Intravenous iron therapy is superior to oral iron or no iron in achieving sustain hemoglobin response, and the need is reduced for pack red cell blood transfusions and improve quality-of-life in multiple clinical conditions such as chronic heart failure, chronic kidney disease, inflammatory bowel disease, hemodialysis, cancer related anemia, and pregnancy
There are several intravenous iron formulations.
Six IV iron formulations are available: low weight molecular iron dextran, ferric gluconate, iron sucrose, Ferumoxytol, ferric carboxymaltose, and ferric derosomaltase.
Multiple studies show no difference in efficacy among these formulations.
IV iron typically does not cause G.I. adverse effects.
Two are iron dextrans: a high (Dexferrin) and a low molecular weight formulation (INFeD).
Low molecular weight iron dextran is better tolerated than the higher molecular weight iron dextran.
Low molecular weight, iron dextran ,Ferumoxytol, ferric carboxymaltose and ferric derosomaltase can be administered in a single infusion over 15 to 60 minutes.
Iron sucrose and gluconate require multiple IV infusions over several weeks.
The most common adverse effects of intravenous iron are mild infusion reactions such as nausea, vomiting, pruritus, headache, flushing, myalgia, arthralgia, and back or chest pain, which typically resolve within 48 hours.
Severe hypersensitivity reactions, including anaphylaxis, are rare but can be life-threatening, with risk varying by formulation and highest for older iron dextran preparations.
Mild hypersensitivity reactions may present as flushing, urticaria, pruritus, or chest/back pressure.
Severe reactions (anaphylaxis, profound hypotension, dyspnea) occur in less than 1% of cases: highest rates seen in iron dextran and ferumoxytol, and lowest in ferric carboxymaltose and ferric derisomaltose.
Most reactions are non-IgE mediated and related to complement activation.
Hypophosphatemia is a notable adverse effect, especially with ferric carboxymaltose, and can lead to osteomalacia and fractures with repeated dosing.
Other rare adverse effects include transient increases in liver enzymes, hyperferritinemia, thrombocytopenia, and injection site reactions such as pain or skin staining from extravasation.
To minimize risk include slowing infusion rates, and administration in settings equipped for emergency management.
Premedication and test doses are generally not required for modern formulations.
The most serious adverse reaction to IV iron is anaphylaxis.
Anaphylaxis is rare but is much more common with high molecular weight iron dextran than with other preparations.
The incidence of life-threatening adversity events with iron dextran is about 0.035%, and the overall rate of adverse reactions is 0.5% per year (Walters BA et al).
Concerns exist it that intravenous iron may promote endothelial damage and promote atherosclerosis by generating oxidative stress, and that intravenous iron might decrease chemotaxis, phagocytosis and intracellular killing ability of white blood cells and limit the ability to control infections.
Two salts exist-ferric gluconate (Ferrlicit, Nulecit) and iron sucrose (Venofer).
Iron sucrose ferumoxytol (Feraheme).
Ferumoxytol (Feraheme) can be adminstered very rapidly, and is used for anemia of chronic renal failure.
Intravenous iron replacement therapy is an option for patients with absolute iron deficiency or functional iron deficiency i.e. iron-restricted erythropoiesis.
Intravenous iron replacement therapy should be considered for individuals with serum ferritin levels below 100 ng per mL with transferrin saturation levels below 50%, and who are not responsive to erythropoiesis stimulating agents.
When intravenous iron is administered in combination with erythropoiesis stimulating agents in patients with end-stage kidney disease, their hemoglobin levels are increased compared to those patients who receive erythropoiesis stimulating agents alone, and required erythropoiesis stimulating agents dose to maintain hemoglobin levels is decreased.
Intravenous iron replacement therapy is less expensive, safer and more physiologic than transfusion therapy for anemia.
Adverse events range from 5.2 events per million 100 mg dose equivalents for iron sucrose to 746 events for 100 mg dose equivalents for ferumoxytol (Bailie GR et al).
The risk of adverse events is higher for ferumoxytol compared to iron sucrose and f2242ic gluconate.
The risk of death is 475 times higher with ferumoxytol compared to iron sucrose and f2242ic gluconate.
Iron dextran has higher risk of death, and higher risks of serious adverse events compared to iron sucrose, and higher risk of death of the major events compared to ferric gluconate.
Iron sucrose and iron gluconate have much smaller risk of all adverse events, deaths, serious adverse events than ferumoxytol and to a lesser extent iron dextran.
Iron dextran is associated with the higher risk of allergic reactions compared to sucrose or gluconate.
No data show that the use of pre-medications for these formulations are beneficial.
IV iron serious adverse reactions incidence of less than 1 in 200,000 when high- molecular iron dextran is avoided.
With first exposure to intravenous iron preparations the risk of anaphylaxis is highest for iron dextran and lowest for iron sucrose.
Anaphylaxis occurs in approximately one of every 200,000 IV iron infusions with no significant differences among formulations.
Minor infusion reactions of facial flushing, chest pressure, and back tightness can occur with IV iron, and these reactions are not associated with wheezing, strider, periorbital edema or hemodynamic compromise.
Infusion reactions are believed to be complement mediated, and resolve with stopping the infusion.
The infusion can be restarted at a slower rate, and other medications are not required.
With respect to other available intravenous iron preparations; a higher rate of reactions to high-molecular-weight iron dextran compared with low-molecular-weight iron dextran, sodium ferric gluconate, and iron sucrose.
Sodium ferric gluconate and iron sucrose had the lowest rate of adverse drug reactions and life-threatening events.
The incidence of major adverse drug reactions with iron sucrose and sodium ferric gluconate is about 2/100,000 100-mg doses of each drug administered; about 4/100,000 100-mg doses for low-molecular-weight iron dextran; and 12/100,000 100-mg doses for high-molecularweight iron dextran.
The incidence of life-threatening adverse drug reactions is 0.6, 0.9, 3.3, and 11.3/million 100-mg doses for iron sucrose, sodium ferric gluconate, low-molecular-weight iron dextran, and high-molecular-weight iron dextran, respectively.