Effects of deferasirox dose and decreasing serum ferritin concentrations on kidney function in paediatric patients: an analysis of clinical laboratory data from pooled clinical studies

Bird, Steven T.; Swain, Richard S.; Tian, Fang; Okusanya, Ólanrewaju O.; Waldron, Peter; Khurana, Mona; Durmowicz, Elizabeth L; Ma, Yong; Major, Jacqueline M.; Gelperin, Kate

doi:10.1016/s2352-4642(18)30335-3

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…Pediatric patients need to be focused on. The last study reported that DFX causes acute kidney injury (AKI) in a dose-dependent manner, and pediatric patients face a high risk of AKI and a cycle of repeated kidney injury due to a higher DFX exposure at a given eGRF 20. The US Food and Drug Administration recommended dose reduction or interruption when physicians often observed fever or dehydration adverse effects in children receiving DFX 19…”

Section: Introductionmentioning

confidence: 99%

ECONOMIC EVALUATION OF CHELATION REGIMENS FOR Β--Thalassemia MAJOR: A SYSTEMATIC REVIEW

Lin

et al. 2019

Mediterr J Hematol Infect Dis

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Background:Deferoxamine (DFO) or Deferiprone (DFP) or Deferasirox (DFX) monotherapy and DFO and DFP combination therapy were four commonly implemented now chelation regimens for the iron overloaded of β-thalassemia major. This systematic review aims to determine the cost-effectiveness of four chelation regimens and provide evidence for the rational use of chelation regimens for β-thalassemia major therapy in clinic.Methods:A systematic literature search in PubMed, EMBASE (Ovid), CENTRAL (Cochrane library), HTAD (Cochrane library), NHS EED (Cochrane library), CBM, CNKI, VIP, and Wanfang was conducted in April 2018. In addition, a manual search was performed. Two researchers, working independently, selected the papers, extracted the data and assessed the methodological quality of the included papers. Each included paper was evaluated using a checklist developed by Drummond et al. Results:The initial number of records was 968, and eight papers met the final eligibility criteria. All the included eight papers were cost-utility analyses. And the methodological quality of these papers was good. Nineteen studies were included in eight papers. Nine studies of DFX versus DFO had contradictory results. Out of the nineteen studies, three studies of DFX versus DFP established that using DFP was cost-effective. Three studies of DFP versus DFO established that using DFP was cost-effective. One study of DFP and DFO combination therapy versus DFO found that using DFO was cost-effective. One study of DFP and DFO combination therapy versus DFP found that using DFP was cost-effective. And there were two studies of DFP and DFO combination therapy versus DFX, but we cannot be sure which one of two chelation regimens was cost-effective. Conclusion:In brief, DFP is the best choice, followed by DFO or DFX, when an iron chelator is to be used alone for β-thalassemia major therapy. All studies that compared DFO and DFP combination therapy with DFO (or DFP or DFX) monotherapy established that the combination therapy with DFO and DFP was not cost-effective. However, due to the low number of related studies, more extensive, high-quality research is required for further analysis and confirmation of our findings. Moreover, the cost effectiveness is not an absolute issue when in different countries(regions) the results are opposite for other countries(regions). The specific region had a substantial influence on the economy of drugs. Key words: β-thalassemia major, Deferoxamine, Deferiprone, Deferasirox, cost-effectiveness, systematic review

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Section: Introductionmentioning

confidence: 99%

ECONOMIC EVALUATION OF CHELATION REGIMENS FOR Β--Thalassemia MAJOR: A SYSTEMATIC REVIEW

Lin

et al. 2019

Mediterr J Hematol Infect Dis

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“…eGFR was calculated using Cockcroft-Gault and Bedside Schwartz formula for patients aged ≥ 14 and < 14 years, respectively. Acute Kidney Injury (AKI) was defined according to guidelines as previously described 20 , specifically, an episode of AKI was reported if reaching any of the following thresholds: eGFR < 90 mL/min/1.73 m 2 if baseline ≥ 100 mL/min/1.73 m 2 or eGFR < 75% of baseline if otherwise and any case of eGFR < 60 mL/min/1.73 m 2 ). Chronic Kidney Disease (CKD) risk was defined according to guidelines 28 .…”

Section: Design and Methodsmentioning

confidence: 99%

“…A comprehensive analysis requested by the FDA Paediatric Advisory Committee established a clear relationship between high-dose DFX [> 30 mg/kg/day (DT) or > 21 mg/kg/day (FCT or sprinkle granules)], low ferritin (< 1000 μg/L) and the risk of AKI. Analyses of pooled data from three clinical studies found that small decreases in estimated glomerular filtration rate (eGFR) among paediatric patients due to small body surface area are associated with significantly increased DFX plasma concentrations, possibly leading to severe nephrotoxicity in case of over-chelation 20 .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

Piolatto

Berchialla

Allegra

et al. 2021

Sci Rep

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Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose–response correlation [Spearman r (dose-serum ferritin variation): − 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.

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“…This is consistent with the results of hospitalized patients, and plasma ferrous iron levels are positively correlated with AKI risk [ 69 ]. Although both the endogenous and exogenous iron chelation processes have been shown to alleviate tissue injury, using iron chelators in large quantities produces the opposite effect, and due to excessive chelation, the iron content that should maintain the physiological activities of cells is reduced, which can cause multiple organ failure [ 70 – 72 ]. In this section, we emphasize the significance of iron chelation in alleviating tissue damage, but we also stress the adverse effects of excessive chelation on tissues.…”

Section: Ferroptosis and Akimentioning

confidence: 99%

The Cross‐Link between Ferroptosis and Kidney Diseases

Wang

Liu

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Acute and chronic kidney injuries result from structural dysfunction and metabolic disorders of the kidney in various etiologies, which significantly affect human survival and social wealth. Nephropathies are often accompanied by various forms of cell death and complex microenvironments. In recent decades, the study of kidney diseases and the traditional forms of cell death have improved. Nontraditional forms of cell death, represented by ferroptosis and necroptosis, have been discovered in the field of kidney diseases, which have reshuffled the role of traditional cell death in nephropathies. Although interactions between ferroptosis and acute kidney injury (AKI) have been continuously explored, studies on ferroptosis and chronic kidney disease (CKD) remain limited. Here, we have reviewed the therapeutic significance of ferroptosis in AKI and anticipated the curative potential of ferroptosis for CKD in the hope of providing insights into ferroptosis and CKD.

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Effects of deferasirox dose and decreasing serum ferritin concentrations on kidney function in paediatric patients: an analysis of clinical laboratory data from pooled clinical studies

Cited by 15 publications

References 24 publications

ECONOMIC EVALUATION OF CHELATION REGIMENS FOR Β--Thalassemia MAJOR: A SYSTEMATIC REVIEW

ECONOMIC EVALUATION OF CHELATION REGIMENS FOR Β--Thalassemia MAJOR: A SYSTEMATIC REVIEW

Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

The Cross‐Link between Ferroptosis and Kidney Diseases

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