ferlixit and Anemia--Iron-Deficiency

Iron deficiency is common in patients on chronic dialysis, and most require iron-replacement therapy. In addition to absolute iron deficiency, many patients have functional iron deficiency as shown by a suboptimal response to the use of erythropoietin-stimulating agents. Both absolute and functional iron-deficiency anemia have been shown to respond to intravenous (IV) iron replacement. Although parenteral iron is an efficacious method and superior to standard doses of oral iron in patients on hemodialysis, there are ongoing safety concerns about repeated exposure potentially enhancing infection risk and cardiovascular disease. Each IV iron product is composed of an iron core with a carbohydrate shell. The avidity of iron binding and the type of carbohydrate shell play roles in the safe maximal dose and the frequency and severity of acute infusion reactions. All IV iron products are taken up into the reticuloendothelial system where the shell is metabolized and the iron is stored within tissue ferritin or exported to circulating transferrin. IV iron can be given as large intermittent doses (loading therapy) or in smaller doses at frequent intervals (maintenance dosing regimen). Limited trial data and observational data suggest that a maintenance dosing regimen is more efficacious and possibly safer than loading therapy. There is no consensus regarding the preferred method of iron repletion in patients on peritoneal dialysis, although small studies comparing oral and parenteral iron regimens in these patients have shown the latter to be more efficacious. Use of IV iron in virtually all hemodialysis and many peritoneal dialysis patients remains the standard of care.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Hemoglobins; Humans; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Renal Dialysis; Transferrin

Rates of postpartum hemorrhage have been increasing in Canada over the last 10 years, with postpartum iron deficiency anemia as the most common consequence. Postpartum anemia is treated with oral iron supplementation and/or blood transfusion. Recent studies have evaluated the use of parenteral iron as a better tolerated treatment modality. Compared with oral iron supplements, parenteral iron is associated with a more rapid rise in serum ferritin and hemoglobin and improved maternal fatigue scores in the postpartum period. It may also decrease rates of blood transfusion. Parenteral iron may be considered in select clinical situations for the treatment of postpartum anemia.. Les taux d’hémorragie postpartum ont connu une hausse au Canada depuis les 10 dernières années, la manifestation d’une anémie ferriprive postpartum en étant la conséquence la plus courante. L’anémie postpartum est prise en charge au moyen d’une supplémentation orale en fer et/ou d’une transfusion sanguine. De récentes études ayant évalué l’utilisation de fer parentéral ont indiqué qu’il s’agissait d’une modalité de traitement mieux tolérée. Par comparaison avec les suppléments oraux de fer, le fer parentéral est associé à une hausse plus rapide des taux sériques de ferritine et d’hémoglobine, en plus de mener à une amélioration des scores de fatigue maternelle au cours de la période postpartum. Le fer parentéral pourrait également mener à une diminution des taux de transfusion sanguine. Son utilisation pourrait être envisagée dans certaines situations cliniques particulières, aux fins de la prise en charge de l’anémie postpartum.

Topics: Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Parenteral; Iron-Dextran Complex; Puerperal Disorders

Iron deficiency and anaemia occur in particular in women or as comorbid conditions to a varietyof chronic diseases. Besides oral preparations, parenteral iron therapies are also available for the treatment of iron deficiency or anaemia. In the light of the growing importance and increasing number of parenteral iron preparations, theirpharmacology and application as well as the chronology of their approvals and thecharacteristicsof the various preparations are presented herefor comparison.. Review.. To date, there are three different generations of parenteral iron preparations, which differ in terms of stability, safety and dosage. In particular, the active substances of the third generation, ferric carboxymaltose, iron isomaltoside and ferumoxytol are characterised by high complex stability and comparable safety, also allowing rapid application of high doses of iron.. High molecular weight iron dextran, as a representative of 1st generation iron preparations, should no longer be used if possible, as more recent i.v. iron preparations are available with considerably lower risk of serious anaphylactic reactions. Ferrous gluconate and iron sucrose, as representatives of the 2nd generation, are very efficient preparations, but they require frequent visits to the clinic or the doctor, as they may only be administered in low doses because of labile iron complexes. The three 3rd generation parenteral iron formulations have advantages in handling in everyday practice, since they offer comparably good safety profiles, high complex stability and thus the possibility of rapid application of high doses of iron up to the total cumulative dose. Furthermore, test doses are not required with these preparations, which also simplifies their use.

Topics: Anemia, Iron-Deficiency; Disaccharides; Dose-Response Relationship, Drug; Drug Substitution; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Maltose; Structure-Activity Relationship; Treatment Outcome

Iron deficiency often occurs in patients with chronic kidney disease and can be effectively treated with parenteral supplementation of iron. In these patients, prompt application of iron therapy can help to reduce the dependence of erythropoietin-stimulating agents and effectively treat anemia. Correct evaluation of iron metabolism in CKD patients can be difficult. Duration of and response to therapy should always be considered while planning parenteral supplementation of iron. The main safety aspects of parenteral iron preparations relate to their possible anaphylactic potential and the potential induction of oxidative stress due to the release of free iron. However, parenteral iron supplementation is usually safe and without major side effects. Regarding current data, none of the iron preparations is showing definitive superiority. Although uncommon, iron preparations containing dextran can lead to severe side effects, therefore these preparations appear to have an inferior safety profile. Due to limited data, a comparison of third-generation iron preparations with previous preparations is not possible. Recently, for the first time, the third generation iron preparation ferumoxytol has been directly compared to iron sucrose. From this data and others, it remains unclear whether third generation iron preparations show safety-relevant superiority.

Topics: Administration, Oral; Anaphylaxis; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Humans; Infusions, Intravenous; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Oxidative Stress; Renal Dialysis

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Erythropoiesis; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Injections, Intravenous

Despite the proven benefits of intravenous (i.v.) iron therapy in anemia management, it remains underutilized in the hemodialysis population. Although overall i.v. iron usage continues to increase slowly, monthly usage statistics compiled by the US Renal Data System suggest that clinicians are not implementing continued dosing regimens following repletion of iron stores. Continued therapy with i.v. iron represents a key opportunity to improve patient outcomes and increase the efficiency of anemia treatment. Regular administration of low doses of i.v. iron prevents the recurrence of iron deficiency, enhances response to recombinant human erythropoietin therapy, minimizes fluctuation of hemoglobin levels, hematocrit levels, and iron stores, and may reduce overall costs of care. This article reviews the importance of i.v. iron dosing on a regular basis in the hemodialysis patient with iron-deficiency anemia and explores reasons why some clinicians may still be reluctant to employ these protocols in the hemodialysis setting.

Topics: Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Drug Resistance; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Inflammation; Injections, Intravenous; Iron; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis; Risk Assessment; Treatment Outcome

Intravenous iron is widely used to maintain adequate iron stores and prevent iron deficiency anemia in patients with chronic kidney disease, yet concerns remain about its long-term safety with respect to oxidative stress, kidney injury, and accelerated atherosclerosis, which are the subjects of this review. Three parenteral iron formulations are available for use in the United States: Iron dextran, iron gluconate, and iron sucrose. Iron dextran, especially the high molecular form, has been linked with anaphylactoid and anaphylactic reactions, and its use has been declining. A portion of intravenous iron preparations is redox-active, labile iron available for direct donation to transferrin. In vitro tests show that commonly available intravenous iron formulations have differing capacities to saturate transferrin directly: Iron gluconate > iron sucrose > iron dextran. Intravenous iron treatment produces oxidative stress, as demonstrated by increases in plasma levels of lipid peroxidation products (malondialdehyde), at a point that is much earlier than the time to peak concentration of catalytically active iron, suggesting a direct effect of iron sucrose on oxidative stress. Furthermore, iron sucrose infusion produces endothelial dysfunction that seems to peak earlier than the serum level of free iron. Intravenous iron sucrose infusion also has been shown to produce acute renal injury and inflammation as demonstrated by increased urinary albumin, enzyme (N-acetyl-beta-glucosaminidase), and cytokine (chemokine monocyte chemoattractant protein-1) excretions. Although the long-term dangers of intravenous iron are unproved, these data call for examination of effects of intravenous iron on the potential for long-term harm in patients with chronic kidney disease.

