Intravenous Iron: What are the Chances of Side Effects?

2-4 % of Infusions have infusion reactions; 1 in 17,000 Infusions have Serious Reactions

Levels of iron are relevant to hair growth and loss. Extremely low ferritin levels (0 to 15 ug/L) often are associated with hair loss. Levels 15-30 are sometimes associated with hair loss but not always. Ferritin levels 30 and above often have no link to hair loss at all despite our preoccupation with cut offs like 40, 60 or 70.
Low ferritin levels are often best addressed with oral iron supplementation. For 99.5 % of patients that is the strategy to take in order to raise ferritin levels.

Intravenous iron becomes an option for patients with hair loss when the following criteria are met:

1) ferritin levels just won’t budge upwards despite use of oral iron OR oral iron supplements are not being well tolerated and ferritin levels are low

AND

2) the doctor feels that low ferritin levels are likely still contributing to poor growth.

Intravenous (IV) iron therapy is more effective and faster acting than oral iron. However, concerns persist among some clinicians regarding the overall safety of certain IV iron formulations. This is due mainly to older formulations (particularly the high molecular weight iron dextran (HMWID) formulation) which carried higher risks of side effects. This form of HMWID was first made available in 1996.

A new study set out to determine how common infusion reactions were in patients receiving intravenous iron for iron deficiency.

The study was a multicenter cohort study. Iron infusions were given to 12 237 patients. Some had more than 1 infusion and so the total number of infusions was 35, 737.

77.5 % of patients in the study were female. Mean age was 51 years. 84 % of patients were white and 6 % were black.

There were 22 309 iron sucrose doses, 9067 iron dextran total doses, 3147 ferumoxytol doses, and 1214 ferric carboxymaltose doses.

Infusion Reactions Differed by Type of Iron Used

Overall, 3.9 % of infusions were associated with infusion reactions. The authors showed that infusion reactions were more common with iron sucrose and iron dextran than ferumoxytol or ferric carboxymaltose. Specifically, 4.3 % with iron sucrose, 3.8% with iron dextran, 1.8% with ferumoxytol, and 1.4% ferric carboxymaltose.

Serious Infusion Reactions

There were 2 serious reactions that required use of epinephrine. Those were both with iron dextran.

Premedication Increases the Risk of Iron Reaction

Interestingly, patients who received premedication were more likely to have infusion reactions. The incidence of adverse events among those who received premedication was 23-fold higher compared with those who did not (38.6% vs 1.7%).

The authors point out that use of first-generation of histamine receptor antagonists, such as diphenhydramine, account for a large majority of perceived mild hypersensitivity reactions to IV iron.. These agents routinely cause somnolence, flushing, hypotension, and tachycardia that mimic infusion-related reactions leading to a higher frequency of reported side effects. The authors remind use that even second-generation antihistamines have also been associated with flushing, palpitations, and dizziness.

It’s these reasons that are thought to contribute to 23-fold higher rate of infusion reaction compared with no premedication (38.6% vs 1.7%, P < .001).

Conclusion and Comment

The overall conclusion here was that IV iron administration is well tolerated although 1 in 20 infusions are expected to have some mild infusion reaction. These are not usually of any serious nature.

The authors point out to us that the routine use of premedications, particularly first-generation histamine receptor antagonists could potentially cause more harm than benefit in some patients by creating symptoms that could be perceived as a mild hypersensitivity reaction.

REFERENCE

Aratsu et al. Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions. JAMA Netw Open. 2022 Mar; 5(3): e224488.