Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia

Botzenhardt, Sebastian; Sing, Chor‐Wing; Wong, Ian Chi Kei; Chan, Godfrey Chi-Fung; Wong, Lo; Felisi, Mariagrazia; Rascher, Wolfgang; Ceci, Adriana; Neubert, Antje

doi:10.2174/1574886310666150930113957

Cited by 7 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,8,9 Ethnic differences may influence the occurrence of agranulocytosis as reported in Chinese children on DFP. 10 Combined therapy was not associated with a higher risk for neutropenia consistent with existing data. 4 European sites reported neutropenia more often than non-European sites (13.5% vs.…”

Section: /9supporting

confidence: 84%

Long-term safety of deferiprone treatment in children from the Mediterranean region with beta-thalassemia major: the DEEP-3 multi-center observational safety study

et al. 2017

Self Cite

View full text Add to dashboard Cite

Section: /9supporting

confidence: 84%

Long-term safety of deferiprone treatment in children from the Mediterranean region with beta-thalassemia major: the DEEP-3 multi-center observational safety study

et al. 2017

Self Cite

View full text Add to dashboard Cite

“…Nonetheless, based upon a claimed ‘cardio-protective’ effect [27–29], deferiprone is prescribed worldwide as first line therapy, either as monotherapy (15%), or in regimens combining deferiprone with less-than -therapeutic doses of other drugs (25%) [30, 31]. Deferiprone is frequently prescribed as first line therapy even to children (for example, 68.3% of children in the Middle East [32], despite inadequate monitoring [33–35]). Its recommendation in pediatric practice persists despite higher rates of toxicity in children, including neutropenia (12.6%), agranulocytosis (5%) [35], and liver dysfunction [36, 37]), than were reported in the Apotex-directed “safety” study [34].…”

Section: Discussionmentioning

confidence: 99%

“…Deferiprone is frequently prescribed as first line therapy even to children (for example, 68.3% of children in the Middle East [32], despite inadequate monitoring [33–35]). Its recommendation in pediatric practice persists despite higher rates of toxicity in children, including neutropenia (12.6%), agranulocytosis (5%) [35], and liver dysfunction [36, 37]), than were reported in the Apotex-directed “safety” study [34].…”

Section: Discussionmentioning

confidence: 99%

Single-center retrospective study of the effectiveness and toxicity of the oral iron chelating drugs deferiprone and deferasirox

2019

View full text Add to dashboard Cite

Background Iron overload, resulting from blood transfusions in patients with chronic anemias, has historically been controlled with regular deferoxamine, but its parenteral requirement encouraged studies of orally-active agents, including deferasirox and deferiprone. Deferasirox, licensed by the US Food and Drug Administration in 2005 based upon the results of randomized controlled trials, is now first-line therapy worldwide. In contrast, early investigator-initiated trials of deferiprone were prematurely terminated after investigators raised safety concerns. The FDA declined market approval of deferiprone; years later, it licensed the drug as “last resort” therapy, to be prescribed only if first-line drugs had failed. We undertook to evaluate the long-term effectiveness and toxicities of deferiprone and deferasirox in one transfusion clinic. Methods and findings Under an IRB-approved study, we retrospectively inspected the electronic medical records of consented iron-loaded patients managed between 2009 and 2015 at The University Health Network (UHN), Toronto. We compared changes in liver and heart iron, adverse effects and other outcomes, in patients treated with deferiprone or deferasirox. Results Although deferiprone was unlicensed in Canada, one-third (n = 41) of locally-transfused patients had been switched from first-line, licensed therapies (deferoxamine or deferasirox) to regimens of unlicensed deferiprone. The primary endpoint of monitoring in iron overload, hepatic iron concentration (HIC), increased (worsened) during deferiprone monotherapy (mean 10±2–18±2 mg/g; p < 0.0003), exceeding the threshold for life-threatening complications (15 mg iron/g liver) in 50% patients. During deferasirox monotherapy, mean HIC decreased (improved) (11±1–6±1 mg/g; p < 0.0001). Follow-up HICs were significantly different following deferiprone and deferasirox monotherapies (p < 0.0000002). Addition of low-dose deferoxamine (<40 mg/kg/day) to deferiprone did not result in reductions of HIC to <15 mg/g (baseline 20±4 mg/g; follow-up, 18±4 mg/g; p < 0.2) or in reduction in the proportion of patients with HIC exceeding 15 mg/g (p < 0.2). During deferiprone exposure, new diabetes mellitus, a recognized consequence of inadequate iron control, was diagnosed in 17% patients, most of whom had sustained HICs exceeding 15 mg/g for years; one woman died after 13 months of a regimen of deferiprone and low-dose deferasirox. During deferiprone exposure, serum ALT increased over baseline in 65% patients. Mean serum ALT increased 6.6-fold (p < 0.001) often persisting for years. During deferasirox exposure, mean ALT was unchanged (p < 0.84). No significant differences between treatment groups were observed in the proportions of patients estimated to have elevated cardiac iron. Conclusions Deferiprone showed ineffectiveness and significant toxicity in most patients. Combination with low doses of first-line therapies did not improve the ...