Topics: Acute Kidney Injury; Anemia, Iron-Deficiency; Animals; Atherosclerosis; Endothelium, Vascular; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Inflammation; Infusions, Intravenous; Iron-Dextran Complex; Oxidative Stress; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors; Transferrin

Ferric iron (Fe)-carbohydrate complexes are widely used for treating Fe deficiency in patients who are unable to meet their Fe requirements with oral supplements. Intravenous Fe generally is well tolerated and effective in correcting Fe-deficient states. However, the complexing of Fe to carbohydrate polymers does not block its potent pro-oxidant effects; systemic free radical generation and, possibly, tissue damage may result. The purpose of this review is to (1) underscore the capacity of currently used parenteral Fe formulations to induce oxidative stress, (2) compare the severity of these oxidant reactions with those that result from unshielded Fe salts and with each other, and (3) speculate as to the potential of these agents to induce acute renal cell injury and augment systemic inflammatory responses. The experimental data that are reviewed should not be extrapolated to the clinical setting or be used for clinical decision making. Rather, it is hoped that the information provided herein may have utility for clinical hypothesis generation and, hence, future clinical studies. By so doing, a better understanding of Fe's potential protean effects on patients with renal disease may result.

Topics: Acute Kidney Injury; Adenosine Triphosphate; Anemia, Iron-Deficiency; Animals; Endothelial Cells; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Inflammation; Infusions, Intravenous; Iron Compounds; Iron-Dextran Complex; Kidney Cortex; Kidney Tubules, Proximal; Lipid Peroxidation; Mitochondria; Oxidative Stress; Renal Dialysis; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Parenteral iron therapy is occasionally necessary for patients intolerant or unresponsive to oral iron therapy, for receiving recombinant erythropoietin therapy, or for use in treating functional iron deficiency. There are now three parenteral iron products available: iron dextran, ferric gluconate, and iron sucrose. We summarize the advantages and disadvantages of each product, including risk of anaphylaxis and hypersensitivity, dosage regimens, and costs. The increased availability of multiple parenteral iron preparations should decrease the need to use red cell transfusions in patients with iron-deficiency anemia.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Injections, Intravenous; Iron-Dextran Complex

Absolute or functional iron deficiency is a common problem in chronic disease which may lead to iron-deficient erythropoesis. Moreover, lack of available iron is the most common reason for unresponsiveness to epoetin in patients on chronic dialysis. Measurements of serum ferritin, transferrin saturation and percentage of hypochromic red blood cells allow the assessment of iron status. Lack of iron resorption and dose-dependent side-effects limit oral supplementation in a number of patients. Several iron preparations are available for intravenous substitution, especially the newly registered iron-saccharose offers safe and reliable iron supplementation and reduces the risk of anaphylaxis and iron toxicity. This review discusses new guidelines concerning diagnosis of iron status, indication for therapy and application of intravenous iron preparation.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Child; Erythrocyte Count; Erythropoiesis; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Infusions, Intravenous; Injections, Intravenous; Iron Deficiencies; Male; Renal Dialysis; Sucrose; Time Factors; Transferrin

Anemia associated with end stage renal disease can diminish quality of life substantially. Maintaining a stable hematocrit and stable hemoglobin levels affords many advantages. Improvement of anemia management is possible with the implementation of continuous quality improvement (CQI). Our review of the literature motivated us to switch from iron dextran injection, which can induce anaphylactic reactions and has other associated problems, to sodium ferric gluconate complex injection. This enables us to safely provide iron supplementation without the precautions that were in place for iron dextran. Our methods for creating and implementing CQI in the dialysis program at our university hospital are described.

Topics: Algorithms; Anaphylaxis; Anemia, Iron-Deficiency; Decision Trees; Erythropoietin; Ferric Compounds; Ferritins; Hemoglobins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Renal Dialysis; Total Quality Management; Transferrin

Intravenous iron has been found to be an important adjunctive therapy in the treatment of anemia for patients on dialysis. In the United States, iron dextran had been the only form available for parenteral use until 1999. This agent has been associated with a concerning number of severe adverse reactions, in some cases resulting in patients' deaths. Recently, a form of iron used for many years in Europe, sodium ferric gluconate complex in sucrose, was approved for intravenous use in the United STATES: Because this agent does not contain the immunogenic dextran component of iron dextran, it is expected that the safety profile of this drug should be superior to that of iron dextran. The purpose of this review is to critically appraise the relevant literature and to synthesize the information into a strategy for clinical use of this drug.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Humans; Infusions, Intravenous; Injections, Intravenous; Iron; Iron-Dextran Complex; Recombinant Proteins; Renal Dialysis; Transferrin

In the symposium "Anemia Management: Recognizing Opportunities and Improving Outcomes Through Nursing Interventions," Gail Wick discussed the nephrology nurse as a clinical change agent in the management of anemia of chronic renal failure. Matthew Lewis discussed the profile of sodium ferric gluconate complex, a new parenteral iron product, and Jamie Foret described his clinic's experience and research with this product. These discussions highlight how nurses, using effective and safe tools such as sodium ferric gluconate complex, can improve outcomes for hemodialysis patients.

Topics: Anemia, Iron-Deficiency; Drug Monitoring; Ferric Compounds; Ferritins; Health Services Needs and Demand; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Leadership; Nurse's Role; Nursing Assessment; Patient Care Team; Renal Dialysis; Safety; Total Quality Management; Treatment Outcome

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

Better anemia management has dramatically improved the lives of many patients with end stage renal disease (ESRD). Nephrology professionals frequently use two tools--erythropoietin and supplemental iron--to manage anemia. The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) suggests that most ESRD patients will need intravenous (i.v.) iron to optimize their response to erythropoietin. In this report, the author reviews published studies showing that i.v. iron reduces erythropoietin dose requirements, resulting in cost savings. She presents data from her center illustrating that i.v. administration of the newly approved Ferrlecit (sodium ferric gluconate) also improves anemia management and reduces erythropoietin dose requirements. The author reviews studies showing the efficacy of i.v. iron as monotherapy for anemia in ESRD patients. These data support the importance of i.v. iron as an agent to be used alone or in conjunction with erythropoietin in the management of anemia in patients with ESRD.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cost Savings; Drug Administration Schedule; Drug Costs; Drug Monitoring; Erythropoietin; Female; Ferric Compounds; Humans; Injections, Intravenous; Kidney Failure, Chronic; Renal Dialysis; Time Factors

Use of recombinant human erythropoietin in patients with end-stage renal disease has highlighted iron deficiency as the major cause of resistant anemia. The current mainstay of intravenous (i.v.) iron replacement therapy, iron dextran, has been shown in prior studies to have a risk of serious life-threatening anaphylaxis of just under 1 per 100 patients exposed. The current study assessed the safety profile of an alternative i.v. iron, sodium ferric gluconate complex in sucrose (Ferrlecit), as compared with iron dextrans. Sodium ferric gluconate complex in sucrose, a unique chemical preparation, has been in use since 1959, principally in Europe, at a rate of approximately 2.7 million i.v. doses per year (1992 to 1996) in Germany and Italy alone. For iron dextran, usage in the United States was comparable--principally renal hemodialysis--and estimated from market sources at 3.0 million doses per year (1995). From 1976 to 1996, there were 74 allergic adverse events reported for sodium ferric gluconate complex in sucrose to the World Health Organization (WHO), German Health Bureau, and the manufacturer (all combined). For the years 1992 to 1996, sodium ferric gluconate complex in sucrose had an allergy event reporting rate of 3.3 allergy episodes per million doses per year compared with a similar rate of 8.7 reported allergy events per million doses per year for iron dextran in the United States in 1995. Case fatalities for sodium ferric gluconate complex in sucrose and iron dextran within these reports were then compared. For sodium ferric gluconate complex in sucrose, there were no reports of deaths over the entire period (1976 to 1996). However, for iron dextrans, there were 31 fatalities among 196 allergy/anaphylaxis cases reported in the United States between 1976 and 1996, yielding a case-fatality rate of 15.8%. These data show that sodium ferric gluconate complex in sucrose, when compared with iron dextrans in comparably sized patient usage populations with similar total rates of reporting of allergic events, has a significantly lower reported mortality rate (P < 0.001). Thus, the data justify usage of sodium ferric gluconate complex in sucrose as the safer iron replacement therapeutic agent.

Topics: Anaphylaxis; Anemia, Iron-Deficiency; Drug Carriers; Drug Hypersensitivity; Drug Utilization; Europe; Ferric Compounds; Germany; Hematinics; Humans; Iron-Dextran Complex; Italy; Renal Dialysis; Sucrose; United States

The use of sodium ferric gluconate in sucrose injection (Ferrlecit) in the treatment of anemia in patients with end stage renal disease (ESRD) was the major topic at the symposium "Iron Management: Innovative Solutions to Persistent Challenges," held April 14, 1999 during the annual ANNA 30th National Symposium in Baltimore, Maryland. Chairperson Susan Vogel, MHA, RN, CNN, addressed the challenges of anemia management and the limitations of oral iron supplements. She described available intravenous (i.v.) iron therapies and reviewed clinical trial data that demonstrated an excellent safety and efficacy profile for the newly approved i.v. iron supplement, sodium ferric gluconate. Suzanne Schweitzer, RPh, MPH, discussed iron metabolism and the U.S. labeling for sodium ferric gluconate, with a focus on dosing and administration. In the final presentation, Suzanne Seiler, RN, described her clinic's experience with sodium ferric gluconate and provided an experimental dosing and monitoring protocol. Together, these presentations suggest that sodium ferric gluconate is an important new tool for meeting the challenges of iron management in ESRD patients.

