Adverse effects of oral chelators in thalassemia major patients

Thalassemia major (TM) is a hereditary hemolytic anemia due to the decreased or impaired biosynthesis of β-globin chain. Erythrocyte transfusion is needed to ameliorate anemia. These repeated blood transfusions cause severe iron overload in the patients' tissues so iron chelation is needed to reduce iron overload. Although iron chelation therapy is one of the important parameters affecting mortality and morbidity in beta thalassemia major patients, these chelators can cause some adverse effects. It is important to follow patients taking iron chelation therapy regularly to protect body from complication caused by adverse effects of the chelators. In this study, we aimed to search adverse effects occurred as a result of usage of deferiprone (DFP) and deferasirox (DFS) iron chelators in thalassemia major patients followed in Pediatric Hematology Department at Akdeniz University Hospital. Thalassemia major patients followed in Pediatric Hematology Department at Akdeniz University Hospital were evaluated retrospectively. Totally 197 (102 girls and 95 boys) patients using deferiprone (n:100) and deferasirox (n:97) followed between May 2004 –December 2013 were included the study. Adverse events were determined in 59 cases (35 DFP and 24 DFS). The age of the patients were between 4 and 39 years old, mean age was 16,88. The frequency of the adverse effects of deferiprone usage were neutropenia in 14% patients, gastrointestinal system (GIS) adverse effects in 13%, arthritis/arthralgia in 5%, elevated transaminases in 2% and headache in 1%. Neutropenia as an adverse effect in DFP using patients was significantly higher than DFS using patients (p<0,05). The dose of DFP when adverse effects occurred was between 23 mg/kg/ day and 105 mg/kg/day, and mean dose was 65,6 mg/kg/day. Also, in 10 patients using DFP, adverse effects were occurred at subtherapeutic dose (under 75 mg/kg/day). The lowest subtherapeutic drug doses caused adverse effects were seen in patients with GIS adverse effect however drug tolerance developed in a short time. The frequency of the adverse effects of deferasirox usage were proteinuria in 5,15% patiens, rash in 4,12%, cataract in 4,12%, GIS adverse event in 4,12%, elevated transaminase in 3,09%, Neutropenia in 1,03%, headache in 1,03.%, hyperglycemia in 1,03.%, hearing loss in 1,03.%. In this study it was indicated that the frequency of proteinuria, rash and cataract in patients using DFS were significantly higher than patients using DFP (p<0,05). The dose of defarasirox when adverse effects occurred was between 10 mg/kg/ day and 40 mg/kg/day, and mean dose was 65,6 mg/kg/ day. Adverse effect was occurred at subtherapeutic dose (under 20 mg/kg/day) in only one patient using deferasirox. This adverse effect was cataract occurred at a dose of 10 mg/kg/day. In our study, the frequency of neutropenia in DFP group was higher than that frequency indicated in literature. The frequency of GIS adverse effects was similar to frequency indicated in literature. It was seen that GIS adverse effect can be occurred even at low doses of drug however tolerability develop in a short time. Incidence of arthritis/arthralgia in the study was lower than the incidence indicated in literature and complaints were diminished when dose reduced by time. Also, in this study avascular necrosis in talus bone, bone marrow edema and soft tissue edema were observed in 2% of patients and as far as we searched these findings have not be reported in the literature yet. In this study frequency of cataract in thalassemia major patients using deferasirox was higher than frequency indicated in literature. The frequencies of proteinuria, GIS adverse effects, elevated transaminase, rash, neutropenia, hyperglycemia, hearing loss and headache were similar to the frequencies reported in the literature. As a result, for side effects regular and multidisciplinary follow up of patients using chelating treatment is important, so close monitoring of patients can protect them from adverse effects and their complications