Bailie George R, Hörl Walter H, Verhoef Jan-Jaap
Albany Nephrology Pharmacy Group, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA.
Arzneimittelforschung. 2011;61(5):267-75. doi: 10.1055/s-0031-1296198.
Spontaneously-reported rates of adverse events (AEs) of intravenous (i.v.) iron products have not been compared since 2007. AEs in Europe (Eur) and North America (NA) have never been compared. New products have been marketed and many changes in prescribing habits have occurred since then, and the effect on AEs reporting is unclear. It was hypothesized that changing practices for i.v. iron products has caused changes in the rates of serious AEs and large differences exist between Eur and NA. Rates of AEs for three i.v. iron preparations (iron sucrose [IS], ferric gluconate [FG] and high and low MW iron dextran [HMWID, LMWID]) were compared by product and continent from January 1, 2003 to June 30, 2009 for selected countries in Eur and NA, using the Uppsala Monitoring Center's database. Rates of total, anaphylaxis and other serious allergic AEs were calculated as number of AEs divided by i.v. iron sales standardized to 100 mg dose equivalents (DEq) of iron. Quarterly sales (millions of 100 mg DEq of iron) increased from the first quarter 2003 to the end of the second quarter of 2009 by 1% for FG, 16% for IS and 2% for ID. Total AEs for NA plus Eur were similar for FG and IS, but total AEs were 6- to 7-fold higher for ID. Rates of anaphylaxis were 6- to 11-fold higher in Eur plus NA combined for ID than for IS or FG. In NA, there were substantially higher reports for total, anaphylaxis and other serious allergic AEs with FG compared to IS, whereas the reverse was the case in Eur. Odds ratios (OR) showed higher risks of anaphylaxis with FG in NA vs. Eur (OR = 4.40, P < 0.0001) and lower risks with IS (OR = 0.24, P < 0.0001). Odds of anaphylaxis with LMWID in Eur vs. FG and IS were 42.08 and 16.92 (both P < 0.0001), respectively. In NA, odds of anaphylaxis with ID vs. FG and IS were 2.36 and 17.73 (both P < 0.0001), respectively. Differences between NA and Eur may be related to varied treatment practices. ID had the highest rates of all types of AEs, and IS and FG had a continued trend for lowest rates of AEs.
自2007年以来，尚未对静脉注射铁剂产品的不良事件（AE）自发报告率进行比较。欧洲（Eur）和北美（NA）的不良事件从未进行过比较。从那时起，新产品已上市，处方习惯也发生了许多变化，而这些变化对不良事件报告的影响尚不清楚。据推测，静脉注射铁剂产品使用方式的改变已导致严重不良事件发生率发生变化，且欧洲和北美之间存在很大差异。利用乌普萨拉监测中心的数据库，对2003年1月1日至2009年6月30日期间欧洲和北美部分国家三种静脉注射铁剂制剂（蔗糖铁[IS]、葡萄糖酸铁[FG]以及高、低分子量右旋糖酐铁[HMWID、LMWID]）的不良事件发生率按产品和地区进行了比较。将总不良事件、过敏反应及其他严重过敏不良事件的发生率计算为不良事件数量除以经标准化至100mg铁剂量当量（DEq）的静脉注射铁剂销售量。从2003年第一季度到2009年第二季度末，葡萄糖酸铁的季度销售量（以100mg铁DEq计，单位：百万）增长了1%，蔗糖铁增长了16%，右旋糖酐铁增长了2%。北美和欧洲葡萄糖酸铁与蔗糖铁的总不良事件发生率相似，但右旋糖酐铁的总不良事件发生率高出6至7倍。欧洲和北美合计，右旋糖酐铁的过敏反应发生率比蔗糖铁或葡萄糖酸铁高出6至11倍。在北美，葡萄糖酸铁的总不良事件、过敏反应及其他严重过敏不良事件报告显著多于蔗糖铁，而在欧洲情况则相反。比值比（OR）显示，北美葡萄糖酸铁发生过敏反应的风险高于欧洲（OR = 4.40，P < 0.0001），而蔗糖铁的风险较低（OR = 0.24，P < 0.0001）。欧洲低分子量右旋糖酐铁与葡萄糖酸铁和蔗糖铁相比，发生过敏反应的比值分别为42.08和16.92（P均< 0.0001）。在北美，右旋糖酐铁与葡萄糖酸铁和蔗糖铁相比，发生过敏反应的比值分别为2.36和17.73（P均< 0.0001）。北美和欧洲之间的差异可能与不同的治疗方式有关。右旋糖酐铁各类不良事件的发生率最高，而蔗糖铁和葡萄糖酸铁的不良事件发生率持续呈最低趋势。
