670A: preclinical profile. Adv Exp Med Biol 2002;509:185-203
  • Nick H, Acklin P, Lattmann R, Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr Med Chem 2003;10:1065-76
  • Nick H. Deferasirox (Exjade®, ICL670) preclinical overview. Semin Hematol 2007;44:S12-15
  • Waldmeier F, Bruin GJ, Glaenzel U, Pharmacokinetics, metabolism, and disposition of deferasirox in beta-thalassemic patients with transfusion-dependent iron overload who are at pharmacokinetic steady state. Drug Metab Dispos 2010;38:808-16
  • Piga A, Galanello R, Forni GL, Randomized phase II trial of deferasirox (Exjade®, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica 2006;91:873-80
  • Galanello R, Origa R. Once-daily oral deferasirox for the treatment of transfusional iron overload. Expert Rev Clin Pharmacol 2008;1:231-40
  • Galanello R, Piga A, Alberti D, Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia. J Clin Pharmacol 2003;43:565-72
  • Galanello R, Piga A, Forni GL, Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with beta-thalassemia major. Haematologica 2006;91:1343-51
  • Cappellini MD, Cohen A, Piga A, A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood 2006;107:3455-62
  • Chang HH, Lu MY, Liao YM, Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for patients with transfusion-dependent beta-thalassemia. Pediatr Blood Cancer 2011;56:420-4
  • Chirnomas D, Smith AL, Braunstein J, Deferasirox pharmacokinetics in patients with adequate versus inadequate response. Blood 2009;114:4009-13
  • Chirnomas D, Yakhkind A, Paley CS, Neufeld EJ. Strategies to improve iron chelation in thalassemia patients poorly responsive to deferasirox. Blood 2010;116(21):abstract 4279
  • Skerjanec A, Wang J, Maren K, Rojkjaer L. Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers. J Clin Pharmacol 2010;50:205-13
  • Galanello R, Piga A, Cappellini MD, Effect of food, type of food, and time of food intake on deferasirox bioavailability: recommendations for an optimal deferasirox administration regimen. J Clin Pharmacol 2008;48:428-35
  • Sechaud R, Dutreix C, Balez S, Relative bioavailability of deferasirox tablets administered without dispersion and dispersed in various drinks. Int J Clin Pharmacol Ther 2008;46:102-8
  • Taher A, Cappellini MD, Vichinsky E, Efficacy and safety of deferasirox doses of > 30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload. Br J Haematol 2009;147:752-9
  • Cappellini MD, Porter JB, El-Beshlawy A, Tailoring iron chelation by iron intake and serum ferritin trends: the prospective multicenter EPIC study of deferasirox in 1744 patients with various transfusion-dependent anemias. Haematologica 2010;95:557-66
  • Gattermann N. Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Leuk Res 2007;31(Suppl 3):S10-15
  • Thalassaemia International Federation. Guidelines for the clinical management of thalassaemia, 2nd Revised Edition. 2008. Available from: http://www thalassaemia org cy/pdf/Guidelines_2nd_revised_edition_EN pdf
  • Cappellini MD, Bejaoui M, Agaoglu L, Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood 2011;118:884-93
  • Gattermann N, Finelli C, Della Porta M, Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: results from the large 1-year EPIC study. Leuk Res 2010;34:1143-50
  • Lee J-W, Yoon S-S, Shen ZX, Iron chelation therapy with deferasirox in patients with aplastic anemia: A subgroup analysis of 116 patients from the EPIC trial. Blood 2010;116:2448-54
  • Porter J, Galanello R, Saglio G, Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study. Eur J Haematol 2008;80:168-76
  • Anderson LJ, Holden S, Davis B, Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001;22:2171-9
  • Pennell D, Porter JB, Cappellini MD, Continued improvement and normalization of myocardial T2* in patients with beta-thalassemia major treated with deferasirox (Exjade®) for up to 3 years. Blood 2010;116(21):abstract 4276
  • Pennell DJ, Porter JB, Cappellini MD, Continued improvement in myocardial T2* over 2 years of deferasirox therapy in beta-thalassemia major patients with cardiac iron overload. Haematologica 2011;96:48-54
  • Pennell DJ, Porter JB, Cappellini MD, Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia. Blood 2010;115:2364-71