Topics: Anemia, Iron-Deficiency; Chemistry, Pharmaceutical; Drug Monitoring; Ferric Compounds; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Renal Dialysis

The management of anemia in dialysis patients involves a comprehensive understanding of the role of erythropoietin deficiency and of the importance of adequate available iron. It is clear that iron and recombinant human erythropoietin (rHuEPO) in concert allow the clinician to achieve a given target hematocrit in dialysis patients. By first repleting and then maintaining iron stores, and with an appreciation of the concept of functional iron deficiency, the nephrologist can achieve target hematocrits with the lowest necessary dose of rHuEPO. Iron repletion and maintenance is difficult to achieve with oral iron, and parenteral iron is needed in most cases. New protocols for ongoing parenteral maintenance therapy with iron dextran or iron gluconate, a form of iron likely to be available soon in the United States, should lead to achievement of target hematocrits in a greater number of patients and be cost-effective in improving patient outcomes.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Erythropoietin; Ferric Compounds; Hematinics; Hematocrit; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Iron deficiency anemia is among the most frequent causes of disability. Intravenous iron is the quickest way to correct iron deficiency, bypassing the bottleneck of iron intestinal absorption, the only true mechanism of iron balance regulation in human body. Intravenous iron administration is suggested in patients who are refractory/intolerant to oral iron sulfate. However, the intravenous way of iron administration requires several precautions; as the in-hospital administration requires a resuscitation service, as imposed in Europe by the European Medicine Agency, it is very expensive and negatively affects patient's perceived quality of life. A new oral iron formulation, Sucrosomial iron, bypassing the normal way of absorption, seems to be cost-effective in correcting iron deficiency anemia at doses higher than those usually effective with other oral iron formulations. In this multicentric randomized study, we analyze the cost-effectiveness of intravenous sodium ferrigluconate vs oral Sucrosomial iron in patients with iron deficiency anemia refractory/intolerant to oral iron sulfate without other interfering factors on iron absorption.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Humans; Male; Middle Aged; Prospective Studies

To assess the short-term efficacy and safety of an accelerated intravenous iron regimen in hospitalized patients with heart failure and iron deficiency.. Prospective, single-arm, open-label study.. Large tertiary care medical center.. Thirteen patients with New York Heart Association class III-IV heart failure, anemia (hemoglobin level ≤ 12.0 g/dl), and iron deficiency (ferritin level < 100 ng/ml, or ferritin level of 100-300 ng/ml with transferrin saturation < 20%) hospitalized between April 2011 and December 2013.. All patients received sodium ferric gluconate 250 mg in 100 ml of normal saline intravenously over 2 hours twice/day until the iron deficit was corrected or the patient was discharged.. Changes in hematologic parameters were assessed at 1-4 weeks after therapy. Patients received a mean ± standard deviation (SD) total iron dose of 1269 ± 207 mg over 3.4 ± 1.0 days. After a mean ± SD follow-up of 13.1 ± 5.6 days, intravenous iron increased hemoglobin level by 1.2 g/dl (95% confidence interval [CI] 0.45-1.9, p=0.005), ferritin level by 364.2 ng/ml (95% CI 129.7-598.7, p=0.007), and transferrin saturation by 10.5% (95% CI 6.5-14.6%, p<0.001). Changes in hemoglobin level did not correlate with volume status, as determined by differences in body weight. No significant changes in blood pressure or heart rate were observed. Adverse events were few and minor in severity (e.g., nausea, constipation, and abdominal discomfort).. An accelerated intravenous iron regimen improved hematologic parameters and was well tolerated in hospitalized patients with advanced heart failure. A randomized multicenter trial comparing this regimen with placebo is warranted.

Topics: Anemia, Iron-Deficiency; Female; Ferric Compounds; Heart Failure; Hematinics; Hemoglobins; Hospitalization; Humans; Infusions, Intravenous; Male; Pilot Projects; Prospective Studies; Time Factors; Treatment Outcome

Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2-2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin phenotype affects iron-induced oxidative stress in CKD patients. Therefore, the present study examines the influence of carnitine treatment on the intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and whether Hp phenotype affects this response.. Current Controlled Trials ISRCTN5700858. This study included 26 anemic (Hb = 10.23 ± 0.28) CKD patients (stages 3-4) that were given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20 mg/kg, IV) prior to IVIR. Weekly blood samples were drawn before and after each IVIR for Hp phenotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses.. Eight percent of CKD patients were Hp1-1, 19 % Hp2-1, and 73 % Hp2-2. IVIR for 4 weeks did not increase hemoglobin levels, yet worsened the oxidative burden as was evident by elevated plasma levels of AOPP. The highest increase in AOPP was observed in Hp2-2 patients. Simultaneous administration of Carnitine with IVIR abolished the IVIR-induced oxidative stress as evident by preventing the elevations in AOPP and NGAL, preferentially in patients with Hp2-2 phenotype.. This study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients. Our finding, that co-administration of Carnitine with IVIR preferentially attenuates the adverse consequences of IVIR, suggests a role for Carnitine therapy in these patients.

Topics: Acute-Phase Proteins; Advanced Oxidation Protein Products; Aged; Anemia, Iron-Deficiency; C-Reactive Protein; Carnitine; Cross-Over Studies; Female; Ferric Compounds; Genotype; Haptoglobins; Humans; Lipocalin-2; Lipocalins; Male; Middle Aged; Oxidative Stress; Phenotype; Prospective Studies; Proto-Oncogene Proteins; Renal Insufficiency, Chronic

Iron deficiency anemia frequently occurs in gastrectomized patients.. Serum iron levels following the ingestion of a single oral dose of 105 mg elemental iron, taken as ferrous sulfate (FeS) or ferric gluconate (FeG), have been evaluated in 20 gastrectomized patients (and 20 controls). All subjects participated on 2 different test days, 1 month apart: they took a single dose of 105 mg elemental iron as FeS or FeG after a night of fasting. Serum iron concentrations at baseline, 30, 60, 120 and 180 min after the oral dose administration were measured.. In patients and controls receiving FeG, serum iron levels did not significantly change. After oral ingestion of FeS, patients' serum iron levels gradually increased. The increase in serum iron levels was 148 and 168% at 120 and 180 min in patients (p < 0.0001 for both evaluations), whilst in controls, it was 216% at 120 min and 234% at 180 min, i.e. significantly higher than in gastrectomized patients (p < 0.001 for both evaluations).. In gastrectomized patients, a single oral dose of FeS shows a significant increase in iron serum concentration, albeit lower than in controls. Further studies on a larger sample of patients will be necessary to confirm these results.

Topics: Absorption; Administration, Oral; Adult; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferrous Compounds; Follow-Up Studies; Gastrectomy; Humans; Iron; Male; Middle Aged; Single-Blind Method; Treatment Outcome

There 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.. Inclusion 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).. 50 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.. ID 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.

Topics: Aged; Anemia, Iron-Deficiency; Biomarkers; Blood Component Removal; Chemistry, Pharmaceutical; Drug Administration Schedule; Dyslipidemias; Female; Ferric Compounds; Ferritins; Germany; Hematinics; Humans; Infusions, Intravenous; Lipoproteins; Male; Maltose; Middle Aged; Time Factors; Transferrin; Treatment Outcome

Among patients with chronic kidney disease (CKD), differences in proteinuria are seen between intravenous iron preparations after a single dose exposure. This study examined differences in proteinuria between two intravenous iron preparations after multiple doses.. Patients with iron-deficiency anemia and CKD, stratified by angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor-blocker (ARB) use, were randomized to iron sucrose or ferric gluconate. Each patient at 12 centers received 100 mg of study drug weekly for 5 weeks. Urine protein/urine creatinine ratio was measured before each dose and frequently thereafter for 3 hours.. Postbaseline data were available from 33 patients receiving iron sucrose and 29 patients receiving ferric gluconate. Although neither preparation of intravenous iron increased the predose level of proteinuria, the proteinuric response to intravenous iron was dependent on the type of iron and ACEI/ARB use. Without ACEIs/ARBs, ferric gluconate tended to cause less proteinuria with repeated iron administration; iron sucrose did not mitigate or aggravate proteinuria. Among patients receiving ACEIs/ARBs, in contrast to ferric gluconate, which produced only mild transient proteinuria, iron sucrose produced a consistent and persistent proteinuric response that was on average 78% greater.. Although multiple doses of either intravenous iron did not increase basal levels of proteinuria, postdose proteinuria was greater with iron sucrose than with ferric gluconate. These data suggest that nephrotoxicity of iron may depend on type of intravenous iron and on ACEI/ARB use. The long-term effects on kidney function need to be further evaluated.

