Huber Matthias, Andersohn Frank, Bronder Elisabeth, Klimpel Andreas, Thomae Michael, Konzen Christine, Meyer Oliver, Salama Abdulgabar, Schrezenmeier Hubert, Hildebrandt Martin, Späth-Schwalbe Ernst, Grüneisen Andreas, Kreutz Reinhold, Garbe Edeltraut
Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Eur J Clin Pharmacol. 2014 Mar;70(3):339-45. doi: 10.1007/s00228-013-1618-1. Epub 2013 Dec 3.
Drug-induced agranulocytosis (DIAG) is a rare but serious adverse drug reaction. The Berlin Case-Control Surveillance Study (FAKOS) aimed to identify pharmaceuticals with an increased risk for this condition.
Adult patients with acute non-chemotherapy-induced agranulocytosis, developed in hospital or in the outpatient setting, were ascertained by active surveillance in all 51 Berlin hospitals between the years 2000 and 2010. Applying the criteria of the World Health Organization, a standardized drug causality assessment was conducted for each agranulocytosis patient to determine possible drug aetiology. Drug risks were quantified in a case-control design with unconditional logistic regression analysis.
Sixty-three out of 88 validated cases of agranulocytosis were identified as being at least probably drug-related. Drug causality assessment resulted in 36 pharmaceuticals with a certain or probable relationship to agranulocytosis. Drugs involved in ≥ 3 cases with a probable or certain causality were metamizole (dipyrone) (N = 10), clozapine (N = 6), sulfasalazine (N = 5), thiamazole (N = 5), and carbamazepine (N = 3). In case-control analysis, six drugs were identified with significant odds ratios for DIAG. The highest odds ratios were observed for clozapine, sulfasalazine, and thiamazole.
Our findings are generally in agreement with those of earlier case-control studies. The spectrum of drugs causing acute agranulocytosis has not changed considerably over recent years, despite many newly marketed drugs. Evidence for induction of agranulocytosis by some new pharmaceuticals is supported.
药物性粒细胞缺乏症（DIAG）是一种罕见但严重的药物不良反应。柏林病例对照监测研究（FAKOS）旨在识别具有这种情况风险增加的药物。
2000年至2010年间，通过对柏林所有51家医院的主动监测，确定了在医院或门诊环境中发生的急性非化疗引起的粒细胞缺乏症的成年患者。根据世界卫生组织的标准，对每位粒细胞缺乏症患者进行标准化的药物因果关系评估，以确定可能的药物病因。在病例对照设计中，采用无条件逻辑回归分析对药物风险进行量化。
88例经证实的粒细胞缺乏症病例中，有63例被确定至少可能与药物有关。药物因果关系评估结果显示，有36种药物与粒细胞缺乏症有确定或可能的关系。因果关系可能或确定且涉及≥3例病例的药物有安乃近（N = 10）、氯氮平（N = 6）、柳氮磺胺吡啶（N = 5）、甲巯咪唑（N = 5）和卡马西平（N = 3）。在病例对照分析中，确定了6种药物的DIAG比值比有统计学意义。氯氮平、柳氮磺胺吡啶和甲巯咪唑的比值比最高。
我们的研究结果总体上与早期病例对照研究的结果一致。尽管有许多新药上市，但近年来导致急性粒细胞缺乏症的药物谱没有太大变化。一些新药诱发粒细胞缺乏症的证据得到了支持。
