Division of Clinical Pharmacology & Toxicology, University Hospital Basel, Schanzenstrasse 55, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, University of Basel, St. Johanns-Vorstadt 27, 4031 Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Spitalstrasse 26, 4031 Basel, Switzerland.
Eur J Intern Med. 2019 Oct;68:36-43. doi: 10.1016/j.ejim.2019.07.029. Epub 2019 Aug 3.
Reports of metamizole-induced neutropenia have increased in Switzerland and Germany over the last decades, most likely reflecting increased use of metamizole. To date, there are no effective strategies to identify patients at increased risk of metamizole-induced neutropenia. In this observational, multi-center comparative study, characteristics of patients with metamizole-associated neutropenia were compared with patients treated with metamizole without developing adverse hematological reactions. Patients with metamizole-induced neutropenia treated at the University Hospitals Basel and Bern between 2005 and 2017 were included. Tolerant comparison patients with continuous metamizole treatment (≥500 mg/day for at least 28 days) were recruited from GP offices and community pharmacies. Forty-eight patients with metamizole-induced neutropenia, consisting of 23 and 25 cases with inpatient-acquired and outpatient-acquired neutropenia, respectively, were compared to 39 metamizole tolerant comparison patients. Median latency until first diagnosis of neutropenia was 6 days (1-61 days) in inpatient cases and 19 days (2-204 days) in outpatient cases. There was no association between non-myelotoxic and non-immunosuppressive co-medication (p = .6627), history of drug allergy (p = .1304), and preexisting auto-immune diseases (p = .2313) and the development of metamizole-induced neutropenia. Our results suggest that autoimmune diseases, history of drug allergy, and concomitant treatment with non-myelotoxic and non-immunosuppressive drugs are likely not individual risk factors for metamizole-associated neutropenia.
在过去几十年中，瑞士和德国的报道称，使用麦角胺引起的中性粒细胞减少症有所增加，这很可能反映了麦角胺使用的增加。迄今为止，尚无有效的策略可以确定易发生麦角胺引起的中性粒细胞减少症的患者。在这项观察性、多中心比较研究中，比较了麦角胺相关性中性粒细胞减少症患者与未发生不良血液学反应的麦角胺治疗患者的特征。在 2005 年至 2017 年间，巴塞尔和伯尔尼大学医院收治了麦角胺诱导性中性粒细胞减少症的患者。从全科医生办公室和社区药房招募了接受连续麦角胺治疗（至少 500mg/天，至少 28 天）的耐麦角胺比较患者。将 48 例麦角胺诱导性中性粒细胞减少症患者（分别为 23 例和 25 例分别为住院获得性和门诊获得性中性粒细胞减少症）与 39 例麦角胺耐受比较患者进行比较。住院中性粒细胞减少症患者的潜伏期中位数为 6 天（1-61 天），门诊中性粒细胞减少症患者的潜伏期中位数为 19 天（2-204 天）。非骨髓毒性和非免疫抑制性联合用药（p=0.6627）、药物过敏史（p=0.1304）和自身免疫性疾病史（p=0.2313）与麦角胺诱导的中性粒细胞减少症的发生之间没有关联。我们的结果表明，自身免疫性疾病、药物过敏史和非骨髓毒性和非免疫抑制性药物的联合治疗可能不是麦角胺相关性中性粒细胞减少症的个体危险因素。
