Rapid (Sixty Minutes) Infusion of One Gram of Low Molecular Iron Dextran: Safety and Efficacy Profile.

Abstract

4054 Poster Board III-989 Introduction Many clinical situations are associated with the development of iron deficiency which can adversely affect energy level, physical activity, cardiovascular function, cognition, and immune responses. Oral iron, which is the primary treatment for iron deficiency, is limited by poor tolerability due to gastrointestinal (GI) side effects and resulting problems with compliance. In addition, in many patients it is not easily absorbed and does not replace iron stores rapidly enough to meet iron losses. Blood transfusions may be avoided in these patients with the use of intravenous (IV) iron. Whereas other forms of IV iron require multiple doses for complete replacement, LMWID may be administered as a total dose infusion, typically over a 4 to 6 hour period. LMWID (INFeD) is the preferred iron dextran due to the lower incidence of reported adverse reactions in the literature as compared to high (H) MWID, (DexFerrum). Numerous clinical studies of IV iron suggest that 1000 mg is an adequate dose for many patients. Our clinical practice routinely administers LMWID as a 1 g infusion over 1 hour without pre-medication. We summarize our experience with the safety and efficacy of this method of administration. Patients and Methods Data were collected for consecutive adult patients with iron deficiency who were treated with 1 gram of LMWID from August 2008 to May 2009. To avoid confounding variables patients who received erythropoiesis stimulating agents or chemotherapy were excluded from the analysis. Age, gender, height, weight, diagnosis, tests of iron status (serum ferritin, total iron binding capacity, serum iron, and percent transferrin saturation), hemoglobin (Hb), history of multiple drug allergies and/or iron allergies, dose of iron dextran, infusion rate, number of transfusions, and signs or reports of adverse reactions were recorded. As clinically important hypophosphatemia (serum phosphate <2mg/dL) has been reported with several IV iron preparations, we examined pre- and post-infusion phosphate levels. Results 189 consecutive iron deficient patients (84% female, 76% white, mean age = 51 years, mean weight = 85 Kg) were included in the analysis, 15.9% of whom had multiple drug allergies (≥ 2). The most common diagnoses were: menorrhagia, chronic kidney disease, angiodysplasia, pregnancy, GI bleed, and gastric bypass; 19% of patients had multiple diagnoses. A total of 224 1-gram doses were administered over a median infusion time of 63 minutes (interquartile range 60-66 min). No pre-medication was administered except for 1 dose of methylprednisolone prior to the test dose in each of 2 patients: one with a previous reaction to HMWID, and one with drug allergies. Following administration of LMWID, there was a significant increase from baseline in Hb of 1.2 g/dL (p <0.0001, 95% confidence interval [CI]: 1.0 to 1.4) with a median follow-up time of 3 weeks. A follow-up time of ≥ 4 weeks was associated with a greater increase in Hb than < 4 weeks (1.5 vs 1.0 g/dL, p=0.013). One patient required a transfusion following severe GI bleeding secondary to angiodysplasia. Nineteen patients (10.1%) experienced 33 adverse events (AEs). The AEs were considered treatment-related in12 patients (6.3%). The most common AEs were back pain (2.6%), headache (2.1%), and nausea (1.6%). AEs were mostly transient and resolved without therapy. Five (2.6%) patients were treated for minor reactions (3 patients received 125 milligrams of methylprednisolone during or immediately following the infusion, and 2 patients received acetaminophen). There were no serious AEs, and only 1 patient discontinued treatment due to an AE (hives). The only demographic factor that was independently associated with an increased likelihood of experiencing an AE was drug allergies. Patients with a history of > 2 drug allergies were 4.3 times more likely to experience any kind of AE than other patients (95% CI: 1.1 to 16.3, p=0.031). Mean change from baseline phosphate level was 0.0 mg/dL (95% CI: -0.1 to 0.2, p=0.537) at a median follow-up time of two weeks. No patient developed hypophosphatemia. Conclusions Our single center experience found IV administration of 1 gram of LMWID over 1 hour is a safe and effective treatment for patients with iron deficiency with the advantages of shorter treatment period, assured compliance, and a lower incidence of side effects than oral iron. Future prospective, randomized studies will help confirm these findings. Disclosures: Off Label Use: The total dose infusion of low molecular weight iron dextran, although widely used, is an off label method of administration of intravenous iron. Pappadakis:Watson Laboratories: Employment. Dahl:Watson Laboratories: Employment.

A multicenter study evaluating the effectiveness and safety of single‐dose low molecular weight iron dextran vs single‐dose ferumoxytol for the treatment of iron deficiency

“…In a study by Auerbach et al, it was found that an increased response was found in patients with follow-up evaluation 4 or more weeks following IV iron supplementation compared to those prior to 4 weeks. 11 .1%, respectively). As baseline iron labs were similar, the degree or severity of iron deficiency does not likely contribute to this difference.…”

“…Prior studies which evaluated single-dose LMWID or ferumoxytol separately reported average changes in hemoglobin of 1.2-1.9 g/dL. 7,11,12 Notably, our study utilized medians for reporting and analysis in the setting of heterogeneous data.…”

“…for LMWID and ferumoxytol, respectively. 11,12 Minor infusion reactions are thought to be due to labile/free iron or secondary to infusion rate. 4,13,14 This study found comparable rates of mild to moderate AEs between LMWID (2.3%) and ferumoxytol (2.8%) (…”

“…A timeframe of 8 to 12 weeks for post-infusion assessment was selected based on prior studies of single-dose LMWID or ferumoxytol that used follow-up labs of 4 to 8 weeks (one study allowed up to 6 months) after IV iron infusions, although greater increments were observed with follow-up greater than 4 weeks. 7,10,11 To be included in the efficacy analysis patients were required to have Figure S1. All 906 were included in the safety analysis.…”

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“…Despite study shortcomings and lack of definitive randomized trials, the iron sucrose Venofer and the iron gluconate Ferrlecit are believed to have lower risks of serious anaphylactic‐type reactions than the iron dextrans [20–27] possibly because they do not initiate an anti‐dextran response [25]. A stated advantage of iron dextran, besides lower cost, is the ability to infuse a patient's total iron requirement in one administration (total dose infusion) [28–30] so clinicians can conveniently treat patients in a single hospital or clinic visit. However, the total dose infusion of iron dextran, although widely used, is an off‐label method of administration [30] and it is not known if studies with adequately large sample sizes have been done to determine its relative safety.…”