Topics: Adult; Aged; Albuminuria; Anemia, Iron-Deficiency; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Creatinine; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria

Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent.. In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG.. Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%.. A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Topics: Adult; Anemia, Iron-Deficiency; Drugs, Generic; Erythropoietin; Female; Ferric Compounds; Humans; Infusions, Intravenous; Male; Recombinant Proteins; Renal Dialysis; Sucrose; Sweetening Agents; Time Factors

The relative safety of parenteral iron preparations is a controversial issue in the management of anemia in chronic kidney disease (CKD), as direct head-to-head comparative trials are lacking. In this study, patients of CKD were randomized to receive intravenous low molecular weight iron dextran (ID), sodium ferrigluconate complex (SFGC), and iron sucrose (IS) at doses and infusion rates recommended by the product manufacturer. One time test dose was used only for ID and SFGC. A total of 2,980 injections (n = 339) of i.v. iron was given, and 49 patients (14.45% per patient) and a total of 56 adverse events (1.88% per infusion) were noted. Odds ratios (OR) of serious adverse drug events (ADE; i.e., death, anaphylaxis, or suspected immuno-allergic events) per patient was not significant between ID vs. SFGC (3.566) and SFGC vs. IS (2.129), whereas that between ID vs. IS (7.594) was highly significant (p = 0.034). OR of serious ADE exposure was significantly higher in ID vs. SFGC (OR = 5.670, p = 0.0147) and ID vs. IS (OR = 7.799, p < 0.001). No significant difference was seen between the three groups in terms of non-serious ADEs. Drug discontinuation occurred significantly more often with ID. One patient who developed anaphylactoid reaction with SFGC and ID tolerated iron sucrose well.

Topics: Adult; Age Factors; Analysis of Variance; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Probability; Renal Dialysis; Risk Assessment; Severity of Illness Index; Sex Factors; Treatment Outcome

Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) frequently develop anemia. Administration of recombinant human erythropoietin (rHuEPO) is effective in managing this anemia, although the additional demand for iron often results in iron deficiency. In adult patients undergoing HD, intravenous (IV) iron administration is known to replenish iron stores more effectively than oral iron administration. Nevertheless, IV iron supplementation is underutilized in pediatric patients, possibly because of unproved safety in this population. This international, multicenter study investigated the safety and efficacy of two dosing regimens (1.5 mg kg(-1) and 3.0 mg kg(-1)) of sodium ferric gluconate complex (SFGC) therapy, during eight consecutive HD sessions, in iron-deficient pediatric HD patients receiving concomitant rHuEPO therapy. Safety was evaluated in 66 patients and efficacy was evaluated in 56 patients. Significant increases from baseline were observed in both treatment groups 2 and 4 weeks after cessation of SFGC dosing for mean hemoglobin, hematocrit, transferrin saturation, serum ferritin, and reticulocyte hemoglobin content. Efficacy and safety profiles were comparable for 1.5 mg kg(-1) and 3.0 mg kg(-1) SFGC with no unexpected adverse events with either dose. Administration of SFGC was safe and efficacious in the pediatric HD population. Given the equivalent efficacy of the two doses, an initial dosing regimen of 1.5 mg kg(-1) is recommended for pediatric HD patients.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Treatment Outcome

A previous single dose placebo-controlled double-blinded trial showed an extremely low (0.4%) intolerance rate of sodium ferric gluconate complex (SFGC) in SFGC-naive haemodialysis patients. No large prospective trials have assessed the safety of SFGC during repeated exposure in the outpatient haemodialysis setting.. Chronic haemodialysis patients completing the single-dose trial of SFGC were eligible to participate in this prospective, multicentre, open-label, long-term evaluation of SFGC, designed to record adverse events occurring up to 72 h post-dose. Patients received as many as 20 ampules (1250 mg total) of SFGC at an investigator-determined dose and rate over a 9 month evaluation period.. Among 1412 enrolled patients at 54 centres, 1321 received 13,151 infusions of SFGC. Most doses (94.8%) were < or =125 mg and the majority were given over 10 min. Infusion rates ranged from <5 to 125 mg/min. There were no life-threatening events. Fifty-one patients (3.9%) experienced an adverse event, possibly related to SFGC. Of these, one experienced a serious event (hypotension). Five patients (0.4%) experienced an event that precluded SFGC readministration: pruritus (three), vasodilatation (one) and loss of taste (one). Among 372 patients (28.2%) receiving angiotensin-converting enzyme inhibitor (ACEI) therapy, adverse events were neither more common nor more severe than in the other patients.. Repeated doses of SFGC are very well tolerated in haemodialysis patients. No life-threatening events were observed in over 13,000 doses administered. Administration of SFGC to patients using ACEI is safe and does not increase the incidence or severity of adverse events to SFGC.

Topics: Aged; Anemia, Iron-Deficiency; Drug Hypersensitivity; Female; Ferric Compounds; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis

Almost all hemodialysis (HD) patients require intravenous iron therapy to correct their anemia and maintain their iron stores. Sodium ferric gluconate complex (SFGC) is approved by the Food and Drug Administration (FDA) for treatment of iron deficiency anemia in HD patients at individual doses up to 125 mg over 10 minutes (12.5 mg/min) and has been shown to have a superior safety profile compared with iron-dextran. Higher individual doses of SFGC would permit more rapid repletion of iron stores and greater flexibility in maintenance iron therapy as well as simplify treatment of peritoneal dialysis patients and chronic kidney disease patients.. The authors reviewed the safety and tolerability of higher-dose SFGC infusions (> or =250 mg) in 144 HD patients who were previously tolerant to a single 125-mg dose of SFGC. These 144 patients received a total of 590 doses of > or =250 mg of SFGC; 571 doses were 250 mg SFGC, and most of these were infused over 1 hour, an infusion rate of 4.17 mg/min. The other 19 doses were 312.5 mg (n = 1), 375 mg (n = 14), and 500 mg (n = 4). Infusion rates varied from 1.22 mg/min to 25.0 mg/min.. Only one patient was considered intolerant to higher-dosing SFGC after having pruritus after a second 250-mg dose of SFGC. Three patients had nonserious events that did not preclude further dosing of SFGC.. Administration of 250 mg SFGC over 1 hour is safe and well tolerated. Individual doses of 375 mg and 500 mg SFGC also were well tolerated, but further research and experience are needed to confirm the safety and tolerance of these doses.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Population Surveillance; Treatment Outcome

Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.. This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.. A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.. SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Cross-Over Studies; Double-Blind Method; Female; Ferric Compounds; Humans; Hypotension; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Placebos; Prospective Studies; Renal Dialysis

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.

Topics: Adult; Aged; Analysis of Variance; Anemia, Iron-Deficiency; Drug Administration Schedule; Drug Carriers; Female; Ferric Compounds; Ferritins; Hematinics; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Male; Middle Aged; Patient Selection; Renal Dialysis; Sucrose; Transferrin; Treatment Outcome; United States

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e., sodium ferric gluconate (SFG)). These products are indicated for the treatment of iron deficiency anemia and are administered intravenously. On the molecular level, iron nanomedicines are colloids composed of an iron oxide core with a carbohydrate coating. This formulation makes nanomedicines more complex than conventional small molecule drugs. As such, these products are often referred to as nonbiological complex drugs (e.g., by the nonbiological complex drugs (NBCD) working group) or complex drug products (e.g., by the FDA). Herein, we report a comprehensive study of the physiochemical properties of the iron nanoparticle product SFG. SFG is the single drug for which both an innovator (Ferrlecit) and generic product are available in the US, allowing for comparative studies to be performed. Measurements focused on the iron core of SFG included optical spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), X-ray powder diffraction (XRPD),

Topics: Anemia, Iron-Deficiency; Chemistry, Pharmaceutical; Chromatography, Gel; Drugs, Generic; Dynamic Light Scattering; Equivalence Trials as Topic; Ferric Compounds; Humans; Nanoparticles; Quality Control; Ultracentrifugation

