Advances in iron chelation therapy: transitioning to a new oral formulation

Shah, Nirmish

doi:10.7573/dic.212502

Cited by 30 publications

(41 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Iron overload therapy has mainly been limited to removal of excess iron stores using iron-chelating agents [36]. However, all forms of chelation therapy present certain dose-limiting renal and hepatic toxicity, may suffer from compliance issues, and can be cost prohibitive [36,37]. Our findings lend support to the notion that targeting NOX2 [38] at the cardiac myocyte level could be a novel and beneficial strategy for the treatment of iron-overload induced contractile dysfunction.…”

Section: Discussionmentioning

confidence: 54%

“…These findings support the concept that NADPH oxidase/NOX2 is necessary and sufficient for iron overload-mediated oxidative stress, leading to eventual development of cardiac dysfunction. Iron overload therapy has mainly been limited to removal of excess iron stores using iron-chelating agents [36]. However, all forms of chelation therapy present certain dose-limiting renal and hepatic toxicity, may suffer from compliance issues, and can be cost prohibitive [36,37].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

Mak

Kramer

Chmielinska

et al. 2020

Hearts

View full text Add to dashboard Cite

The role of NADPH oxidase subunit, gp91phox (NOX2) in development of oxidative stress and cardiac dysfunction due to iron (Fe)-overload was assessed. Control (C57BL/6J) and gp91phox knockout (KO) mice were treated for up to 8 weeks with Fe (2.5 mg/g/wk, i.p.) or Na-dextran; echocardiography, plasma 8-isoprostane (lipid peroxidation marker), cardiac Fe accumulation (Perl’s staining), and CD11b+ (WBCs) infiltrates were assessed. Fe caused no adverse effects on cardiac function at 3 weeks. At 6 weeks, significant declines in left ventricular (LV) ejection fraction (14.6% lower), and fractional shortening (19.6% lower) occurred in the Fe-treated control, but not in KO. Prolonging Fe treatment (8 weeks) maintained the depressed LV systolic function with a trend towards diastolic dysfunction (15.2% lower mitral valve E/A ratio) in controls but produced no impact on the KO. Fe-treatment (8 weeks) caused comparable cardiac Fe accumulation in both strains, but a 3.3-fold elevated plasma 8-isoprostane, and heightened CD11b+ staining in controls. In KO mice, lipid peroxidation and CD11b+ infiltration were 50% and 68% lower, respectively. Thus, gp91phox KO mice were significantly protected against oxidative stress, and systolic and diastolic dysfunction, supporting an important role of NOX2-mediated oxidative stress in causing cardiac dysfunction during Fe overload.

show abstract

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

Mak

Kramer

Chmielinska

et al. 2020

Hearts

View full text Add to dashboard Cite

show abstract

“… 17 – 19 As DFX can cause renal toxicity and proteinuria, creatinine should be monitored twice prior to the initiation of therapy and monthly thereafter. 9 , 10 …”

Section: Discussionmentioning

confidence: 99%

“…However, the new formulation is more bioavailable than the original Exjade ® , and the peak serum concentrations (Cmax) is approximately 30% higher. 9 , 10 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Jadenu® Substituting Exjade® in Iron Overloaded Β- Thalassemia Major (Btm) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles

Yassin

Soliman

Sanctis³

et al. 2018

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

IntroductionDue to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with β-thalassemia major (BMT). The aim of this study was to evaluate the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload.Patients and MethodsTwelve selected adult patients BMT (mean age: 29 years; range:15–34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14–28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed.ResultsApart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters.ConclusionsOur study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.

show abstract

Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review

Nashwan,

Abuawwad,

Jaradat

et al. 2024

Health Science Reports

View full text Add to dashboard Cite

Background and AimsChronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) are susceptible to complications, including iron overload, which can significantly impact their prognosis and overall health. This scoping review aimed to study the prevalence and implications of iron overload in CKD patients undergoing PD.MethodsA comprehensive search was conducted across five databases, leading to the selection of 18 papers for in‐depth analysis. These studies collectively involved 381 PD patients, 60.3% were males.ResultsNo consensus was reached regarding the exact diagnostic cutoff for iron overload. The investigations revealed four main aspects: (1) Seven papers identified various factors contributing to iron overload, emphasizing the role of different iron supplements and magnetic resonance imaging's capability to diagnose iron accumulation in organs; (2) Iron overload in young patients was found to hinder growth; (3) Six studies highlighted the adverse effects of iron overload, with cardiac issues being the most significant; (4) Three studies demonstrated the efficacy of iron‐chelating agents, Deferoxamine and Deferasirox, in treating iron overload patients undergoing PD. Overall, the estimated prevalence of liver iron overload in CKD patients on PD ranges from approximately 10% to 28.6%, which is far lower than the prevalence of 75% elegantly shown in HD patients.ConclusionWhile iron overload was a significant concern for CKD patients undergoing PD in the past, it is less common in the current era due to advancements in treatments, such as erythropoiesis‐stimulating agents. Treatment with specific chelation agents has proven beneficial, but there is also a risk of adverse effects, necessitating meticulous monitoring and timely intervention.

show abstract

Advances in iron chelation therapy: transitioning to a new oral formulation

Cited by 30 publications

References 44 publications

Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

Jadenu® Substituting Exjade® in Iron Overloaded Β- Thalassemia Major (Btm) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles

Prevalence of iron overload in patients with chronic kidney disease on peritoneal dialysis: A scoping review

Contact Info

Product

Resources

About