Botzenhardt Sebastian, Sing Chor W, Wong Ian C K, Chan Godfrey Chi-Fung, Wong Lisa Y L, Felisi Mariagrazia, Rascher Wolfgang, Ceci Adriana, Neubert Antje
Research Department of Practice & Policy, University College London, School of Pharmacy, 29-39 Brunswick Square, London, UK.
Curr Drug Saf. 2016;11(2):137-44. doi: 10.2174/1574886310666150930113957.
There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal.
• Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.
对于口服铁螯合剂去铁酮治疗依赖输血的中国儿童严重药物不良反应（ADR）的发生率，人们了解不足。在这项基于人群的回顾性队列研究中，通过诊断编码、实验室数据和住院情况，对香港的小儿地中海贫血患者进行筛查，以确定与去铁酮治疗相关的严重且具有医学重要性的不良事件。通过回顾合并用药、诊断和实验室数据评估潜在的ADR，并使用标准化因果关系评估进行评价。纳入了87例患者，共169.8人年。在21例患者中识别出30例ADR。大多数ADR（56.0%）发生在治疗的前三个月。11例患者出现中性粒细胞减少（12.6%；发病率为每100患者年6.5例），5例患者出现严重中性粒细胞减少（粒细胞缺乏症）（5.7%，发病率为每100患者年2.9例）。其他已识别的ADR包括严重关节病、肝酶升高和轻度血小板减少。总之，去铁酮治疗依赖输血的中国儿童的安全性与先前对非中国儿童的研究一致。然而，与先前研究不同的是，我们观察到联合治疗患者中粒细胞缺乏症和中性粒细胞减少症的发生率相对较高。因此，建议对接受联合铁螯合治疗的中国儿童密切监测白细胞计数。需要进一步进行前瞻性临床和药物遗传学研究，以更好地评估这一重要的安全信号。
• 与去铁酮治疗相关的已识别ADR中有一半发生在治疗的前三个月。• 粒细胞缺乏症和中性粒细胞减少症的发生率相对较高。因此，建议对接受联合铁螯合治疗的中国儿童密切监测白细胞计数。
