Yes, but it is extraordinarily rare—and almost never with modern formulations.
True, IgE- or IgG-mediated anaphylaxis was historically associated with the old high-molecular-weight iron dextran preparations (no longer marketed in the U.S.). Those reactions were due to the dextran shell, not the iron itself, and sometimes occurred even with dextran solutions that contained no iron.
With today’s formulations—low-molecular-weight iron dextran (INFeD®), ferumoxytol (Feraheme®), ferric carboxymaltose (Injectafer®), ferric derisomaltose (Monoferric®), ferric gluconate (Ferrlecit®), and iron sucrose (Venofer®)—the risk of anaphylaxis is less than 1 in 200,000 infusions, and fatalities are essentially unheard of. Most reactions that appear “allergic” are actually complement-activation–related pseudoallergies (CARPA) rather than true IgE-mediated events.
When in doubt, treat first and sort later: if a patient develops airway compromise, hypotension, or generalized urticaria, manage as anaphylaxis with epinephrine and supportive care, then review the event afterward to determine whether it was true allergy or CARPA.
Bottom line: Modern IV iron can rarely cause true anaphylaxis, but the likelihood is exceedingly low. Most apparent “allergic” reactions are non-allergic, complement-mediated events, and IV iron remains one of the safest parenteral treatments in clinical use.