Mehedinti Ana Maria, Capusa Cristina, Andreiana Iuliana, Mircescu Gabriel
"Carol Davila" University of Medicine and Pharmacy, Nephrology Department, Bucharest, Romania.
Maedica (Bucur). 2022 Jun;17(2):436-448. doi: 10.26574/maedica.2022.17.2.436.
Anemia is highly prevalent worldwide and iron deficiency is the first cause. Iron deficiency has not only hematologic effects but also non-hematologic effects - immune, metabolic, cognitive dysfunctions and poor cardiovascular and renal outcomes - which generally precede anemia. Iron therapy not only significantly improves the hematological parameters but also has non-hematologic benefits. Given that its efficacy and safety has been revealed over the years, intravenous (IV) iron therapy is frequently used. Intravenous iron products are nanoparticles largely consisting in an iron core surrounded by a carbohydrate shell. They are classified as non-biological complex molecules, being different from small commonly used molecules, with properties and biological behavior impossible to be completely characterized only by physicochemical analysis. To date, there is no appropriate regulatory evaluation system for these medicines and several follow-on versions of the IV iron originators (e.g., iron sucrose) were approved using the same regulatory pathway as for generics. Because of this vulnerability in an adequate pathway for approval, both non-clinical and clinical studies suggested no therapeutic equivalence (thus no interchangeability) between iron sucrose originator (Venofer®), and iron sucrose similars. In this review we aimed to underline the importance of intravenous iron therapy as well as raise awareness regarding the differences between nanomedicines and their intended similar but not identical copies. The potential implications of these differences impact patients (safety, efficacy) but also the medical system (higher costs).
贫血在全球范围内高度流行，缺铁是首要原因。缺铁不仅会产生血液学影响，还会带来非血液学影响——免疫、代谢、认知功能障碍以及不良的心血管和肾脏后果，这些通常先于贫血出现。铁疗法不仅能显著改善血液学参数，还具有非血液学益处。鉴于多年来已证实其疗效和安全性，静脉注射（IV）铁疗法被频繁使用。静脉铁剂产品是纳米颗粒，主要由被碳水化合物外壳包围的铁核组成。它们被归类为非生物复合分子，与常用的小分子不同，其性质和生物学行为无法仅通过物理化学分析完全表征。迄今为止，对于这些药物尚无适当的监管评估系统，静脉铁剂原创药（如蔗糖铁）的几种后续版本是按照与仿制药相同的监管途径获批的。由于在适当的审批途径方面存在这种漏洞，非临床和临床研究均表明蔗糖铁原创药（Venofer®）与蔗糖铁类似物之间不存在治疗等效性（因此不存在可互换性）。在本综述中，我们旨在强调静脉铁疗法的重要性，并提高对纳米药物与其预期的相似但不相同仿制品之间差异的认识。这些差异的潜在影响不仅涉及患者（安全性、疗效），还涉及医疗系统（更高成本）。
