Intravenous Iron-Carbohydrate Nanoparticles and Their Similars. What Do We Choose?

Abstract

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).

TABLE 1.

Benefits of iron therapy in different conditions

FIGURE 1.

Serum ferritin and iron-carbohydrate complexes have similar structure [adapted from (86)]

TABLE 2.

Intravenous iron formulations [adapted from (85)]

TABLE 3.

Characteristics of small molecules, biologics and non-biologic complex drugs [adapted from (106)]

TABLE 4.

Potential disadvantages of iron sucrose nanosimilars