Intravenous Iron Formulations Research Articles

Ferrous iron content of intravenous iron formulations.

The observed biological differences in safety and efficacy of intravenous (IV) iron formulations are attributable to physicochemical differences. In addition to differences in carbohydrate shell, polarographic signatures due to ferric iron [Fe(III)] and ferrous iron [Fe(II)] differ among IV iron formulations. Intravenous iron contains Fe(II) and releases labile iron in the circulation. Fe(II) generates toxic free radicals and reactive oxygen species and binds to bacterial siderophores and other in vivo sequestering agents. To evaluate whether differences in Fe(II) content may account for some observed biological differences between IV iron formulations, samples from multiple lots of various IV iron formulations were dissolved in 12 M concentrated HCl to dissociate and release all iron and then diluted with water to achieve 0.1 M HCl concentration. Fe(II) was then directly measured using ferrozine reagent and ultraviolet spectroscopy at 562 nm. Total iron content was measured by adding an excess of ascorbic acid to reduce Fe(III) to Fe(II), and Fe(II) was then measured by ferrozine assay. The Fe(II) concentration as a proportion of total iron content [Fe(III) + Fe(II)] in different lots of IV iron formulations was as follows: iron gluconate, 1.4 and 1.8 %; ferumoxytol, 0.26 %; ferric carboxymaltose, 1.4 %; iron dextran, 0.8 %; and iron sucrose, 10.2, 15.5, and 11.0 % (average, 12.2 %). The average Fe(II) content in iron sucrose was, therefore, ≥7.5-fold higher than in the other IV iron formulations. Further studies are needed to investigate the relationship between Fe(II) content and increased risk of oxidative stress and infections with iron sucrose.

The role of ferric carboxymaltose in the treatment of iron deficiency anemia in patients with gastrointestinal disease.

Iron deficiency anemia (IDA) is the most common form of nutritional anemia worldwide. Iron plays a pivotal role in vital functioning of almost every organ system. IDA affects both physical and psychological functioning of humans. Oral iron is considered as first-line therapy for the treatment of IDA due to low cost, good safety profile and ease of administration. However, the absorption of oral iron is affected by several factors and incidence of gastrointestinal side effects can lead to lack of adherence to therapy as well as poor efficacy. This has led to the emergence of intravenous iron therapy which is clearly superior to oral iron with higher increment of hemoglobin levels and rapid replenishment of iron stores. Ferric carboxymaltose (FCM) is a novel non-dextran intravenous iron form which has been approved for use in patients with iron deficiency who have had inadequate response to oral iron therapy, intolerance to oral iron, or nondialysis-dependent chronic kidney disease. The safety and efficacy of using FCM for the treatment of IDA has been demonstrated in several clinical trials. One dose can provide a large amount of iron and has a very short infusion time. It should be considered as first-line therapy in patients with active inflammation like inflammatory bowel disease when gastrointestinal absorption of oral iron may be compromised. It should also be given to patients who have inadequate response to oral iron therapy. It has been shown to be noninferior to other intravenous iron formulations with a good safety profile and produced fewer anaphylactic reactions.

Efficiency of Original versus Generic Intravenous Iron Formulations in Patients on Haemodialysis.

AimsThe appropriate use of intravenous (IV) iron is essential to minimise the requirements for erythropoiesis-stimulating agents (ESAs). The clinical efficacy of generic IV iron compared to the original formulation is controversial. We evaluated the changes that were induced after switching from a generic IV iron to an original formulation in a stable, prevalent haemodialysis (HD) population.MethodsA total of 342 patients were included, and the follow-up period was 56 weeks for each formulation. Anaemia parameters and doses of ESA and IV iron were prospectively recorded before and after the switch from generic to original IV iron.ResultsTo maintain the same haemoglobin (Hb) levels after switching from the generic to the original formulation, the requirements for IV iron doses were reduced by 34.3% (from 52.8±33.9 to 34.7±31.8mg/week, p<0.001), and the ESA doses were also decreased by 12.5% (from 30.6±23.6 to 27±21μg/week, p<0.001). The erythropoietin resistance index declined from 8.4±7.7 to 7.4±6.7 IU/kg/week/g/dl after the switch from the generic to the original drug (p = 0.001). After the switch, the transferrin saturation ratio (TSAT) and serum ferritin levels rose by 6.8%(p<0.001) and 12.4%(p = 0.001), respectively. The mortality rate was similar for both periods.ConclusionsThe iron and ESA requirements are lower with the original IV iron compared to the generic drug. In addition, the uses of the original formulation results in higher ferritin and TSAT levels despite the lower dose of IV iron. Further studies are necessary to analyse the adverse effects of higher IV iron dosages.