show abstract

“…Other potential mechanisms are maturation arrest of granulocytic lineage or decreased production of granulocyte colony-forming units (98). Specific risk factors and pharmacogenetic dispositions have also not been identified yet (44,99). Our meta-analysis shows that the incidence of agranulocytosis in children and adolescents may be lower than the 0.5-0.9% reported previously (94,95).…”

Section: Deferiprone (Dfp)mentioning

confidence: 64%

“…neutropenia in the past for DFP or renal dysfunction for DFX). Furthermore, it was not always clear whether the patients were na€ ıve to iron chelation or switching from an (99,192,193) N, number of studied patients; PI, pooled incidence in per cent with 95% confidence interval; NR, not investigated and/or reported in any study publication. 1 Only one study reported this AE; if incidence is <0.001% only one decimal place is expressed (0.0%).…”

Section: Adverse Effects Reporting Qualitymentioning

confidence: 99%

Safety profiles of iron chelators in young patients with haemoglobinopathies

Botzenhardt

Chan

et al. 2017

European J of Haematology

Self Cite

View full text Add to dashboard Cite

Background: This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr of age with haemoglobinopathies. Methods: Searches in electronic literature databases were performed. Studies reporting adverse events associated with iron chelation therapy were included. Study and reporting quality was assessed using AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms. Prospective clinical studies were pooled in a random-effects meta-analysis of proportions. Results: Safety data of 2040 patients from 34 studies were included. Ninety-two case reports of 246 patients were identified. DFX (937 patients) and DFP (667 patients) possess the largest published safety evidence. Fewer studies on combination regimens are available. Increased transaminases were seen in all regimens (3.9-31.3%) and gastrointestinal disorders with DFP and DFX (3.7-18.4% and 5.8-18.8%, respectively). Therapy discontinuations due to adverse events were low (0-4.1%). Reporting quality was selective and poor in most of the studies. Conclusion: Iron chelation therapy is generally safe in young patients, and published data correspond to summary of product characteristics. Each iron chelation regimen has its specific safety risks. DFO seems not to be associated with serious adverse effects in recommended doses. In DFP and DFX, rare, but serious, adverse reactions can occur. Data on combined therapy are scarce, but it seems equally safe compared to monotherapy.

show abstract

Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia

Cited by 7 publications

References 0 publications

Long-term safety of deferiprone treatment in children from the Mediterranean region with beta-thalassemia major: the DEEP-3 multi-center observational safety study

Long-term safety of deferiprone treatment in children from the Mediterranean region with beta-thalassemia major: the DEEP-3 multi-center observational safety study

Single-center retrospective study of the effectiveness and toxicity of the oral iron chelating drugs deferiprone and deferasirox

Safety profiles of iron chelators in young patients with haemoglobinopathies

Contact Info

Product

Resources

About