Oral iron is recommended as first line treatment of anemia in non-dialysis chronic kidney disease (ND-CKD) patients. Sucrosomial® iron, a new generation oral iron with high absorption and bioavailability and a low incidence of side effects, has shown to be not inferior to intravenous (IV) iron in the replacement of iron deficiency anemia in patients with ND-CKD. Besides the clinical benefit, it is also important to determine the comparative total costs of oral versus IV iron administrations. The aim of this study was to perform a cost-minimization analysis of oral Sucrosomial iron, compared with IV iron gluconate from an Italian societal perspective.. Cost analysis was performed on the 99 patients with ND-CKD and iron-deficiency anemia of the randomized trial by Pisani et al. Human and material resources utilization was recorded during each iron administration. According to study perspective, direct and indirect costs were considered. Costs for each resource unit were taken from official Italian sources. Probabilistic sensitivity analyses were carried out to test the robustness of the results.. The base case analysis showed an average cost/cycle per patient of € 111 for oral iron and € 1302 for IV iron. Thus, the potential saving was equal to € 1191 per patient/cycle. The sensitivity analysis showed that the most sensitive driver is the time loss by patient and caregivers for the therapy and related-care, followed by the minutes of nursing care and the number of kilometres travelled to reach the referral centre.. This study showed that oral Sucrosomial® iron could offer specific advantages in terms of potential savings, and allowed identifying some implications for future research. Such advantages still persist with the new single dose IV iron formulation available in the market, although to a lesser extent.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Cost Savings; Costs and Cost Analysis; Drug Costs; Ferric Compounds; Health Care Costs; Hematinics; Humans; Infusions, Intravenous; Iron; Renal Insufficiency, Chronic

Iron deficiency (ID) is recognized as an important comorbidity in patients undergoing cardiac surgery; however, it still remains under-diagnosed and under-treated in clinical practice. This study aims at comparing efficacy and the effects on exercise capacity of intravenous ferric carboxymaltose (FCM) versus ferric gluconate (FG) in patients with ID anemia (IDA) resulting from cardiac surgery. We retrospectively analyzed data from our records of in-hospital patients with IDA after cardiac surgery undergoing cardiac rehabilitation. Group I was treated with FG, group II with FCM. Efficacy measures included changes (baseline vs discharge) in hemoglobin (Hb) and in distance traveled at six-minutes walking test (6MWT). Data from 74 in-patients (mean age 67.5±10.4 years, 43% women) were analyzed. At discharge, patients treated with FCM showed higher levels of Hb (11.1±1.2g/dl vs 10.2±1.1 g/dl; p=0.001), greater distance traveled at 6MWT (279.2±108.8 meters vs 236.3±72.7 meters; p=0.048), and lower in-hospital rehabilitation length of stay (20.3±7 vs 25.3±11.7 days; p=0.043) as compared to FG group. At multivariate analysis, the most powerful predictors of Hb increase >1 g/dl at discharge were transferrin levels (p=0.019) and treatment with FCM (p<0.001). FCM replacement therapy and iron serum levels were the most powerful predictors of 6MWT distance improvement (>100 meters) at discharge (p=0.13 and p=0.003, respectively). In patients with IDA following cardiac surgery, intravenous FCM is effective in restoring Hb levels and in improving exercise capacity after cardiac surgery.

Topics: Aged; Anemia, Iron-Deficiency; Cardiac Surgical Procedures; Exercise Tolerance; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Male; Maltose; Middle Aged; Retrospective Studies; Treatment Outcome

Iron deficiency is the main cause of anemia in both sexes, with women being more commonly affected. Iron therapy is currently considered an effective and safe remedy to replenish the iron storages. Iron can be administrated both orally and intravenously. In particular, intravenous (IV) iron therapy is widely used when oral iron preparations are either not tolerated or ineffective. Indeed, IV iron improves iron stores more rapidly. Two main immunological responses have been described for iron hypersensitivity reactions (HSRs): IgE-mediated allergy and complement activation-related pseudo-allergy. Here, we report 3 cases of adult patients with iron allergy, who were successfully treated with two different desensitization procedures, respectively. Analysis of these cases demonstrates that, in the presence of HSRs to iron products, desensitization is an effective and safe procedure that prevents treatment discontinuation and hence allows therapeutic target achievement.

Topics: Adult; Anemia, Iron-Deficiency; Chlorpheniramine; Dexamethasone; Female; Ferric Compounds; Hematinics; Humans; Hypersensitivity; Iron; Maltose; Middle Aged; Skin Tests

To evaluate trends in diagnosis and management of iron deficiency anemia using a large national children's hospital database in pediatric patients admitted with inflammatory bowel disease (IBD).. In this retrospective multicenter cohort study, we used the Pediatric Health Information System de-identified administrative database. Patients age <21 years with ≥2 admissions with International Classification of Disease, Ninth Revision and Tenth Revision codes for Crohn's disease or ulcerative colitis from 2012 to 2018 were included. We extracted data regarding diagnoses of anemia and/or iron deficiency, and receipt of oral iron, intravenous (IV) iron, and/or blood transfusion. Data were analyzed descriptively.. We identified 8007 unique patients meeting study criteria for a total of 28 260 admissions. The median age at admission was 15.4 years. A diagnosis of anemia was documented in 29.8% of admissions and iron studies were performed in 12.6%. IV iron was given in 6.3% of admissions and blood transfusions in 7.4%. The prevalence of the diagnosis of anemia among IBD admissions increased from 24.6% in 2012 to 32.4% in 2018 (P < .0001). There was a steady increase in the proportion of IBD admissions that used IV iron, from 3.5% in 2012 to 10.4% in 2018 (P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% (P < .0001).. Iron deficiency anemia is prevalent among pediatric patients with IBD admitted to US children's hospitals. From 2012 to 2018, there was an increase in the use of inpatient IV iron for the treatment of iron deficiency anemia and a decrease in transfusions.

Topics: Adolescent; Anemia, Iron-Deficiency; Blood Transfusion; Child; Child, Preschool; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Hematinics; Hospitalization; Humans; Infant; Iron-Dextran Complex; Male; Prevalence; Retrospective Studies; Young Adult

Anemia is a frequent complication of Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD). Intravenous (IV) iron is recommended as the initial therapy for patients with clinically active IBD, severe anemia, and intolerance to oral iron. IV iron is associated with serious adverse effects including a black box warning for anaphylaxis with iron dextran and ferumoxytol. We aimed to examine the occurrence of adverse reactions including anaphylaxis after IV iron infusions in a large database of US IBD patients.. We performed a retrospective analysis for encounters occurring between 2010 and 2014 in MarketScan, a US commercial claims database. We assessed the following adverse events: anaphylactic shock, bronchospasm, and hypotension among IBD patients receiving ferumoxytol, iron dextran, ferric gluconate, iron sucrose, and ferric carboxymaltose. We calculated the adverse event rate per 1000 infusions within 7 days of IV iron infusion.. In our study cohort of 6151 IBD patients (38.4% UC), 37 168 IV iron infusions were given (median, 3 infusions). There were very few adverse events; only 1.3% of IBD patients experienced any adverse reaction. The incident rate per 1000 infusions for any adverse event among IBD patients was highest among those receiving ferumoxytol (2.54, 95% confidence interval [CI], 1.26-5.11), ferric gluconate (1.85; 95% CI, 1.03-3.35), iron sucrose (1.74; 95% CI, 1.09-2.78), and iron dextran (0.96; 95% CI, 0.43-2.13). There were 0.24 anaphylactic shock events per 1000 IV iron infusions.. About 1.3 of 100 IBD patients ever developed any adverse event. Because adverse reactions are rare, physicians should be encouraged to adhere to recommended guidelines for iron replacement among anemic IBD patients. 10.1093/ibd/izy063_video1izy063.video15768853346001.

Topics: Administration, Intravenous; Adolescent; Adult; Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferrosoferric Oxide; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Retrospective Studies; United States; Young Adult

Despite different pharmacologic properties, little is known about the comparative safety of sodium ferric gluconate versus iron sucrose in hemodialysis patients.. Retrospective cohort study using the clinical database of a large dialysis provider (2004-2005) merged with administrative data from the US Renal Data System.. 66,207 patients with Medicare coverage who received center-based hemodialysis.. Iron formulation use assessed during repeated 1-month exposure periods (n=278,357).. All-cause mortality, infection-related hospitalizations and mortality, and cardiovascular-related hospitalizations and mortality occurring during a 3-month follow-up period.. For all outcomes, we estimated 90-day risk differences between the formulations using propensity score weighting of Kaplan-Meier functions, which controlled for a wide range of demographic, clinical, and laboratory variables. Risk differences were also estimated within various clinically important subgroups.. Ferric gluconate was administered in 11.4%; iron sucrose, in 48.9%; and no iron in 39.7% of the periods. Risks for most study outcomes did not differ between ferric gluconate and iron sucrose; however, among patients with a hemodialysis catheter, use of ferric gluconate was associated with a slightly decreased risk for both infection-related death (risk difference, -0.3%; 95% CI, -0.5% to 0.0%) and infection-related hospitalization (risk difference, -1.5%; 95% CI, -2.3% to -0.6%). Bolus dosing was associated with an increase in infection-related events among both ferric gluconate and iron sucrose users.. Residual confounding and outcome measurement error.. Overall, the 2 iron formulations studied exhibited similar safety profiles; however, ferric gluconate was associated with a slightly decreased risk for infection-related outcomes compared to iron sucrose among patients with a hemodialysis catheter. These associations should be explored further using other data or study designs.

