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British Journal of Haematology Oct 2019
Topics: Bone Marrow Cells; DNA Damage; Deferasirox; Hematopoiesis; Humans; Iron; Iron Chelating Agents; Iron Overload; Oxidative Stress
PubMed: 31172507
DOI: 10.1111/bjh.16012 -
Cureus Nov 2023Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an... (Review)
Review
Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an optimal chelating regimen. Deferasirox (DFX) and deferiprone (DFP) are two oral iron chelators, and combination usage demonstrated effectiveness as an alternative to monotherapies in patients with a limited response to monotherapy. The present systematic review aimed to assess the evidence regarding the outcomes of combined DFP and DFX in iron-overloaded patients. An online search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. Interventional and observational studies that assessed the outcomes of combined DFP and DFX in iron-overloaded patients were included. Eleven studies (12 reports) were considered in this meta-analysis. The studies included dual iron chelation strategies for a number of diagnoses. Single-arm studies (n =7) showed a reduction of serum ferritin, which reached the level of statistical significance in three studies. Likewise, most studies reported a numerical reduction in liver iron concentration (LIC) and increased cardiac MRI-T2* values after chelating therapy. Alternatively, comparative studies showed no significant difference in post-treatment serum ferritin between DFX plus DFP and DFX/DFP plus deferoxamine (DFO). The adherence to combination therapy was good to average in nearly 66.7-100% of the patients across four studies. One study reported a poor adherence rate. The combined regimen was generally tolerable, with no reported incidence of serious adverse events among the included studies. In conclusion, the DFP and DFX combination is a safe and feasible option for iron overload patients with a limited response to monotherapy.
PubMed: 38058350
DOI: 10.7759/cureus.48276 -
Vox Sanguinis Aug 2021Deferasirox is an oral chelator approved for iron overload, which has a potential side effect of renal Fanconi syndrome, with proximal tubular dysfunction and tubular... (Review)
Review
BACKGROUND AND OBJECTIVES
Deferasirox is an oral chelator approved for iron overload, which has a potential side effect of renal Fanconi syndrome, with proximal tubular dysfunction and tubular acidosis. Monitoring of renal function is recommended, though no standard for monitoring exists. We aim to describe cases of deferasirox-associated Fanconi syndrome in adults and the renal monitoring required to detect these findings.
MATERIALS AND METHODS
We present a review of the literature and six cases from our institution of deferasirox-associated partial Fanconi syndrome in adult patients with transfusional iron overload secondary to β-thalassemia or Diamond Blackfan Anaemia.
RESULTS
While prior cases in the literature occurred at high doses of deferasirox, our series included patients on doses as low as deferasirox 10 mg/kg who had been aggressively chelated. All patients had resolution of laboratory abnormalities with drug interruption.
CONCLUSION
Rather than chelating to normal iron levels, this series supports prior suggestions that deferasirox dose be reduced if ferritin <500-1000 ng/ml, and also supports dose reduction if liver iron content <3 mg iron per g dry weight or for those undergoing aggressive chelation with rapid decrease in iron. Monitoring with metabolic panel and urinalysis were sufficient to detect clinically significant proximal tubular dysfunction, but should be followed up with additional studies to confirm the diagnosis while deferasirox dose is decreased or held.
Topics: Adult; Benzoates; Deferasirox; Fanconi Syndrome; Humans; Iron Chelating Agents; Iron Overload; Triazoles
PubMed: 33529394
DOI: 10.1111/vox.13064 -
Frontiers in Bioengineering and... 2022Iron as an essential element, is involved in various cellular functions and maintaining cell viability, cancer cell is more dependent on iron than normal cell due to its...
Iron as an essential element, is involved in various cellular functions and maintaining cell viability, cancer cell is more dependent on iron than normal cell due to its chief characteristic of hyper-proliferation. Despite that some of the iron chelators exhibited potent and broad antitumor activity, severe systemic toxicities have limited their clinical application. Polyaminoacids, as both drug-delivery platform and therapeutic agents, have attracted great interests owing to their different medical applications and biocompatibility. Herein, we have developed a novel iron nanochelator PL-DFX, which composed of deferasirox and hyperbranched polylysine. PL-DFX has higher cytotoxicity than DFX and this effect can be partially reversed by Fe supplementation. PL-DFX also inhibited migration and invasion of cancer cells, interfere with iron metabolism, induce phase G1/S arrest and depolarize mitochondria membrane potential. Additionally, the anti-tumor potency of PL-DFX was also supported by organoids derived from clinical specimens. In this study, DFX-based iron nanochelator has provided a promising and prospective strategy for cancer therapy iron metabolism disruption.
PubMed: 36518196
DOI: 10.3389/fbioe.2022.1078137 -
Life Sciences Apr 2021Deferasirox (DFX) was formulated into oil-in-water microemulsions in the presence of pluronicto improve its oral bioavailability. The size of the...
