Deferasirox (Exjade®) for the Treatment of Iron Overload

Cappellini, Maria Domenica; Taher, Ali T.

doi:10.1159/000243801

Cited by 53 publications

(46 citation statements)

References 93 publications

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“…Commercially known as Exjade©, DFX represents a new approach to the management of chronic iron overload in patients with chronic anemias who require blood transfusions [6], [9] and [10]. Currently approved in many countries for the treatment of patients over 2 years of age, its once daily administration leads to high patient satisfaction and compliance [11]. DFX dose between 20 and 30 mg/kg/day generally produces a net negative iron balance [6], however, a recent retrospective study demonstrated that doses of DFX greater than 30 mg/kg/day are safe and more effective in reducing the iron burden [12].…”

Section: Introductionmentioning

confidence: 99%

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

Francia

Massano

Piccione

et al. 2012

Journal of Chromatography B

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We describe a new high performance liquid chromatography coupled with ultraviolet detection method for the quantification of plasma concentration of oral iron chelating agent deferasirox. A simple protein precipitation extraction procedure was applied on 500 μl of plasma aliquots. Chromatographic separation was achieved on a C18 reverse phase column and eluate was monitored at 295 nm, with 8 min of analytical run. This method has been validated following Food and Drug Administration procedures: mean intra and inter day variability was 4.64 and 10.55%; mean accuracy was 6.27%; mean extraction recovery 91.66%. Calibration curves ranged from 0.078125 to 40 μg/ml. Limit of quantification was set at 0.15625 while limit of detection at 0.078125 μg/ml. We applied methodology developed on plasma samples of thalassaemic patients treated with deferasirox, finding correlation between deferasirox plasma concentrations and serum ferritin levels. This methodology allowed a specific, sensitive and reliable determination of deferasirox, that could be useful to perform its therapeutic monitoring and pharmacokinetic studies in patients plasma.

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Section: Introductionmentioning

confidence: 99%

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

Francia

Massano

Piccione

et al. 2012

Journal of Chromatography B

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“…Since 2006, more than 100 publications each on the use of deferasirox and deferiprone in thalassemia have been listed on PubMed, but only a small fraction of these are primary reports of clinical trials, key secondary analyses from trials, or informative studies of pharmacokinetics and ancillary biology. Recent reviews have provided additional information about deferiprone, 45 deferasirox, 6 and optimizing chelation strategies. 7,8 From the large pool of references, selected key studies of both drugs are summarized in Table 2 and in the text below.…”

Section: Introductionmentioning

confidence: 99%

Update on Iron Chelators in Thalassemia

Neufeld

2010

Hematology

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Over the past four decades, there have been dramatic improvements in survival for patients with thalassemia major due in large measure to improved iron chelators. Two chelators are approved for use in the United States and Canada, parenteral deferoxamine and oral deferasirox. Three are available in much of the rest of the world, where oral deferiprone is also approved (in the United States, deferiprone is only available in studies, for emergency use, or on a "compassionate-use" basis). Many trials and worldwide clinical experience demonstrate that each of the three drugs can chelate and remove iron, and thereby prevent or improve transfusional hemosiderosis in thalassemia patients. However, the chelators differ strikingly in side-effect profile, cost, tolerability and ease of adherence, and (to some degree) efficacy for any specific patient. The entire field of chelator clinical trials suffers from the fact that each drug (as monotherapy or in combination) has not been tested directly against all of the other possibilities. Acknowledging the challenges of assessing chelators with diverse properties and imperfect comparative data, the purpose of this review is to summarize the last 4 years of studies that have improved our understanding of the applications and limitations of iron chelators in various settings for thalassemia patients, and to point out areas for much-needed future research.

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“…There is evidence that deferasirox decreases the risk of iron overload in Low and Int-1 IPSS patients [24], removes cardiac iron more effectively, and prevents cardiac iron accumulation [45], and lowers liver iron concentrations and labile plasma iron levels [33] Clinician education about the importance of patient adherence should include this information, as well as such essentials as the potential negative effect of iron overload on heart, liver, and endocrine glands, and the associated increase in mortality risk.…”

Section: Discussionmentioning

confidence: 99%

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

et al. 2011

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 ABSTRACT Transfusion-dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions.Transfusion-dependency is associated with leukemic progression and shorter survival.Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76 and median age at diagnosis of MDS was 74. Patients had received an average of 13.4+7.6 RBC units in the past four months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1550g/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of IPSS, FAB, and/or WHO status, though chelated patients had received more RBC transfusions (p=0.014).Iron chelation therapy may be underutilized in transfusion-dependent patients.

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Deferasirox (Exjade®) for the Treatment of Iron Overload

Cited by 53 publications

References 93 publications

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

Update on Iron Chelators in Thalassemia

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

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