Topics: Anemia, Iron-Deficiency; Cohort Studies; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Time Factors

Treatment of iron deficiency with intravenous (i.v.) iron is a first-line strategy to improve anaemia of chronic kidney disease. Previous in vitro experiments demonstrated that different i.v. iron preparations inhibit differentiation of haematopoietic stem cells to monocytes, but their effect on monocyte differentiation to macrophages and mature dendritic cells (mDCs) has not been assessed. We investigated substance-specific effects of iron sucrose (IS), sodium ferric gluconate (SFG), ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) on monocytic differentiation to M1/M2 macrophages and mDCs.. Via flow cytometry and microRNA (miRNA) expression analysis, we morphologically and functionally characterized monocyte differentiation to M1/M2 macrophages and mDCs after monocyte stimulation with IS, SFG, FCM and IIM (0.133, 0.266 and 0.533 mg/mL, respectively). To assess potential clinical implications, we compared monocytic phagocytosis capacity in dialysis patients who received either 500 mg IS or IIM.. Phenotypically, IS and SFG dysregulated the expression of macrophage (e.g. CD40, CD163) and mDC (e.g. CD1c, CD141) surface markers. Functionally, IS and SFG impaired macrophage phagocytosis capacity. Phenotypic and functional alterations were less pronounced with FCM, and virtually absent with IIM. In miRNA expression analysis of mDCs, IS dysregulated miRNAs such as miR-146b-5p and miR-155-5p, which are linked to Toll-like receptor and mitogen-activated protein kinase signalling pathways. In vivo, IS reduced monocytic phagocytosis capacity within 1 h after infusion, while IIM did not.. This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.

Topics: Anemia, Iron-Deficiency; Case-Control Studies; Cell Differentiation; Dendritic Cells; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Iron Compounds; Macrophages; Maltose; MicroRNAs; Monocytes; Phagocytosis

Iron deficiency (ID) and iron deficiency anemia (IDA) are common findings in patients undergoing lipoprotein apheresis (LA). Different intravenous (iv) formulations are used to treat ID in LA patients, however guidelines and data on ID/IDA management in LA patients are lacking. We therefore performed a prospective observational multi-center cohort study of ID/IDA in LA patients, comparing two approved i.v. iron formulations, ferric gluconate (FG) and ferric carboxymaltose (FCM).. Inclusion criteria were a) serum ferritin <100 μg/L or b) serum ferritin <300 μg/L and transferrin saturation <20%. Patients received either FG (62.5 mg weekly) or FCM (500 mg once in ID or up to 1000 mg if IDA was present) i.v. until iron deficiency was resolved. Efficacy and safety were determined by repeated laboratory and clinical assessment. Iron parameters pre and post apheresis were measured to better understand the pathogenesis of ID/IDA in LA patients.. 80% of LA patients treated at the three participating centers presented with ID/IDA; 129 patients were included in the study. Serum ferritin and transferrin levels were reduced following apheresis (by 18% (p < 0.0001) and by 13% (p < 0.0001) respectively). Both FG and FCM were effective and well tolerated in the treatment of ID/IDA in LA patients. FCM led to a quicker repletion of iron stores (p < 0.05), while improvement of ID/IDA symptoms was not different. Number and severity of adverse events did not differ between FG and FCM, no severe adverse events occurred.. Our results suggest that FG and FCM are equally safe, well-tolerated and effective in treating ID/IDA in LA patients. These data form the basis for follow-up randomized controlled trials to establish clinical guidelines.

Topics: Aged; Anemia, Iron-Deficiency; Biomarkers; Blood Component Removal; Drug Administration Schedule; Female; Ferric Compounds; Ferritins; Germany; Hematinics; Humans; Hyperlipoproteinemias; Infusions, Intravenous; Iron; Lipoproteins, LDL; Male; Maltose; Middle Aged; Prospective Studies; Time Factors; Transferrin; Treatment Outcome

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Thrombocytosis; Thrombophilia; Venous Thromboembolism

Oral iron replacement is the standard therapy in iron-deficiency anemia (IDA). However, 59% of patients have gastrointestinal toxicity. With impaired iron uptake from the gastrointestinal tract (in anemia of chronic disease (ACD) or after bariatric surgery), suboptimal responsiveness to exogenous erythropoietin (in chronic renal failure), in patients with cancer receiving chemotherapy, or when oral iron is poorly tolerated, IV iron therapy is the preferred mode of repletion. Although effective in increasing hemoglobin, the relative safety of the available IV iron preparations is not well documented. We examined the comparative safety of IV iron formulations used at hospitals associated with our institution. Among 619 unique patients who received IV iron over a 2-year period, we found 32 adverse events (AEs), ranging from urticaria to chest pain. There were no serious AEs or anaphylactic-type reactions. In a multivariate model, there was no difference in AE rates between low-molecular-weight iron dextran (LMWD) and ferric gluconate; however, iron sucrose had significantly higher odds ratio of AEs (OR = 5.7; 95% CI = 1.6–21.3). Our data suggest that AE rates with IV iron are acceptable. More widespread use of LMWD, in particular, which can be given safely as a total dose infusion (TDI), should be considered.

Topics: Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Male; Middle Aged; Multivariate Analysis; Retrospective Studies

New Medicare rules that set forth a revised reimbursement scheme for dialysis services will introduce significant changes for providers. The new rules will abandon the current system of separate reimbursement for drugs associated with the hemodialysis services, including erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron. These rules will "bundle" these agents and related laboratory tests into a single, case-mix adjusted composite rate. These bundling rules will be gradually phased-in, beginning in 2011. One of the primary effects of the new reimbursement policy will be to discourage over-utilization of ESAs that comprise nearly one-quarter of hemodialysis-related Medicare expenditures. As a result, hemodialysis providers will be challenged to make hemodialysis services more cost-effective, while ensuring that Medicare clinical performance measures are met and patient care is not compromised. i.v. iron has an integral role in making anemia care more cost-effective in the hemodialysis setting by improving measures of iron-deficiency anemia, maintaining necessary iron balance, and reducing the utilization of ESAs. This review discusses the potential benefits of i.v. iron in the management of hemodialysis patients with iron-deficiency anemia. It also focuses on the available i.v. iron options, particularly the established efficacy and safety profile of i.v. iron dextran compared with other i.v. iron formulations as well as cost considerations.

Topics: Anemia, Iron-Deficiency; Chemistry, Pharmaceutical; Dextrans; Drug Costs; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Iron Compounds; Iron-Dextran Complex; Medicare; Reimbursement Mechanisms; Renal Dialysis; Risk Adjustment; Safety; Sucrose; Treatment Outcome; United States

Intravenous (IV) iron is a necessary component of the anemia management plan for the hemodialysis patient. Despite the demonstrated benefits of IV iron, questions remain as to the most effective strategies for using IV iron to maintain target hemoglobin (Hb) levels, ensure adequate iron supply, and optimize erythropoiesis-stimulating agent (ESA) therapy. Significant questions also surround the extent of the serum ferritin marker to reliably guide IV iron treatment decisions. The recent Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) and DRIVE-II studies showed that improvements in Hb levels, iron status, and ESA responsiveness can be achieved with a repletion course of IV iron in patients with serum ferritin levels up to 1200 ng/mL. These studies also demonstrated that higher serum ferritin levels are a poor predictor of positive response to IV iron. We sought to apply the lessons learned from the DRIVE studies in our hemodialysis clinic. We designed this retrospective study to determine if regular, low-dose IV iron administered to patients with serum ferritin levels up to 1200 ng/mL could improve measures of anemia and iron status while optimizing the use of IV iron and ESAs.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Drug Monitoring; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Renal Dialysis; Retrospective Studies; Total Quality Management; Treatment Outcome

Use of parenteral iron for anemia management in dialysis patients has greatly increased. Exceeding hemoglobin target levels is not without risk, and whether parenteral iron administration contributes to exceeding targets has not been tested. The authors aimed to determine prevalence of parenteral iron administration and its contribution to exceeding hemoglobin target levels.. The authors performed a retrospective observational study of 149,292 hemodialysis patients using Centers for Medicaid & Medicare Services data. All patients were point prevalent on January 1, 2004; survived through June 30, 2004; had Medicare as primary payer; were treated with erythropoiesis stimulating agents (ESAs); and had valid hemoglobin values in April, May, and June, 2004.. Of the cohort, 58% received parenteral iron; use was more likely among men, whites, younger patients, and patients with end-stage renal disease as a result of diabetes. Age > 75 yr, African American and other races, baseline hemoglobin > 12 g/dl, higher ESA dose, and iron use in months 1 to 4 of the study period were independently associated with the risk of exceeding hemoglobin levels of 12, 13, and 14 g/dl. Receiving iron in month 4 of the study period showed the highest probability of exceeding targets (odds ratios 1.49, 1.43, 1.50 for hemoglobin levels 12, 13, 14 g/dl, respectively).. Parenteral iron use is prevalent, and although adequate iron stores are central to ESA response, iron use may contribute to exceeding recommended hemoglobin levels. Only data from a prospective trial can confirm this association.

