Safety Profiles of Iron Chelators in Young Patients with Haemoglobinopathies

BACKGROUND: This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), and combined therapy in young patients less than 25 years of age with haemoglobinopathies. METHOD: 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 2,040 patients from 34 studies were included. 92 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 corresponds 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 is scarce, but it seems equally safe compared to monotherapy. This article is protected by copyright. All rights reserved

Serious adverse drug events during deferiprone therapy in paediatric thalassaemia Patients

Conference Theme: Applying pharmacoepidemiology to improve health care in AsiaOral Presentation - Paediatrics – Mental and General HealthAim/Objective: Iron-chelation therapy is essential for transfusion-dependent thalassaemia patients. Children are particularly affected by this disease and require early chelation therapy to avoid the long term effects of iron overload. Knowledge on the incidence and nature of serious adverse drug events (e.g. neutropenia, agranulocytosis) that may lead to treatment termination is of importance in this lifelong therapy. Methods: The Hong Kong Clinical Data Analysis and Reporting System (CDARS) comprising data of more than 7 million patients was used to extract all thalassaemia patients who were receiving deferiprone below the age of 18 years. Adverse drug events (ADE) were identifi ed using a selected list of ICD-9 codes and laboratory data. All identifi ed events were assessed for causality by reviewing concomitant medications, diagnoses and laboratory data. Results: 93 patients were eligible for analysis; median age was 14 years (IQR 12-16). Median duration of deferiprone therapy was 18 months (IQR 7-32). 17 patients received monotherapy and 76 combination therapy with deferoxamine. Overall incidence rates for neutropenia, agranulocytosis, elevated liver enzymes and arthropathies were 9.7%, 5.4%, 8.6% and 3.2%; in patients with monotherapy 5.9%, 0%, 17.6% and 5.9% and with combination therapy 10.5%, 7.9%, 6.6% and 2.6%, respectively. 10 patients stopped deferiprone therapy during observation; 5, 3 and 2 patients due to agranulocytosis, arthropathies and elevated liver enzymes, respectively. 48.3% of these ADEs occurred during the fi rst 3 months of therapy. Conclusion: Combination therapy seems to be more prone for serious ADEs than monotherapy. This association must be further investigated in larger cohorts and clinical settings in paediatric patients