Experience with the oral iron chelator deferiprone in transfusion-dependent children

Lucas, Gérard; Perera, Bjc; Fonseka, E A N; Silva, D D S De; Fernandopulle, M; Karunatilaka, D.H.; Weerasinghe, Irangani

doi:10.4038/cmj.v47i4.3413

Cited by 13 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other side effects like hepatitis, radiographic skeletal changes and growth retardation were not assessed. Side effect profile of deferiprone 14,15,16 was similar to previous studies but there were only 10 patients on deferiprone. A literature survey did not reveal any previous studies done in Sri Lanka regarding side effect profile of desferrioxamine, hence we compared with a periodical 17 and the profile of our patients was found to be similar.…”

Section: Discussionsupporting

confidence: 83%

A clinical audit of thalassaemia management at the Lady Ridgeway Hospital for Children, Colombo

Samarakoon¹,

Wijesuriya²

2011

Sri Lanka J Child Health

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 83%

A clinical audit of thalassaemia management at the Lady Ridgeway Hospital for Children, Colombo

Samarakoon¹,

Wijesuriya²

2011

Sri Lanka J Child Health

View full text Add to dashboard Cite

show abstract

“…Published data on the use of DFP in SCD are sparse and derive from small series of patients with a variety of underlying diseases. These results, though usually not analysed by disease, show that the efficacy and tolerability of DFP in SCD were similar to those in patients with thalassaemia (Lucas et al , ; El‐Alfy et al , ).…”

Section: Managing Iron Chelation In Children With Sickle Cell Diseasesupporting

confidence: 64%

Current approach to iron chelation in children

2014

View full text Add to dashboard Cite

SummaryTransfusion-dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non-transfusiondependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron-induced end-organ complications, in order to achieve a normal pattern of complication-free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores' depletion.

show abstract

“…Our original concerns about deferiprone-associated liver toxicity [10] were dismissed [27, 28, 39] [110]; the incidence of deferiprone-associated ALT elevations was subsequently estimated as 7.5% [111]. However, most studies in the literature have failed to report ALT changes, or reported lack of changes after short-term exposures, or in selected patients only [10, 18, 44–47, 49, 51, 52, 56, 58, 62, 66–72, 86, 87, 112–114]. One large study recorded ALT surges 3-fold over baseline in 20% of patients [52]; another reported a 4-fold greater mean ALT elevation in deferiprone-exposed patients, than during deferoxamine, but claimed this to be not significantly different [25].…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, the FDA observed that this observation might “signal[s] the potential for deferiprone induced liver toxicity." Often, “transient” ALT elevations [43, 48, 54, 59] have been later acknowledged as sustained: [51, 59, 60] the Apotex “safety” trial, for example, claimed initially that “increased ALT levels “usually stabilized or regressed after three to six months” [34], but later acknowledged mean ALT had remained significantly elevated over baseline over years [56].…”

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

Experience with the oral iron chelator deferiprone in transfusion-dependent children

Cited by 13 publications

References 0 publications

A clinical audit of thalassaemia management at the Lady Ridgeway Hospital for Children, Colombo

A clinical audit of thalassaemia management at the Lady Ridgeway Hospital for Children, Colombo

Current approach to iron chelation in children

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

Contact Info

Product

Resources

About