Intravenous ferric derisomaltose for the treatment of iron deficiency anemia

Abstract

Intravenous (IV) iron is the therapy of choice when oral iron is ineffective or poorly tolerated, yet use has been limited by fears of hypersensitivity reactions (HSRs). Newer formulations that bind iron more tightly and release it more slowly have made the risk of serious or severe HSRs very low. One such formulation, ferric derisomaltose, has been approved in the United States for delivery of 1000 mg iron in a single IV infusion. Ferric derisomaltose rapidly repletes iron parameters with low rates of serious or severe HSRs. Single-infusion iron repletion offers convenience, eliminates adherence concerns, and reduces healthcare resource utilization.

FIGURE 1

Comparative labile iron pools of parenteral iron products. Labile iron adjusted with the surface/volume ratio of parenteral iron products. The surface to volume ratio is inversely proportional to the iron content. Master data for the figure are published. ⁹ Reprinted from Journal of pharmaceutical and biomedical analysis, 86, Fütterer S, Andrusenko I, Kolb U, Hofmeister W, Langguth P, Structural characterization of iron oxide/hydroxide nanoparticles in nine different parenteral drugs for the treatment of iron deficiency anaemia by electron diffraction (ED) and X‐ray powder diffraction (XRPD), 2013, with permission from Elsevier [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Patient with minor infusion reaction. (A) A typical minor infusion reaction to IV iron with flushing and chest pressure without hypotension, wheezing, stridor or periorbital edema, in 3rd trimester gravida. (B) Photograph taken the next day shows complete resolution of minor reaction, which occurred within 5 min of onset. Premedication with methylprednisolone and famotidine was administered followed by re‐challenge and successful administration of planned dose [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Comparative labile iron pools of parenteral iron products. (A) FGF23 is a circulating hormone that is synthesized primarily in osteocytes and osteoblasts, and is inactivated by cleavage. Under physiologic circumstances and following iron repletion, synthesis and cleavage are coupled to maintain circulating level within a set range. With iron deficiency, FGF23 gene transcription is increased, but additional synthesis of FGF23 is offset by increased cleavage to maintain normal circulating levels of active FGF23. (B) FCM appears to uncouple the balance between synthesis and inactivation, resulting in increased circulating intact FGF23. The mechanism is unknown, but proposed mechanisms include inhibition of cleavage in osteocytes or activation of FGF23 production in sites without the FGF23 cleavage apparatus. High circulating FGF23 directly inhibits phosphate reabsorption in the proximal tubules of the kidney, and reduces production of serum 1,25‐dihydroxyvitamin D, which in turn reduces dietary phosphate and calcium absorption. Decreased serum calcium increases PTH production to maintain serum calcium homeostasis; PTH also inhibits phosphate reabsorption. The net result is increased phosphate excretion by the kidney and potential for hypophosphatemia. FCM, ferric carboxymaltose; FGF23, fibroblast growth factor‐23; PTH, parathyroid hormone [Color figure can be viewed at wileyonlinelibrary.com]