Management of anemia in patients with inflammatory bowel disease

Anemia is one of the commonest extraintestinal manifestations of inflammatory bowel disease (IBD). The pathogenesis of anemia in IBD is complex but iron deficiency combined with inflammation is the most common factor related to the development of anemia. However, other causes such as vitamin B12 and folate deficiency, hemolysis, myelosuppression and drug also should not be overlooked. In addition to ferritin, inflammatory markers and new biochemical parameters such as hepcidin and ferritin index are being tested as diagnostic a tool. First step for treatment is disease activity control and iron supplementation. Although oral iron is widely used, intravenous iron therapy should be considered in patients who are intolerant to oral iron therapy, have severe and refractory anemia or are in active disease state. Recently, new intravenous iron formulations have been introduced and due to their safety and easy usage, they have become the standard treatment modality for managing anemia in IBD. Erythropoietin and transfusion can be considered in specific situations. Vitamin B12 and folate supplementation is also important in patients who are deficient of these micronutrients. Since anemia in IBD patients could significantly influence the disease outcome, further studies and standard guideline for IBD are needed.

Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients

Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients

Iron deficiency anemia in inflammatory bowel disease.

Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.

Evaluating plasma pharmacokinetics of intravenous iron formulations: judging books by their covers?

Intravenous (IV) iron formulations provide a clinical treatment option for patients when iron supplementation is required but oral administration is unsuitable because of intolerance or lack of efficacy. IV iron use is increasing worldwide, especially in the chronic kidney disease (CKD) population [1]. Pharmacokinetic (PK) analysis of IV iron formulations is challenging unless the compound can be directly measured or it is manufactured with a radiolabelled form of iron (e.g. Fe) to distinguish the IV iron formulation from endogenous serum iron [2]. It is also not well appreciated by clinicians that IV iron formulations exhibit zero-order or capacity-limited metabolism by the reticuloendothelial system [3]. This results in longer residence time in plasma with higher administered doses, especially with larger molecular weight formulations [3]. Commercially available IV iron formulations consist of an iron oxyhydroxide core surrounded by carbohydrate shells of various sizes and polysaccharide branch characteristics in colloidal suspensions [4]. The size of commercially available IV iron–carbohydrate complexes range from 5 to 100 nm and thus meet the definition for nanoparticles, enhancing the complexity of PK studies of these agents [4]. In this issue of Clinical Pharmacokinetics, MuellerPlock et al. [5] evaluate plasma ferumoxytol data from healthy subjects and CKD patients, using a population PK approach seeking to bridge the PK profiles between populations with iron deficiency anaemia. This is arguably one of the larger PK analyses of IV iron plasma data to date, and ferumoxytol offers the distinct advantage of being able to be directly measured by nuclear magnetic resonance. The authors show that, as previously published, ferumoxytol plasma concentration–time profiles were best fitted with a two-compartment model with nonlinear elimination, consistent with the known capacity-limited metabolism by the reticuloendothelial system [3]. A limitation of Mueller-Plock et al.’s analysis, as well as the collective published data on IV iron plasma PK, is that these data likely represent an oversimplification of the PK profile of IV iron–carbohydrate complexes. Ferumoxytol is a superparamagnetic iron oxide nanoparticle (SPION), which was originally developed for use in magnetic resonance imaging (MRI). Biodistribution data for SPIONs demonstrate that different carbohydrate shell structures determine the relative uptake by endothelial and lymphatic cells, as well as by the reticuloendothelial system [6]. Thus, analysis of only short-term plasma PK provides limited information on the ultimate disposition and fate of these agents. Ultimately, the complexity of IV iron–carbohydrate nanoparticle formulations has important implications with regard to both efficacy and safety in treatment of iron deficiency anaemia. These agents have not been well studied with regard to comparative biodistribution, metabolic fate, and potential extracellular and intracellular deposition profiles, and further evaluation of these agents is urgently needed. Analysing short-term plasma data to infer IV iron–carbohydrate PK profiles has been typically acceptable for IV iron registry trials; however, on the basis of the SPION data in the MRI literature, these agents exhibit complicated PK and pharmacodynamic (PD) profiles, which can differ vastly between agents because of carbohydrate shell heterogeneity [6]. Thus, although shortterm plasma PK profiles among groups of healthy and This comment refers to the article available at doi:10.1007/s40262-014-0203-9.

Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management.

Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff.

