Iron Deficiency Anemia: Safety and Cost-Effectiveness of Treatment with Various Intravenous Iron Preparations
Authors: Driscoll Michael F , Forster Derek , Dyer Brandi , Laber Damian A. 
Published: April 2020

Abstract
Introduction: Iron deficiency anemia is one of the most commonly encountered hematologic medical conditions in general practice. Oral replacement of iron can be a slow and suboptimal process, limited by low absorption rates and disease-enhanced malabsorption. When clinicians are faced with patients with large iron deficits, intravenous (IV) iron is the best option. Currently there are four IV preparations available; iron sucrose, iron gluconate, low-molecular weight iron dextran and high-molecular weight iron dextran. Upon informal questioning, we found reluctancy by many physicians to use iron dextran due to fear of allergic reactions. We examine these four preparations for clinical utility, adverse drug events (ADEs), and cost-effectiveness.
Methods: We performed a systematic review and retrospective meta-analysis of studies investigating various forms of intravenous iron preparations for toxicity, ADEs, and costs. Also, we obtained actual costs of infusing intravenous iron at four hospitals in metro Louisville, KY.
Results: Fourteen studies met the criteria and were reviewed. One study compared all four iron preparations, two compared three preparations and the rest compared two. Eight had a small sample size. The number of ADEs were quite small. Data from FDAderived ADE reporting of the four IV iron preparations from 2001–2003 showed a total of 1141 per 30,063,800 doses administered, yielding an ADE rate of approximately 38 per million. Absolute rate of all ADEs for iron sucrose, iron gluconate, low molecular weight iron dextran and high molecular weight iron dextran were 19.2, 18.5, 36.9, and 117.8 per million, respectively. Absolute rates of life-threatening ADEs were significantly lower at 0.6, 0.9, 3.3, and 11.3 per million respectively for iron sucrose, iron gluconate, low molecular weight iron dextran, and high molecular weight iron dextran. Based on cost differences between iron sucrose and dextran preparations, the cost to prevent one lifethreatening ADE related to the use of lower molecular weigh iron dextran was estimated to be $5.0–7.8 million. Also the cost to prevent one low-molecular weight iron dextran related death was estimated to be $33 million. These calculations are based on cost of preparations only. Estimates based on hospital-related costs incurred due to multiple infusions vs total dose infusion (TDI) puts the estimate of cost to prevent one lower molecular weight related death over $150 million.
Conclusions: The perceived rate of ADEs related to infusion of IV iron preparations in medical practice has been overstated. Smaller studies with lower patient and total infusion numbers, and anecdotal evidence, tended to overestimate the frequency of life-threatening reactions. The incidence of ADEs and serious life-threatening ADEs, is exceedingly low for all IV iron preparations. In light of costs associated with the use of iron sucrose and iron gluconate vs iron dextran, we recommend that all clinicians re-assess the clinical utility of low molecular weight iron dextran for iron deficiency anemia necessitating parenteral iron replacement. Moreover, large doses of iron dextran can be safely given, thereby reducing costs associated with multiple small infusions of iron sucrose.