Topics: Aged; Anemia, Iron-Deficiency; Centers for Medicare and Medicaid Services, U.S.; Drug Therapy, Combination; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Practice Guidelines as Topic; Renal Dialysis; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome; United States

A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hypersensitivity reaction to ferric gluconate. The decision was made to continue therapy; however, two modifications were made. The patient was given dexamethasone, diphenhydramine, and ibuprofen 1 hour before administering the third dose, and the infusion time was prolonged by 1 hour. Approximately 45 minutes after the infusion was completed, the patient developed hives on her arms and legs. At the patient's next clinic visit, it was decided that continuation of parenteral iron repletion was necessary, and the decision was made to attempt a challenge with iron sucrose. The patient was given dexamethasone 8 mg to be taken the night before and the morning of treatment. She successfully completed the iron repletion therapy with iron sucrose. Three parenteral iron products are available in the United States: iron dextran, sodium ferric gluconate complex, and iron sucrose. Iron dextran, the oldest of these products, carries the highest risk for hypersensitivity reactions. Available data suggest that either iron sucrose or ferric gluconate can be safely administered to patients with known hypersensitivity to iron dextran. Our patient's experience implies that it may be possible to safely administer iron sucrose to a patient with hypersensitivity to ferric gluconate. This finding has clinical implications and warrants confirmation in a larger population.

Topics: Aged; Anemia, Iron-Deficiency; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hispanic or Latino; Humans; Infusions, Intravenous; Injections, Intravenous; Self Administration; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Ferric Compounds; Hematinics; Hepcidins; Humans; Infusions, Intravenous; Iron-Dextran Complex; Molecular Weight

Topics: Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferritins; Follow-Up Studies; Hematinics; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Treatment Outcome

The prevalence of iron deficiency and its contribution to the anemia of end stage renal disease has been extensively studied, but much less is known about the role of iron deficiency in the pathogenesis of the anemia of chronic kidney disease in predialysis patients. All new hemodialysis patients entering a single hemodialysis unit between July 1999 and April 2002 were included in the study. The admission laboratory tests and the Health Care Financing Administration (HCFA) 2728 form were examined to determine the prevalence of erythropoietin use, anemia (Hb<11 g/dl), and iron deficiency (ferritin<100 ng/ml and transferrin saturation %<20%). In a second part of the study, the effect of intravenous iron gluconate replacement in patients with stage III & IV chronic kidney disease was examined. Anemia was present in 68% of all patients starting hemodialysis. Iron deficiency was a common feature occurring in 29% of patients taking erythropoietin (49% of all patients) and 26% of patients without erythropoietin (51% of all patients). Following the administration of intravenous iron gluconate to four patients, there was a significant rise in hemoglobin levels from 10.6+/-0.19 to 11.7+/-g/dl (p=0.02).. Iron deficiency is common in predialysis patients. Replenishing iron stores in anemic patients with chronic kidney disease significantly increases hemoglobin levels and should be considered as an integral part of the therapy for treating anemia in the predialysis population.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Ferric Compounds; Gluconates; Humans; Kidney Diseases

In vitro evidence suggests that different intravenous iron (i.v. Fe) preparations may be associated with different infection rates. This observational study was to determine if different bacteremia rates are associated with different types or amounts of i.v. Fe preparations.. This retrospective, single-center study was carried out from April 2001 November 2002, a period in which a global switch from ferric gluconate (FG) to iron sucrose (IS) occurred. During Period I (April 2001 - January 2002) FG was the only i.v. Fe administered in our hemodialysis unit. During Period II (February 2002 - November 2002) IS was the only i.v. Fe administered in our unit. Group A (n = 63) received hemodialysis during both Period I and Period II. Group B (n = 41) received hemodialysis either during Period I or Period II.. More bacteremic episodes occurred while IS than while FG was being administered. The adjusted bacteremia incidence rate ratios (IRRs) associated with use of IS vs. FG were 2.92 (95% CI, 1.01 - 8.5) and 2.84 (95% CI 1.32 - 6.09) in Groups A and B, respectively. The adjusted bacteremia IRRs associated with receiving > 2,000 mg of i.v. Fe were 2.42 (95% CI 1.03 - 5.6) and 1.54 (95% CI 0.43 - 5.69) in Groups A and B, respectively. Use of catheters as hemodialysis access increased bacteremia risk in both groups.. Use of iron sucrose is associated with higher bacteremia rates than ferric gluconate. The potential association between the cumulative amount of i.v. Fe administered and bacteremia risk is unclear. Randomized clinical trials are needed to verify our findings.

Topics: Aged; Anemia, Iron-Deficiency; Bacteremia; Chi-Square Distribution; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Poisson Distribution; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Statistics, Nonparametric

Topics: Anemia, Iron-Deficiency; Child; Ferric Compounds; Humans; Injections, Intravenous; Iron; Kidney Transplantation

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.

Topics: Adult; Alcohol Oxidoreductases; Anemia, Iron-Deficiency; Biomarkers; Drug Administration Schedule; Erythrocytes; Female; Ferric Compounds; Follow-Up Studies; Glutathione Peroxidase; Humans; Immunoenzyme Techniques; Injections, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Spectrophotometry; Superoxide Dismutase; Transferrin; Treatment Outcome

We report the first case of a severe anaphylactic or anaphylactoid reaction to sodium ferric gluconate complex in a pregnant patient. Sodium ferric gluconate complex is felt to be one of the safest forms of iron therapy during pregnancy. This case highlights the need for extreme caution and vigilance in pregnant patients receiving any type of parenteral iron therapy.

Topics: Adult; Anaphylaxis; Anemia, Iron-Deficiency; Drug Hypersensitivity; Female; Ferric Compounds; Humans; Infusions, Intravenous; Pregnancy; Pregnancy Complications, Hematologic

Many patients require parenteral iron therapy for optimal correction of anemia, including cancer patients who require erythropoietic drugs. Available parenteral iron therapy options include iron dextran, iron gluconate, and iron sucrose. The purpose of this study is to summarize our institution's experience with parenteral iron therapy over a 5-year period, with a focus on comparative safety profiles. All patients receiving parenteral iron therapy over this period were included in the analysis. Chi-squared test and Fisher's exact test were used to compare the adverse event rates of each product. A total of 121 patients received 444 infusions of parenteral iron over this period. Iron dextran was the most commonly used product (85 patients) and iron sucrose was the least used (2 patients). Iron gluconate was used by 34 patients. Overall adverse event rates per patient with iron dextran and iron gluconate were 16.5% and 5.8%, respectively (P = .024). Premedication with diphenhydramine and acetaminophen before infusions of iron dextran reduced adverse event rates per infusion from 12.3% to 4.4% (P = .054). Test doses of iron dextran were used 88% of the time for initial infusions of iron dextran. All adverse events for all parenteral iron products were mild or moderate. There were no serious adverse events and no anaphylaxis was observed. Our results suggest that, if test doses and premedications are used, iron dextran is an acceptable product to treat iron deficiency.

