Intravenous iron supplementation therapy

Intravenous infusions of iron have evolved from a poorly effective and dangerous intervention to a safe cornerstone in the treatment of iron deficiency. Modern iron formulations are composite nanoparticles composed of carbohydrate ferric oxy-hydroxides. Iron dextran, iron derisomaltose (formely known as iron isomaltoside 1000), ferric carboxymaltose, ferrumoxytol, iron sucrose and sodium ferric gluconate can be infused at different doses and allow correction of total iron deficit with single or repeated doses in 1-2 weeks depending on the specific formulation. All iron preparations are associated with a risk of severe infusion reactions. In recent prospective clinical trials, the risk of moderate to severe infusion reactions was comparable among all modern preparations affecting <1% of patients. Hence, intravenous iron therapy is reserved for iron deficiency anemia patients with intolerance or unresponsiveness of oral iron. As per European drug label, intravenous iron may also be preferred when rapid correction of the iron deficit is required. In patients with inflammation, iron-deficiency should also be suspected as anemia cause when transferrin saturation is low because serum ferritin can be spuriously normal. The main treatment target for i.v. iron is an improvement of the quality of life, for which hemoglobin is a surrogate marker. An emerging complication affecting 50-74% of patients treated with ferric carboxymaltose in prospective clinical trials is hypophosphatemia - or more accurately the 6H syndrome (hyperphosphaturic hypophosphatemia triggered by high fibroblast growth factor 23 that causes hypovitaminosis D, hypocalcemia and secondary hyperparathyroidism). These biochemical changes can cause severe and potentially irreversible clinical complications, such a bone pain, osteomalacia and fractures. Individual selection of the appropriate iron therapy and evaluation of treatment response are mandatory to safely deliver improved outcome through intravenous iron therapies.