The Southern Network on Adverse Reactions (SONAR) Program, University of South Carolina College of Pharmacy, Columbia, SC.
Department of Medicine, William Jennings Bryan Dorn Veterans Administration Medical Center, Columbia, SC.
Am J Ther. 2018 Nov/Dec;25(6):e670-e674. doi: 10.1097/MJT.0000000000000768.
Unexpected serious adverse drug reactions (sADRs) affecting patients with chronic kidney disease (CKD) who received erythropoiesis-stimulating agents were identified by study co-authors. These included pure red cell aplasia (PRCA) after administration of the Eprex formulation of epoetin or the epoetin biosimilar HX575 and fatal anaphylaxis associated with peginesatide, an erythropoietin receptor agonist. We developed and applied a structured framework to describe these sADRs, including root cause analyses and eradication efforts.
A 10-step framework termed "ANTICIPATE," focusing on signal identification, incidence, causality, and eradication guided our evaluations.
Initial cases were identified by a hematologist (Eprex), clinical study monitors (HX575), and 4 nurses (peginesatide). The number of persons with individual ADRs was 13 PRCA cases for epoetin, 2 antibody-mediated PRCA cases for HX575, and 5 fatal anaphylaxis cases for peginesatide. Initial incidence estimates per 1000 treated persons were 0.27 for Eprex-associated PRCA, 11 for HX575-associated PRCA, and 0.38 for peginesatide fatalities. Likely causes were subcutaneous administration of epoetin formulated with polysorbate 80 (Eprex), tungsten leaching from pins included in product syringes (HX575), and inclusion of a phenol stabilizer (peginesatide). Eradication strategies included restricting Eprex administration to the intravenous route, excluding tungsten from HX575 syringes, and for peginesatide, proposed eradication was to return to single-dose vials without preservatives.
Although the number of cases of each sADR was small, eradication was successful for 2 sADRs, and a proposed eradication was developed for a third sADR. The structured framework used to describe the above 3 sADRs in patients with CKD can also be used in other clinical settings.
研究合著者发现，接受促红细胞生成素刺激剂治疗的慢性肾脏病（CKD）患者出现了意外的严重药物不良反应（sADR），包括依泊汀制剂或依泊汀生物类似物 HX575 给药后发生纯红细胞再生障碍性贫血（PRCA），以及培塞利肽（一种促红细胞生成素受体激动剂）相关的致命过敏反应。我们开发并应用了一个结构化框架来描述这些 sADR，包括根本原因分析和根除措施。
一个名为“ANTICIPATE”的 10 步框架，侧重于信号识别、发生率、因果关系和根除，指导了我们的评估。
最初的病例是由一名血液学家（Eprex）、临床研究监测员（HX575）和 4 名护士（培塞利肽）发现的。出现个别 ADR 的人数为 13 例依泊汀相关 PRCA、2 例 HX575 相关抗体介导 PRCA 和 5 例培塞利肽致命过敏反应。每 1000 名治疗患者的初始发生率估计值分别为 Eprex 相关 PRCA 为 0.27，HX575 相关 PRCA 为 11，培塞利肽死亡率为 0.38。可能的原因是含有聚山梨醇 80 的依泊汀（Eprex）皮下给药、产品注射器中含有的钨浸出（HX575）以及包含苯酚稳定剂（培塞利肽）。根除策略包括将依泊汀限制为静脉途径给药、从 HX575 注射器中排除钨以及对于培塞利肽，建议的根除方法是恢复不含防腐剂的单剂量小瓶。
尽管每个 sADR 的病例数量较少，但对于 2 个 sADR 已成功根除，对于第 3 个 sADR 提出了根除建议。用于描述 CKD 患者上述 3 个 sADR 的结构化框架也可用于其他临床环境。