Iron Supplementation for Perioperative Anaemia in Patient Blood Management

In patients undergoing major surgical procedures, preoperative anaemia and perioperative allogeneic blood transfusion (ABT) have been linked to increased postoperative morbidity and mortality, as well as longer hospital stays. A multidisciplinary, multimodal, individualised strategy – collectively termed patient blood management – used to minimise or eliminate ABT is indicated to improve outcomes. This new standard of care relies on detection and treatment of perioperative anaemia (Pillar 1) and reduction of surgical blood loss and perioperative coagulopathy (Pillar 2) to harness and optimise physiological tolerance of anaemia (Pillar 3), thus allowing the use of restrictive transfusion criteria. Normalisation of preoperative hemoglobin levels is a World Heath Organization recommendation. Iron repletion should be routinely ordered when indicated. Preoperative oral iron is time-consuming and poorly tolerated with low adherence in published trials. Postoperative oral iron has been proven to be inefficacious and is no longer recommended. Preoperative and perioperative intravenous iron, with or without erythropoiesis stimulating agents, is safe and effective at reducing ABT rate and hastening the recovery from postoperative anaemia. Intravenous iron does not seem to increase the risk for postoperative thromboembolism, infection, or mortality. Newer intravenous iron formulations demonstrate potentially much lower immunogenic activity, allow complete replacement dosing in 15 to 60 minutes, markedly facilitating care, and may be cost-effective in many clinical settings.

Physicochemical and toxicological characterization of sucrose-bound polynuclear iron oxyhydroxide formulations

Intravenous iron formulations comprising of iron/iron–oxyhydroxide–carbohydrate complex are an established therapy for the treatment of iron deficiency anemia. These preparations should be subjected to exhaustive physicochemical and toxicological studies in order to establish their safety and efficacy. Following Venofer® (innovator iron–sucrose formulation), various iron sucrose similar have entered into the market with equivalent physicochemical and toxicological profile. This report describes the physicochemical and toxicological studies of a novel iron sucrose injection (IS-Claris). IS-Claris and Venofer® were subjected to various physicochemical studies such as elemental and chemical analysis; X-ray diffraction; particle size and distribution; labile iron detection, Mossbauer and Raman spectroscopy. The presence of iron oxides in IS-Claris and Venofer® could be confirmed by the major peaks at 24.65° (2θ) and 38.2° (2θ). The iron sucrose samples demonstrated similar reduction peaks of Fe(III) to Fe in their respective polarograms. The average diameter of the core of IS-Claris and Venofer® was estimated to be 2.92 ± 0.01 and 2.77 ± 0.63 nm, respectively. The Mossbauer spectra of IS-Claris and Venofer® showed a doublet with an isomer shift δ = 0.43 ± 0.01 mm/s. Moreover, the other physicochemical specifications of IS-Claris were comparable to Venofer®. The toxicological studies demonstrated that IS-Claris safety profile is equivalent to Venofer®. It could be concluded that IS-Claris could be used as a potential alternative to Venofer® with similar clinical implications.

Safety of intravenous iron formulations: facts and folklore.

It is unlikely that anyone reading this review was not taught that intravenous (IV) iron is dangerous. While early preparations were associated with an unacceptably high rate of serious adverse events, most notably anaphylactic shock, newer formulations with carbohydrate shells which bind the elemental iron more tightly, allowing for a much slower release, are very much safer with serious toxicity being marginal to absent in prospective trials. The perception of risk is fueled by misinterpretation and misinformation of the clinical nature of minor infusion reactions1, inappropriate use of premedication with diphenhydramine2 and inferences made about the relative safety of the available formulations using spontaneous adverse event reporting systems, methodologies proscribed by regulatory agencies3,4. In this article we review published evidence on the relative safety of the different formulations, highlight errors in interpretation and intervention when minor infusion reactions occur, and posit a paradigm for maximising safety with this underutilised therapeutic tool.

Long-Term Safety and Efficacy of a Novel Iron-Containing Phosphate Binder, JTT-751, in Patients Receiving Hemodialysis

ObjectiveJTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. This study investigated long-term safety and efficacy of JTT-751 for hyperphosphatemia in patients receiving hemodialysis. Design and MethodsThis was 52-week, phase 3, multicenter, open-label, dose titration, long-term study. All patients were receiving thrice-weekly hemodialysis for ≥3 months before the initiation of the study. JTT-751 was given at titrated doses between 1.5 and 6.0 g/day. Main Outcome MeasuresSafety endpoints were adverse events and adverse drug reactions. Efficacy outcomes were the change in serum phosphate, corrected serum calcium, and intact parathyroid hormone. Changes in ferritin, transferrin saturation, and doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron formulations were additional outcomes. ResultsOne hundred and eighty patients were included in the trial. Dose-titrated JTT-751 decreased mean serum phosphate after administration and satisfactorily maintained serum phosphate concentrations throughout the entire duration of the 52-week trial. Mean serum phosphate concentrations were kept lower than 5.5 mg/dL from weeks 5 to 52. The most common adverse events were gastrointestinal disorders, which were mild to moderate in intensity. Serum ferritin concentrations rose to a peak around week 28 and stabilized thereafter. The mean intravenous iron dose decreased from 57.3 mg/4 weeks (weeks 0-12) to 3.6 mg/4 weeks (weeks 28-52); weekly ESA dose declined by 25% over the same time frame, while mean hemoglobin concentrations remained stable. ConclusionJTT-751 1.5-6.0 g/day controls serum phosphorus concentrations and reduces the need for ESAs and intravenous iron in patients receiving hemodialysis.

