Abstract
Introduction: Intravenous (IV) iron is an important treatment for clinicians to properly treat iron deficiency anemia (IDA). In this context, there is a concern that giving a bolus of IV iron can induce oxidative stress. Oxidative stress depends on the stability of the IV iron complex administered. As transferrin saturation (TSAT) is low in anemic patients, transferrin has the ability to trap labile iron present in the preparations and would minimize oxidative stress. In this study, we evaluated a panel of oxidative stress markers for changes to serum components (lipids and proteins) in three IV iron products, ferric carboxymaltose (FCM), iron sucrose (IS), and high molecular weight iron dextran (HMWID).
Methods: This was an open-label, multicenter, randomized study that compared the oxidative stress induced by three IV iron preparations. Female subjects with IDA as defined as hemoglobin ≤ 10 g/dL or ≤ 12 g/dL with symptoms and ferritin ≤ 100 ng/mL or ≤ 300 ng/mL with a TSAT of ≤ 30% were included. Subjects were randomized to either Group A (FCM) or Group B (IS or HMWID). The study was performed with two cohorts within each group. Cohort 1 was administered a dose of 500 mg of undiluted FCM solution at a rate of 100 mg/minute and a dose of 500 mg as IS diluted in 250 ml of 0.9% NaCl infused over 4 hours. Cohort 2 was administered a dose of 750 mg as undiluted FCM at a rate of 100 mg/minute and a dose 725 mg as HMWID diluted in 250 ml of 0.9% NaCl infused over 3 hours, with a 25 mg test dose having been administered over 5 minutes prior to the infusion. If no reactions to the 25 mg test dose were observed during a 60 minute observational period subjects went on to receive the remaining 725 mg dose of HMWID. Blood was collected at 6 different time points; screening, baseline (prior to injection), and at 2 hours, 1 day, 7 days, and 30 days post administration. Degree of oxidative stress on proteins was measured by the presence of carbonyl group and the presence of 8-isoprostane for evidence of lipid peroxidation.
Results: The safety population (all patients receiving a dose of study drug) was composed of 49 females with a mean age of 32 years, around half of them being African Americans. In the evaluable population (those in the safety group that did not have an intervention and had completed their 24 hour and Day 30 visit, did not have an infection that require IV antibiotics or antivirals after Day 0 ), a total of 22 patients were evaluated in Group A and 21 in Group B. None of the three formulations were associated with significant increases in oxidative modification to proteins or increases in lipid peroxidation. There were more variations apparent in the IS group at 30 days than in the FCM or HMWID groups for oxidative stress in proteins. In regards to lipid peroxidation, the IS group had a large range above the median compared to the other groups at 1 day post-injection, but did not differ significantly from baseline. At all time periods, the range of FCM did not vary as much as the other two formulations.
Conclusion: These data indicate no considerable increase in the proteins modified by oxidation (carbonyl group) nor do they indicate evidence of lipid peroxidation (presence of 8-isoprostane). Post-administration oxidative stress was found not to be a significant clinical concern for the IV iron formulations in this study.
Disclosures
Connor: Luitpold Pharmaceuticals: Consultancy, Honoraria, Research Funding. Butcher:Luitpold Pharmaceuticals: Employment. Off Label Use: The dose of the study drugs are different from the package insert that is approved by the FDA.
Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal
