A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer®), a new intravenous iron preparation and its clinical implications

Abstract

The treatment of iron deficiency anemia with polynuclear iron formulations is an established therapy in patients with chronic kidney disease but also in other disease areas like gastroenterology, cardiology, oncology, pre/post operatively and obstetrics’ and gynecology. Parenteral iron formulations represent colloidal systems in the lower nanometer size range which have traditionally been shown to consist of an iron core surrounded by a carbohydrate shell. In this publication, we for the first time describe the novel matrix structure of iron isomaltoside 1000 which differs from the traditional picture of an iron core surrounded by a carbohydrate. Despite some structural similarities between the different iron formulations, the products differ significantly in their physicochemical properties such as particle size, zeta potential, free and labile iron content, and release of iron in serum. This study compares the physiochemical properties of iron isomaltoside 1000 (Monofer®) with the currently available intravenous iron preparations and relates them to their biopharmaceutical properties and their approved clinical applications. The investigated products encompass low molecular weight iron dextran (CosmoFer®), sodium ferric gluconate (Ferrlecit®), iron sucrose (Venofer®), iron carboxymaltose (Ferinject®/Injectafer®), and ferumoxytol (Feraheme®) which are compared to iron isomaltoside 1000 (Monofer®). It is shown that significant and clinically relevant differences exist between sodium ferric gluconate and iron sucrose as labile iron formulations and iron dextran, iron carboxymaltose, ferumoxytol, and iron isomaltoside 1000 as stable polynuclear formulations. The differences exist in terms of their immunogenic potential, safety, and convenience of use, the latter being expressed by the opportunity for high single-dose administration and short infusion times. Monofer is a new parenteral iron product with a very low immunogenic potential and a very low content of labile and free iron. This enables Monofer, as the only IV iron formulation, to be administered as a rapid high dose infusion in doses exceeding 1000 mg without the application of a test dose. This offers considerable dose flexibility, including the possibility of providing full iron repletion in a single infusion (one-dose iron repletion).