Deferasirox (DFX) was formulated into oil-in-water microemulsions in the presence of pluronicto improve its oral bioavailability. The size of the DFX-loadedmicroemulsions system measured by dynamic light scattering (DLS) was about 9 nm. The anti-proliferative and anti-lipid peroxidation effects of DFX and DFX-loaded microemulsions were assessed on Human umbilical vein endothelial (HUVEC) cells. Our in vitro results showed that HUVEC cells are more susceptible to free DFX as compared to DFX-loaded microemulsions. Although both free and encapsulated DFX attenuated FeCl-induced lipid peroxidation, after 6 and 12 h treatment, DFX-loaded microemulsions did not appear a better ameliorator than DFX. To compare the in vivo efficacy of free DFX and DFX-loaded microemulsions in iron- intoxicated rats, the animals were orally administered with 25 mg/kg DFX, or 25 mg/kg DFX microemulsions, respectively. In vivo gavage handling of free DFX significantly increased serum biochemical parameters. There was also a significant increase in lipid peroxidation in rats who received free DFX compared to those in the control rats. Treatment with DFX-loaded microemulsions restored the elevated levels of serum AST, ALT, and creatinine levels and also reduced liver MDA content. Histopathological analysis of renal and hepatic tissues was in line with the biochemical results. In conclusion, DFX-loaded microemulsions induce less toxicity than free DFX and appear a more desirable and safer drug carrier in combating the iron-overload complications. Theoretical simulations are performed to get better insight regarding interactions between DFX and surfactant F127.
Topics: Animals; Deferasirox; Drug Delivery Systems; Emulsions; Human Umbilical Vein Endothelial Cells; Humans; Iron; Iron Chelating Agents; Iron Overload; Lipid Peroxidation; Liver; Male; Micelles; Rats; Rats, Wistar
PubMed: 33545199
DOI: 10.1016/j.lfs.2021.119146 -
Journal of Trace Elements in Medicine... 2015The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The... (Review)
Review
The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.
Topics: Administration, Oral; Antidotes; Benzoates; Chelating Agents; Deferasirox; Deferiprone; Deferoxamine; Heavy Metal Poisoning; Humans; Penicillamine; Poisoning; Pyridones; Succimer; Triazoles; Trientine; Unithiol
PubMed: 25457281
DOI: 10.1016/j.jtemb.2014.10.001 -
BMJ Open Feb 2024Despite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per...
Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial.
INTRODUCTION
Despite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.
METHODS AND ANALYSIS
This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures.
ETHICS AND DISSEMINATION
Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals.
TRIAL REGISTRATION NUMBER
The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).
Topics: Adult; Adolescent; Humans; Deferasirox; Deferiprone; Deferoxamine; beta-Thalassemia; Benzoates; Triazoles; Pyridones; Iron Overload; Iron Chelating Agents; Iron; Randomized Controlled Trials as Topic
PubMed: 38331857
DOI: 10.1136/bmjopen-2023-077342 -
The Lancet. Child & Adolescent Health Jan 2019
Topics: Child; Deferasirox; Ferritins; Humans
PubMed: 30455111
DOI: 10.1016/S2352-4642(18)30350-X -
Critical Reviews in Analytical Chemistry 2020Acute iron poisoning and chronic iron overload consequences in significant morbidity and mortality worldwide. Treatment of acute iron poisoning and chronic iron overload... (Review)
Review
Acute iron poisoning and chronic iron overload consequences in significant morbidity and mortality worldwide. Treatment of acute iron poisoning and chronic iron overload can be challenging and care providers are often tackled with management dilemmas. Iron chelating agents are commonly prescribed for patients with iron deficiency anemia. In this review article, different analytical techniques are reported used for qualitative and quantitative analysis of iron chelating agents like, deferiprone, deferoxamine, and deferasirox. Efforts are taken to collect all related articles published till October 2018. This review discusses all analytical methods, its advantages and disadvantages as well as its applications. This article will help you to know about basic analytical techniques as well as advanced hyphenated techniques practiced for determination of iron chelating agents in different matrices. The techniques discussed in this review follow the ICH guidelines for method validation.
Topics: Humans; Iron Chelating Agents
PubMed: 31140834
DOI: 10.1080/10408347.2019.1620095 -
Profiles of Drug Substances,... 2024Deferasirox is an iron-chelating drug developed by Novartis company for treatment of diseases accompanied by chronic iron overload; such as β-thalassemia or sickle cell...
Deferasirox is an iron-chelating drug developed by Novartis company for treatment of diseases accompanied by chronic iron overload; such as β-thalassemia or sickle cell diseases. Owing to its advantages such as high affinity, specificity and wide therapeutic window, it is considered as first line treatment. The current chapter describes the physicochemical characteristics, mode of action, pharmacokinetics, therapeutic applications and synthetic methods for deferasirox. Moreover, it includes Fourier transform infrared spectrometry (FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis for its functional groups. In addition, the selected analytical methods are summarized to aid the analysts in their routine analysis of deferasirox.
Topics: Humans; Deferasirox; Benzoates; Triazoles; Iron Chelating Agents; Iron Overload; Iron
PubMed: 38423705
DOI: 10.1016/bs.podrm.2023.11.001