The available intravenous iron formulations: History, efficacy, and toxicology

Abstract

A number of intravenous iron formulations have been developed over the past 65 years which rely on dextran or other compounds to prevent uncontrolled release of free iron to the circulation. High molecular weight dextran was associated with a number of serious adverse reactions and was removed from markets worldwide in 2009. The preponderance of published evidence suggests that the formulations of parenteral iron currently available in the United States, including low molecular weight iron dextran, are all safe and effective and there are no major, clinically important differences among them in terms of either efficacy or safety. For patients with chemotherapy induced anemia or with anemia of end stage renal disease who are being treated with hemodialysis, it is reasonable to use any of the iron formulations, including iron sucrose and ferric gluconate, as frequent patient encounters with health caregivers are a routine part of care and the need to administer multiple low doses of IV iron is not a major disadvantage. However, a single infusion of a total iron dose is as effective and safe when giving iron preparations containing low molecular weight iron dextran, ferumoxytol, iron isomaltoside, or ferric carboxymaltose. Use of a single total dose infusion results in a decreased number of intravenous infusions with a lower cumulative risk for infusion reactions or extravasations, a reduced need for multiple office visits and repeated utilization of medical staff, and increased convenience for physicians and patients.

Evaluation of the Reported Rates of Severe Hypersensitivity Reactions Associated with Ferric Carboxymaltose and Iron (III) Isomaltoside 1000 in Europe Based on Data from EudraVigilance and VigiBase™ between 2014 and 2017

“…As intravenous dextran was known to cause severe anaphylaxis, new intravenous iron preparations were developed consisting of dextran-free carbohydrate shells [36, 37]. Although newer intravenous iron formulations such as ferric carboxymaltose and iron (III) isomaltoside 1000 are considered to be much safer than earlier generations of iron products [14], it may be that the molecular structure, carbohydrate complexes of i.v. iron-containing products as well as the dextran heritage of iron (III) isomaltoside 1000 [38] impacts immunogenicity, resulting in differing occurrences of hypersensitivity reactions.…”

“…iron is generally considered safe, iron infusions can cause hypersensitivity reactions (HSRs) [11, 12]. As these reactions may range from mild to fatal, HSRs are of great clinical concern, especially anaphylaxis [13, 14]. Anaphylaxis is the umbrella term for an acute reaction defined as follows: a severe, life-threatening generalized or systemic hypersensitivity reaction.…”

Importance of Initial Complete Parenteral Iron Repletion on Hemoglobin Level Normalization and Health Care Resource Utilization: A Retrospective Analysis

“…Poor GI absorption due to underlying comorbidities such as inflammatory bowel disease, chronic inflammation, and malignancy also limits the effectiveness of oral iron. In patients with CKD, patients receiving hemodialysis, and patients with cancer receiving erythropoiesis‐stimulating agents (ESAs), parenteral iron therapy is often necessary because adequate iron stores are essential to achieve maximum clinical benefit from ESAs …”

“…Several parenteral iron therapies are currently available, and they vary in dose strengths and administration schedules . Iron dextran (INFeD; Allergan, Inc., Ferentino, Italy) requires a test dose due to the risk of anaphylactoid reactions.…”

Cytosolic Uptake of Large Monofunctionalized Dextrans

“…These chemical shifts were in close agreement with values reported previously. 6 Peaks in the 1 H-NMR spectra of dextrans D1 – D4 that corresponded to these shifts were integrated, and the branching of the dextrans was calculated from the values of these integrals.…”