Labile iron in cells and body fluids: physiology, pathology, and pharmacology

In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI) composition varies with metal concentration and substances with chelating groups but also with pH and the medium redox potential. Although physiologically in the lower μM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS) formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (Tf; that renders iron essentially non-labile), in systemic iron overload (IO), the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma Tf approaches iron saturation, labile plasma iron (LPI) emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of IO, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in intravenous iron formulations per se as well as in plasma (LPI) following parenteral iron administration.

Anemia in inflammatory bowel disease: A neglected issue with relevant effects

Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients.

A multicenter, randomized, active‐controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia

Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses. We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events. Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A-FCM than Group B-oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C-FCM and Group D-IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups. Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.

Physicochemical and structural characterization of iron–sucrose formulations: a comparative study

Intravenous polynuclear iron formulations are vital components in the treatment of iron deficiency anemia associated with chronic kidney disease as well as other diseases associated with gastro-intestinal and cardio-vascular system. Intravenous iron preparations consist of iron–carbohydrate nanoparticles with iron–oxyhydroxide as a core covered by carbohydrate shell. These preparations should be very well characterized in terms of their physicochemical properties and pharmacological profile in order to establish safety and efficacy. The present research work was aimed to physicochemically characterize a new generic iron–sucrose preparation (IS-Claris) and establish its equivalency with the reference product (Venofer®). Various analytical techniques including gel permeation chromatography (GPC), mass spectroscopy (MALDI-TOF), absorption spectroscopy, X-ray diffraction analysis (XRD), nuclear magnetic resonance spectroscopy (proton and 13C NMR), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were employed. It was observed that the specifications of IS-Claris obtained through these analyses reflect those of Venofer® and hence the two formulations were considered comparable.

Ferumoxytol (Rienso): new intravenous iron preparation

AbstractFerumoxytol (Rienso) is a new intravenous iron formulation for the treatment of iron‐deficiency anaemia in chronic kidney disease. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse events and Dr Matthew Brookes discusses its place in the treatment of iron‐deficiency anaemia.

OHP-078 Treatment of Postoperative Anaemia in Orthopaedic Surgery: A Budget Impact Analysis from a Hospital Perspective

BackgroundStandard postoperative anaemia management includes oral iron or intravenous iron supplementation (iron sucrose complex, ISC), erythropoietin therapy and blood transfusion. Introduction of a new intravenous iron formulation (ferric carboxymaltose, FCM),...

N001 Comparative study of two intravenous iron formulations in day-hospital: effectiveness, efficiency and security

The aim of the audit was to quantify Helpline activity: who calls and why, the amount of time spent on related activity as well as associated cost benefits and financial consequences of not having this service. Methods: A proforma was developed to capture the incoming telephone calls, this was pioloted at 4 sites with minor adjustments made prior to the audit. Each participating site recorded their Telephone Helpline activity on a promorma during February 2012. This information was entered on to a central spreadsheet for analysis. Results: There were a total of 1187 calls (72 289 per site) recorded over the 28 day period (Table 1).

Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations

ObjectivesThere is evidence of iron deficiency (ID) in patients treated with lipoprotein apheresis. Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous (i.v.) iron formulations. MethodsInclusion criteria were defined as a) serum ferritin < 300 μg/l and transferrin saturation < 20%, b) ferritin < 100 μg/l. Both iron deficient alone and ID anemic (IDA) patients were included. Other causes for anemia were ruled out by thorough history-taking and examination/blood tests. Patients were treated with six different lipoprotein apheresis methods: DALI, Liposorber D, TheraSorb LDL, HELP, MONET and Lipidfiltration. 50 patients were randomized to either ferric carboxymaltose (FCM, 500–1000 mg as single shot infusion over 20 min) or ferric gluconate (FG, 62.5 mg once weekly). Results50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency. Both i.v. iron formulations studied were equally safe (no serious adverse events (SAEs), 6 patients/group showed adverse events (AEs)) and both effective (clinically and with respect to laboratory data) in lipoprotein apheresis patients, however FCM led to a more rapid and steeper rise of iron parameters. ConclusionsID and IDA are common findings in lipoprotein apheresis patients. The pathogenesis remains yet poorly understood and is probably multifactorial. Differential diagnosis of ID/IDA is as essential as differential therapy. Handled with care, older i.v. iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients. However, novel formulations like FCM can be administered rapidly at higher doses due to high complex stability, allowing faster filling of iron stores.Newer laboratory parameters (Reticulocyte-He, low/medium/high fluorescence reticulocytes (LFR/MFR/HFR)) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy.