Anaphylaxis risk with IV iron low, but varies with formulation

Risk for anaphylaxis with intravenous (IV) iron supplementation is rare; however, the risk can vary depending on the formulation used, a new study finds.

The results of the new retrospective cohort study were published online March 29 in Annals of Internal Medicine (doi: 10.7326/M21-4009).

“The rates of anaphylaxis were very low with all IV iron products but were three- to eightfold greater for iron dextran and ferumoxytol than for iron sucrose,” wrote Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, N.J., and colleagues.

Using data from Medicare insurance claims, the researchers evaluated the incidence of anaphylaxis among patients 65 years or older receiving their first dose of one of five different IV iron formulations for the treatment of iron deficiency anemia. Patients were treated between July 2013 and December 2018 and the iron formulations were ferric carboxymaltose, ferumoxytol, ferric gluconate, iron dextran, or iron sucrose.

Overall, 167,925 patients were included and categorized based on the iron supplement they received. Dr. Dave and colleagues found that the adjusted incidence rates (IRs) for anaphylaxis per 10,000 first administrations were 9.8 cases for iron dextran (95% confidence interval [CI], 6.2 to 15.3 cases), 4.0 cases for ferumoxytol (95% CI, 2.5 to 6.6 cases), 1.5 cases for ferric gluconate (95% CI, 0.3 to 6.6 cases), 1.2 cases for iron sucrose (95% CI, 0.6 to 2.5 cases), and 0.8 cases for ferric carboxymaltose (95% CI, 0.3 to 2.6 cases).

Only those patients receiving iron dextran or ferumoxytol had anaphylactic reactions requiring hospitalization.

Using iron sucrose as the referent category, the researchers found that the odds ratios (ORs) for anaphylaxis were 8.3 for iron dextran (95% CI, 3.5-19.8) and 3.4 for ferumoxytol (95% CI, 1.4-8.3).

“Anaphylaxis is just one of many factors one should consider when deciding on the choice of IV iron therapy,” Dr. Dave noted in an interview, when asked whether he feels that these findings will change the use of parenteral iron in practice.

Acknowledging that anaphylaxis is a severe but rare complication, Dr. Dave stated that other factors such as “clinical indication, setting, dose, the number and duration of administrations required to replenish iron reserves, risk of other adverse reactions, and costs,” should also be considered when designing treatment plans using intravenous iron.

In the study, anaphylaxis was defined as reactions that occurred within 24 hours of IV iron administration and was restricted to the following:

• Anaphylaxis resulting in hospitalization.
• An outpatient or emergency department visit due to anaphylactic shock accompanied by codes relating to the administration of cardiopulmonary resuscitation or epinephrine or the occurrence of hypotension.
• Two separate encounters for anaphylactic shock within the same day representing different encounter types, that is, inpatient, outpatient, or emergency department visit.

Dr. Dave and colleagues acknowledged study limitations, such as the fact the anaphylaxis criteria included only the most severe cases and could therefore have missed milder cases of anaphylaxis secondary to IV iron. Further, they noted that these findings may not be applicable to a younger patient population.

Patients were excluded from the study if they had received IV iron between January 2007 and July 2013, had a diagnosis of HIV or end-stage renal disease, had a recent blood transfusion, or had a history of anaphylactic reactions.

The study authors disclosed no relevant financial relationships.

Risk for anaphylaxis with intravenous (IV) iron supplementation is rare; however, the risk can vary depending on the formulation used, a new study finds.

The results of the new retrospective cohort study were published online March 29 in Annals of Internal Medicine (doi: 10.7326/M21-4009).

“The rates of anaphylaxis were very low with all IV iron products but were three- to eightfold greater for iron dextran and ferumoxytol than for iron sucrose,” wrote Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, N.J., and colleagues.

Using data from Medicare insurance claims, the researchers evaluated the incidence of anaphylaxis among patients 65 years or older receiving their first dose of one of five different IV iron formulations for the treatment of iron deficiency anemia. Patients were treated between July 2013 and December 2018 and the iron formulations were ferric carboxymaltose, ferumoxytol, ferric gluconate, iron dextran, or iron sucrose.

Overall, 167,925 patients were included and categorized based on the iron supplement they received. Dr. Dave and colleagues found that the adjusted incidence rates (IRs) for anaphylaxis per 10,000 first administrations were 9.8 cases for iron dextran (95% confidence interval [CI], 6.2 to 15.3 cases), 4.0 cases for ferumoxytol (95% CI, 2.5 to 6.6 cases), 1.5 cases for ferric gluconate (95% CI, 0.3 to 6.6 cases), 1.2 cases for iron sucrose (95% CI, 0.6 to 2.5 cases), and 0.8 cases for ferric carboxymaltose (95% CI, 0.3 to 2.6 cases).

Only those patients receiving iron dextran or ferumoxytol had anaphylactic reactions requiring hospitalization.

Using iron sucrose as the referent category, the researchers found that the odds ratios (ORs) for anaphylaxis were 8.3 for iron dextran (95% CI, 3.5-19.8) and 3.4 for ferumoxytol (95% CI, 1.4-8.3).

“Anaphylaxis is just one of many factors one should consider when deciding on the choice of IV iron therapy,” Dr. Dave noted in an interview, when asked whether he feels that these findings will change the use of parenteral iron in practice.

Acknowledging that anaphylaxis is a severe but rare complication, Dr. Dave stated that other factors such as “clinical indication, setting, dose, the number and duration of administrations required to replenish iron reserves, risk of other adverse reactions, and costs,” should also be considered when designing treatment plans using intravenous iron.

In the study, anaphylaxis was defined as reactions that occurred within 24 hours of IV iron administration and was restricted to the following:

• Anaphylaxis resulting in hospitalization.
• An outpatient or emergency department visit due to anaphylactic shock accompanied by codes relating to the administration of cardiopulmonary resuscitation or epinephrine or the occurrence of hypotension.
• Two separate encounters for anaphylactic shock within the same day representing different encounter types, that is, inpatient, outpatient, or emergency department visit.

Dr. Dave and colleagues acknowledged study limitations, such as the fact the anaphylaxis criteria included only the most severe cases and could therefore have missed milder cases of anaphylaxis secondary to IV iron. Further, they noted that these findings may not be applicable to a younger patient population.

Patients were excluded from the study if they had received IV iron between January 2007 and July 2013, had a diagnosis of HIV or end-stage renal disease, had a recent blood transfusion, or had a history of anaphylactic reactions.

The study authors disclosed no relevant financial relationships.

Risk for anaphylaxis with intravenous (IV) iron supplementation is rare; however, the risk can vary depending on the formulation used, a new study finds.

The results of the new retrospective cohort study were published online March 29 in Annals of Internal Medicine (doi: 10.7326/M21-4009).

“The rates of anaphylaxis were very low with all IV iron products but were three- to eightfold greater for iron dextran and ferumoxytol than for iron sucrose,” wrote Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, N.J., and colleagues.

Using data from Medicare insurance claims, the researchers evaluated the incidence of anaphylaxis among patients 65 years or older receiving their first dose of one of five different IV iron formulations for the treatment of iron deficiency anemia. Patients were treated between July 2013 and December 2018 and the iron formulations were ferric carboxymaltose, ferumoxytol, ferric gluconate, iron dextran, or iron sucrose.

Overall, 167,925 patients were included and categorized based on the iron supplement they received. Dr. Dave and colleagues found that the adjusted incidence rates (IRs) for anaphylaxis per 10,000 first administrations were 9.8 cases for iron dextran (95% confidence interval [CI], 6.2 to 15.3 cases), 4.0 cases for ferumoxytol (95% CI, 2.5 to 6.6 cases), 1.5 cases for ferric gluconate (95% CI, 0.3 to 6.6 cases), 1.2 cases for iron sucrose (95% CI, 0.6 to 2.5 cases), and 0.8 cases for ferric carboxymaltose (95% CI, 0.3 to 2.6 cases).

Only those patients receiving iron dextran or ferumoxytol had anaphylactic reactions requiring hospitalization.

Using iron sucrose as the referent category, the researchers found that the odds ratios (ORs) for anaphylaxis were 8.3 for iron dextran (95% CI, 3.5-19.8) and 3.4 for ferumoxytol (95% CI, 1.4-8.3).

“Anaphylaxis is just one of many factors one should consider when deciding on the choice of IV iron therapy,” Dr. Dave noted in an interview, when asked whether he feels that these findings will change the use of parenteral iron in practice.

Acknowledging that anaphylaxis is a severe but rare complication, Dr. Dave stated that other factors such as “clinical indication, setting, dose, the number and duration of administrations required to replenish iron reserves, risk of other adverse reactions, and costs,” should also be considered when designing treatment plans using intravenous iron.

In the study, anaphylaxis was defined as reactions that occurred within 24 hours of IV iron administration and was restricted to the following:

• Anaphylaxis resulting in hospitalization.
• An outpatient or emergency department visit due to anaphylactic shock accompanied by codes relating to the administration of cardiopulmonary resuscitation or epinephrine or the occurrence of hypotension.
• Two separate encounters for anaphylactic shock within the same day representing different encounter types, that is, inpatient, outpatient, or emergency department visit.

Dr. Dave and colleagues acknowledged study limitations, such as the fact the anaphylaxis criteria included only the most severe cases and could therefore have missed milder cases of anaphylaxis secondary to IV iron. Further, they noted that these findings may not be applicable to a younger patient population.

Patients were excluded from the study if they had received IV iron between January 2007 and July 2013, had a diagnosis of HIV or end-stage renal disease, had a recent blood transfusion, or had a history of anaphylactic reactions.

The study authors disclosed no relevant financial relationships.