  • Galanello R, Agus A, Campus S, Combined iron chelation therapy. Ann NY Acad Sci 2010;1202:79-86
  • Lal A, Sweeters N, Ng V, Combined chelation therapy with deferasirox and deferoxamine in transfusion-dependent thalassemia. Blood 2010;116(21):abstract 4269
  • Ghoti H, Fibach E, Merkel D, Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes. Haematologica 2010;95:1433-4
  • Rose C, Brechignac S, Vassilief D, Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM. Leuk Res 2010;34:864-70
  • Fox F, Kundgen A, Nachtkamp K, Matched-pair analysis of 186 MDS patients receiving iron chelation therapy or transfusion therapy only. Blood 2009;114(22):abstract 1747
  • Vichinsky E, Bernaudin F, Forni GL, Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease. Br J Haematol 2011;154:387-97
  • Aydinok Y, Agaoglu L, Bejaoui M, Growth and development of paediatric patients with beta-thalassaemia treated with deferasirox for up to 5 years. Haematologica 2010;95(Suppl 2):abstract 1040
  • Taher A, El-Beshlawy A, Elalfy MS, Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study. Eur J Haematol 2009;82:458-65
  • Taher A, Elalfy MS, Al ZK, Importance of optimal dosing >/= 30 mg/kg/d during deferasirox treatment: 2.7-year follow-up from the ESCALATOR study in patients with beta-thalassaemia. Eur J Haematol 2011;87:355-65
  • Ladis V, Berdousi H, Gotsis E, Kattamis A. Deferasirox administration for the treatment of non-transfusional iron overload in patients with thalassaemia intermedia. Br J Haematol 2010;151:504-8
  • Phatak P, Brissot P, Wurster M, A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology 2010;52:1671-9
  • Voskaridou E, Plata E, Douskou M, Treatment with deferasirox (Exjade) effectively decreases iron burden in patients with thalassaemia intermedia: results of a pilot study. Br J Haematol 2010;148:332-4
  • Deugnier Y, Turlin B, Ropert M, Improvement in liver pathology of patients with beta-thalassemia treated with deferasirox for at least 3 years. Gastroenterology 2011;141(4):1202-11
  • Gattermann N, Finelli C, Porta MD, Hematologic responses in myelodysplastic syndromes (MDS) patients treated with deferasirox: an EPIC post-hoc analysis using International Working Group (IWG) 2006 criteria. Blood 2010;116(21):abstract 2912
  • Piga A, Fracchia S, Lai ME, Effect of deferasirox on renal haemodynamics in patients with beta-thalassaemia: first interim analysis. Haematologica 2010;95(Suppl 2):abstract 1798
  • Schmid M, Cappellini MD, Porter JB, Safety of deferasirox (Exjade®) in myelodysplastic syndromes (MDS) and non-MDS patients with transfusional iron overload: a pooled analysis focusing on renal function. Blood 2009;114(22):abstract 1768
  • Even-Or E, Becker-Cohen R, Miskin H. Deferasirox treatment may be associated with reversible renal Fanconi syndrome. Am J Hematol 2010;85:132-4
  • Grange S, Bertrand DM, Guerrot D, Acute renal failure and Fanconi syndrome due to deferasirox. Nephrol Dial Transplant 2010;25:2376-8
  • Rafat C, Fakhouri F, Ribeil JA, Fanconi syndrome due to deferasirox. Am J Kidney Dis 2009;54:931-4
  • Rheault MN, Bechtel H, Neglia JP, Kashtan CE. Reversible Fanconi syndrome in a pediatric patient on deferasirox. Pediatr Blood Cancer 2011;56:674-6
  • Wei HY, Yang CP, Cheng CH, Lo FS. Fanconi syndrome in a patient with beta-thalassemia major after using deferasirox for 27 months. Transfusion 2011;51:949-54
  • Yacobovich J, Stark P, Barzilai-Birenbaum S, Acquired proximal renal tubular dysfunction in beta-thalassemia patients treated with deferasirox. J Pediatr Hematol Oncol 2010;32:564-7
  • Piga A, Kebaili K, Galanello R, Cumulative efficacy and safety of 5-year deferasirox (Exjade®) treatment in pediatric patients with thalassemia major: a phase II multicenter prospective trial. Blood 2008;112(11):abstract 5413
  • Vichinsky E, Onyekwere O, Porter J, A randomized comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol 2007;136:501-8
  • Porter JB, Lin KH, Beris P, Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias. Eur J Haematol 2011;87:338-48

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.