Iron

Background

NoteWhy is intravenous (IV) iron used?

IV iron is used for the treatment of iron deficiency anemia when oral iron is effective or not tolerated.

NoteWhat IV iron formulations are available in the United States?

Formulations available in the United States include low-molecular-weight iron dextran (LWMID), ferric gluconate, iron sucrose, ferumoxytol, iron isomaltoside, and ferric carboxymaltose.

Important

High-molecular weight iron dextrans were discontinued in the United States due to having a higher rate of hypersensitivity reactions.

Table 1: Characteristics of iron formulations available in the United States

Generic name	Iron gluconate	Iron Sucrose	LMWID	Ferric carboxymaltose	Iron isomaltoside	Ferumoxytol
Brand name	Ferrlecit	Venofer	INFeD	Injectafer	Monofer	FeraHeme
Molecular weight (kD)	289-440	30-60	165	150	150	750
Labile iron (% injected dose)	3.3	3.5	2	0.6	1	0.8

Immediate Hypersensitivity Reactions

NoteWhat is the incidence of anaphylactic reactions with IV iron?

Anaphylactic reactions—when high-molecular weight dextrans are excluded—occur with an incidence of < 1 in 200,000.

Significant differences in reaction risk have not been shown among low-molecular weight iron dextran, iron sucrose, ferric gluconate, and ferric carboxymaltose.

NoteWhat is the mechanism of most IV iron immediate hypersensitivity reactions?

Most IV iron immediate hypersensitivity reactions are mediated through complement-activation related pseudoallergy (CARPA). Rarely, hypersensitivity reactions are IgE-mediated.

Minor Infusion Reactions

NoteWhat are the symptoms of minor infusion reactions to IV iron?

Symptoms of minor infusion reactions to IV iron include—flushing, chest/back tightness, myalgias—and, importantly, do not have any features of anaphylaxis.

NoteWhat is considered to be the main driver of minor infusion reactions to IV iron?

Labile, or also called “free,” iron is associated with minor infusion reactions to IV iron.

Skin Testing

NoteWhat is the utility of immediate skin testing for IV iron hypersensitivity reactions?

As most hypersensitivity reactions are non-IgE-mediated—rather via CARPA—skin testing has limited utility for evaluating IV iron hypersensitivity reactions; however, it may help detect the rare patients with IgE-mediated hypersensitivity.

Management

NoteWhat are some approaches to subsequent IV iron administration in patients with previous IV iron reactions?

Approaches for patients with history of mild to moderate IV iron reactions include: switching to an alternative IV iron formulation, slowing the infusion rate (e.g., 10% of recommended rate during the first 10 to 15 minutes), and/or pre-treatment with non-sedating, second generation antihistamines.

For patients with a history of anaphylactic reactions to IV iron, desensitization can be considered, such as ferric gluconate.

References

Gómez-Ramírez S, Shander A, Spahn DR, et al. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfusion. Published online April 10, 2019. doi:10.2450/2018.0156-18

Muñoz M, Gómez-Ramírez S, Bhandari S. The safety of available treatment options for iron-deficiency anemia. Expert Opin Drug Saf 2018; 17: 149-59.