Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

Al-Khabori, Murtadha; Bhandari, Sunil; Al-Huneini, Mohammed; Al-Farsi, Khalil; Panjwani, Vinodh; Daar, Shahina

doi:10.5001/omj.2013.31

Cited by 43 publications

(38 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37,38,40,[60][61][62][63][64][65][66][67][68][69][70][71][72] Among 72 patients with β-thalassaemia major or intermedia who were treated with 20 mg/kg per day of deferasirox for 17 months, an increase in sCr levels >33% above baseline was observed in 46 (64%) patients and deferasirox was discontinued in seven (11%) patients. 60 Serum cystatin C levels are a more sensitive indicator of changes in GFR than are sCr levels. Measurement of serum cystatin C levels disclosed 100% (P <0.001) of nephrotoxicity incidence in a clinical trial in 31 patients with double heterozygous sickle-cell β-thalassaemia, 58 whereas in a clinical practice study of 42 patients with β-thalassaemia, cystatin C levels increased in 36% of patients (n = 15; P = 0.001).…”

Section: Epidemiologymentioning

confidence: 99%

Deferasirox nephrotoxicity—the knowns and unknowns

et al. 2014

View full text Add to dashboard Cite

In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30-100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.

show abstract

Section: Epidemiologymentioning

confidence: 99%

Deferasirox nephrotoxicity—the knowns and unknowns

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Up to 60% of patients with transfusion‐dependent thalassaemia (TDT) have been reported to develop signs of tubular dysfunction 37 . The prevalence of these conditions is bound to increase with advancing age as their presentation is related to both the course of the disease and the use of iron chelators 38,39 . Kidney disease may develop through progressive renal tubular and glomerular damage and renal disease is considered to be the fourth cause of morbidity among patients with TDT, accounting for 4% of deaths, after endocrine (44.7%), cardiovascular (41.3%) and hepatic (40.5%) disease 40 …”

Section: The Evolving Spectrum Of Comorbiditiesmentioning

confidence: 99%

The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation

Farmakis

Giakoumis

Angastiniotis³

et al. 2020

European J of Haematology

View full text Add to dashboard Cite

Therapeutic advances in β‐thalassaemia have gradually lead to a significant improvement in prognosis over the past few decades. As a result, patients living in areas where disease‐specific programmes offering access to modern therapy are in place experience a new era of prolonged survival that tends to reach that of the normal population. This ageing thalassaemia population, however, faces a new spectrum of comorbidities resulting from increasing age that may jeopardise the advances in prognosis provided by current therapy and thus poses new challenges in diagnosis, monitoring and treatment. In this position paper of the Thalassaemia International Federation, we review the changing epidemiology and clinical spectrum of patients with β‐thalassaemia and propose actions to be undertaken in order to address the emerging spectrum of comorbidities resulting from ageing.

show abstract

“…EDTA, deferiprone, deferasirox, deferromine, etc. but due to lack of specificity to bind only to iron along with its side effects like nephrotoxicity, dehydration, low blood calcium, allergy, it is important to search out some really effective drugs for iron chelation that possess least side effects [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective Role of <i>Phlogacanthus thyrsiflorus </i>Nees as a Potential Iron Chelating Drug

Saikia¹,

Das²,

Saikia

2019

IJPPE

View full text Add to dashboard Cite

Exceeding iron levels in the body get accumulated in the liver and other vital organs that induce oxidative stress in the affected areas, which is clinically diagnosed as "iron overload". Present study was undertaken to investigate the role of Phlogacanthus thyrsiflorus Nees, an endemic species of North-east India, in ameliorating such diseased conditions. Our results indicate that the methanolic leaf extract of Phlogacanthus thyrsiflorus (PTME) exhibits excellent iron chelation and antioxidant activities in dose dependent manner in vitro. To understand the in vivo conditions, thirty six mice were divided into six groups which were treated with differing doses of PTME. Levels of serum markers ALT and AST significantly elevates during diseased conditions but PTME treated mice have shown a marked decrease in the group (S200) by 39.24 and 17.24%. On the contrary lowering levels of liver antioxidant enzymes (GST, GSH, SOD and CAT) indicates stress. But 200mg/kg b.w. of PTME treated groups restored the enzyme to optimum levels. Morphological changes were observed through histopathological analysis of liver tissues and we found significant differences in them. PTME was found to be completely nontoxic in the in vivo treatment, suggesting its feasibility as a safe oral drug. The above study suggests that PTME contributed to its free radical scavenging and iron chelation activity; however, further studies are required for the assessment of the phytoconstituents and the pathways through which it act to treat iron-overload diseases.SciPress applies the CC-BY 4.0 license to works we publish: https://creativecommons.org/licenses/by/4.0/ 2.7. In vitro study Iron Chelation AssayThe ferrous ion chelating activity was evaluated by a standard method [15] with minor changes. The reaction was carried out in 20 mM HEPES buffer of pH 7.2. To 12.5 μM ferrous sulphate solution different concentrations (0-120 μg/ml) of plant extract were added. The reaction International Journal of Pharmacology, Phytochemistry and EthnomedicineVol. 12 13[18] P. Kakkar, B. Das, P.N. Viswanathan, A modified spectrophotometric assay of superoxide dismutase, Indian J.

show abstract

Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

Abstract: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

Cited by 43 publications

References 8 publications

Deferasirox nephrotoxicity—the knowns and unknowns

Deferasirox nephrotoxicity—the knowns and unknowns

The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation

Hepatoprotective Role of <i>Phlogacanthus thyrsiflorus </i>Nees as a Potential Iron Chelating Drug

Contact Info

Product

Resources

About