Botzenhardt Sebastian, Li Niya, Chan Esther W, Sing Chor Wing, Wong Ian C K, Neubert Antje
Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, University of Hong Kong, Hong Kong, China.
Eur J Haematol. 2017 Mar;98(3):198-217. doi: 10.1111/ejh.12833. Epub 2017 Jan 19.
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.
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.
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.
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.
本综述描述了去铁胺（DFO）、地拉罗司（DFP）、地拉罗司（DFX）及联合疗法在25岁以下血红蛋白病年轻患者中的安全性。
检索电子文献数据库。纳入报告铁螯合疗法相关不良事件的研究。使用美国医疗保健研究与质量局（AHRQ）偏倚风险评估工具和麦克马斯特伤害质量评估量表评估研究及报告质量。前瞻性临床研究纳入比例的随机效应荟萃分析。
纳入34项研究中2040例患者的安全性数据。识别出246例患者的92篇病例报告。DFX（937例患者）和DFP（667例患者）有最大量已发表的安全性证据。联合治疗方案的研究较少。所有治疗方案均可见转氨酶升高（3.9% - 31.3%），DFP和DFX可见胃肠道疾病（分别为3.7% - 18.4%和5.8% - 18.8%）。因不良事件停药率较低（0 - 4.1%）。大多数研究的报告质量存在选择性且较差。
铁螯合疗法在年轻患者中总体安全，已发表数据与产品特性总结相符。每种铁螯合治疗方案都有其特定的安全风险。DFO在推荐剂量下似乎与严重不良反应无关。在DFP和DFX中，可能发生罕见但严重的不良反应。联合治疗的数据较少，但与单药治疗相比似乎同样安全。
