Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.
Christian Doppler Laboratory of Iron and Phosphate Biology, Medical University of Innsbruck, Innsbruck, Austria.
Br J Clin Pharmacol. 2021 May;87(5):2256-2273. doi: 10.1111/bcp.14643. Epub 2020 Dec 7.
Hypophosphataemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. The aim of this study was to determine frequency, severity, duration and risk factors of incident hypophosphataemia after treatment with FCM and IIM.
A systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005-2020 was carried out using the search terms 'ferric carboxymaltose' OR 'iron isomaltoside'. Prospective clinical trials reporting outcomes on hypophosphataemia rate, mean nadir serum phosphate and/or change in mean serum phosphate from baseline were selected. Hypophosphataemia rate and severity were compared for studies on IIM vs. FCM after stratification for chronic kidney disease. Meta-regression analysis was used to investigate risk factors for hypophosphataemia.
Across the 42 clinical trials included in the meta-analysis, FCM induced a significantly higher incidence of hypophosphataemia than IIM (47%, 95% CI 36-58% vs. 4%, 95% CI 2-5%), and significantly greater mean decreases in serum phosphate (0.40 vs. 0.06 mmol/L). Hypophosphataemia persisted at the end of the study periods (maximum 3 months) in up to 45% of patients treated with FCM. Meta-regression analysis identified low baseline serum ferritin and transferrin saturation, and normal kidney function as significant predictors of hypophosphataemia.
FCM is associated with a high risk of hypophosphataemia, which does not resolve for at least 3 months in a large proportion of affected patients. More severe iron deficiency and normal kidney function are risk factors for hypophosphataemia.
低磷血症是越来越多的铁羧麦芽糖（FCM）和可能的异麦芽糖铁/铁去异麦芽糖（IIM）治疗缺铁的副作用，这两种药物都用于治疗缺铁。本研究的目的是确定 FCM 和 IIM 治疗后发生低磷血症的频率、严重程度、持续时间和危险因素。
使用“ferric carboxymaltose”或“iron isomaltoside”在 EMBASE、PubMed 和 Web of Science 中进行了 2005 年至 2020 年的文献系统检索。选择报告低磷血症发生率、血清磷酸盐最低值和/或基线时血清磷酸盐平均值变化的前瞻性临床试验。对慢性肾脏病分层的 IIM 与 FCM 的研究进行低磷血症发生率和严重程度的比较。使用Meta 回归分析来研究低磷血症的危险因素。
在纳入的 42 项临床试验的meta 分析中，FCM 诱导的低磷血症发生率明显高于 IIM（47%，95%CI 36-58%比 4%，95%CI 2-5%），且血清磷酸盐的平均下降幅度明显更大（0.40 比 0.06mmol/L）。在接受 FCM 治疗的患者中，高达 45%的患者在研究结束时（最长 3 个月）仍存在低磷血症。Meta 回归分析确定低基线血清铁蛋白和转铁蛋白饱和度以及正常肾功能是低磷血症的显著预测因素。
FCM 与高风险的低磷血症相关，在很大一部分受影响的患者中，低磷血症至少在 3 个月内无法解决。更严重的缺铁和正常肾功能是低磷血症的危险因素。