Topics: Acetaminophen; Anemia, Iron-Deficiency; Diphenhydramine; Female; Ferric Compounds; Ferric Oxide, Saccharated; Gastrointestinal Hemorrhage; Glucaric Acid; Humans; Infusions, Parenteral; Iron Metabolism Disorders; Iron-Dextran Complex; Kidney Diseases; Male; Menorrhagia; Neoplasms; Premedication; Retrospective Studies; Telangiectasia, Hereditary Hemorrhagic; United States; von Willebrand Diseases

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease patients. Therefore it is essential that serum ferritin levels should be maintened > 200 micro g/l. Functional iron deficiency occurs with serum ferritin levels > 200 micro g/l and transferrin saturation (TFS) lower than 20 %. The purpose of this study was to determine the efficacy of iron therapy in dialysis patients with serum ferritin levels higher than 200 micro g/l.. A total of 16 stable patients receiving chronic hemodialysis completed a 6-month survey period. Hemodialysis therapy and weekly subcutaneous rhEPO dose remained unchanged. Patients were divided into three groups according to their TFS, with TFS low (<20 %), barely adequate (20 % < TFS < 25 %) or optimal (>30 %). Sodium ferric gluconate complex (62.5 mg iron) was administered once per week intravenous over 10 minutes at the end of the dialysis.. After 3 months, hemoglobin was significantly higher in all groups (10.3 +/- 0.7 g/dl to 12,6 +/- 1.3 g/dl; p < 0,01) with no difference between the three groups and was constant in the following 3 months. Intravenous iron therapy raised ferritin levels significantly after 3 and 6 months: this observation was similar in all groups. The rise in TFS varied between and within the three groups.. Consistent intravenous iron therapy in combination with subcutaneous rhEPO had a rapid effect on the correction of anemia in patients with even optimal serum ferritin levels receiving chronic hemodialysis. There was no difference between patients with low, barely adequate and optimal TFS. It is concluded that there is a need for consistent intravenous iron therapy also in hemodialysis patients with optimal serum ferritin levels to correct anemia.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin; Treatment Outcome

Identical National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) hematologic and iron targets apply to chronic kidney disease (CKD), peritoneal dialysis (PD), and hemodialysis (HD) patients, yet intravenous (i.v.) nondextran iron therapy is FDA approved only in HD patients. This is because oral iron has been considered adequate in CKD and PD patients, and delivering a parenteral therapy on a frequent basis to an outpatient population with notoriously poor vascular access presents logistical complexities. However, recognition of the need for more aggressive treatment of anemia in the CKD and PD population is growing. This awareness, along with the improved safety profiles of the new, nondextran irons, is tipping the risk-benefit ratio toward more widespread use of i.v. iron in these patients. This article provides a summary of the literature and of our own experience using i.v. iron therapy in CKD and PD patients. Our protocol relies on early monitoring and intervention with i.v. ferric gluconate before severe iron deficiency develops. The proactive approach allows for relatively infrequent treatments at only moderately "high" doses (250 mg) of ferric gluconate. The convergence of convenience and safety may expedite more energetic anemia prevention and treatment in PD and CKD patients.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis

Ferric gluconate complex in sucrose (Ferrlecit) has been associated with less side-effects than iron dextran; however, the recommended dose of 62.5-125 mg per treatment is only suitable for haemodialysis (HD) patients. We retrospectively analysed the incidence of the side-effects associated with a high dose of Ferrlecit infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3-4 h, and 10 treatments of 500 mg/5 h infusion). The patients were in the age range of 32-75 years old, seven with chronic renal failure (CRF), and six on dialysis treatment. One (10%) of the 10 treatments using a 250 mg dose was complicated with severe nausea/vomiting, diarrhoea and a burning sensation in the feet. Three (30%) of the 10 treatments using a 500 mg dose were complicated with: chills, severe nausea/vomiting, hypotension and syncope in one; severe nausea/vomiting, diarrhoea and hypotension in one; and an episode of vomiting in one patient. A single treatment with a 250 mg dose resulted in no significant change in haematological parameters. A single treatment with a 500 mg dose resulted in a significant increase in haemoglobin (Hgb) and haematocrit (Hct), but only a rising trend in serum iron,% transferrin saturation and ferritin pre versus 1-2 months postinfusion. In conclusion, Ferrlecit doses of 250 or 500 mg are complicated with significant untoward reactions in 10-30% of patients, in a dose-dependent fashion.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Female; Ferric Compounds; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Severity of Illness Index

We hypothesized that intravenous iron will improve hemoglobin (Hgb) concentrations in anemic patients with chronic kidney disease (CKD), and the response would be greater if the underlying erythropoietin deficiency also was treated.. Charts of 58 CKD veterans (glomerular filtration rate < 80 mL/min) administered at least 125 mg of sodium ferric gluconate complex in sucrose (SFGC) during a period of 1 year for the primary outcome of an increase in Hgb level by at least 0.5 g/dL were reviewed.. Mean Hgb level at baseline was 10.5 +/- 1.4 (SD) g/dL (105 +/- 14 g/L) in the 30 patients administered recombinant human erythropoietin (rHuEPO) plus SFGC and 10.1 +/- 1.3 g/dL (101 +/- 13 g/L) in the 28 patients administered SFGC alone (P = not significant). The primary event occurred in 83% of the rHuEPO-plus-SFGC group at 31 days compared with 60% at 62 days in the group administered SFGC alone (P = 0.037, Cox F test). In patients administered SFGC alone, mean maximal Hgb level was 11.4 +/- 0.9 g/dL (114 +/- 9 g/L) in contrast to 12.4 +/- 1.7 g/dL (124 +/- 17 g/L) in the combination group, which remained significantly different even after adjustment for biologically important covariates (P = 0.01, analysis of covariance). Of the 240 doses of SFGC administered for which infusion records were available, 237 doses were well tolerated; three hypotensive episodes occurred in 2 patients, which did not result in discontinuation of the drug in either case.. Correction of anemia with parenteral iron alone suggests a high prevalence of iron deficiency in patients with CKD. Treatment of concomitant iron deficiency with SFGC was well tolerated in patients with CKD and appears to optimize management of anemia.

Topics: Administration, Oral; Aged; Anemia, Iron-Deficiency; Clinical Pharmacy Information Systems; Databases as Topic; Drug Administration Schedule; Erythropoietin; Female; Ferric Compounds; Glomerular Filtration Rate; Humans; Hypotension; Iron; Kidney Failure, Chronic; Male; Medical Records; Recombinant Proteins; Retrospective Studies; Sucrose; Treatment Outcome; Veterans

This report describes the safety and efficacy of high-dose sodium ferric gluconate in 18 peritoneal dialysis (PD) patients. Nine patients received low-dose (125 mg) and 9 patients received high-dose (250 mg) sodium ferric gluconate once per week for 8 or 4 weeks, respectively, followed by a maintenance dose once every 4 weeks. Patients in both groups had low iron saturation before treatment (hemoglobin [Hgb] < 11 g/dl, transferrin saturation [TSAT] approximately 20%, and serum ferritin < 250 ng/ml). After treatment, TSAT and ferritin significantly increased in both the low-dose (ferritin 465 +/- 292 ng/ml and TSAT 33.5 +/- 6.9%) and high-dose (ferritin 622 +/- 339 ng/ml and TSAT 35.0 +/- 25.7%) groups compared to baseline. Hemoglobin levels also increased in both groups, but this was not statistically significant. No adverse reactions or transferrin oversaturation with high-dose sodium ferric gluconate were observed. In conclusion, high-dose sodium ferric gluconate was safe, convenient, and effective in treating iron deficiency in PD patients.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferritins; Humans; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Retrospective Studies

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Renal Dialysis; Sucrose; Terminology as Topic

This is not a controlled study but an anecdotal experience that resulted in improved outcomes in a patient with multiple allergies, including iron dextran. Target Hct/Hgbs were attained and exceeded, although iron indices were not fully achieved. Infections demonstrated RE blockade and failure of TSAT to reach target range. The multidisciplinary team's successful decision to trial SFG in a medically complex patient allowed profound iron deficiency to be treated safely and effectively, which was not possible prior to the availability of an alternate iron preparation. It is rewarding to have the option to offer a medication that improves patients' status and enhances outcomes. Mr. C. was less tired and had more energy following his first and subsequent courses of therapy. "I couldn't believe how tired I was without realizing it until after I finished a course of iron therapy. I just thought that was my quality of life on dialysis. It's much better now and I have more energy." Such comments justify our efforts on our patients' behalf.

Topics: Adult; Anemia, Iron-Deficiency; Drug Combinations; Drug Hypersensitivity; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Patient Care Planning; Renal Dialysis; Sucrose; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Ferric Compounds; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Transferrin; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Humans; Infusions, Intravenous; Renal Dialysis; Transferrin

Topics: Anemia, Iron-Deficiency; Cytokines; Erythropoietin; Ferric Compounds; Ferritins; Humans; Iron; Renal Dialysis; Uremia

Zinc protoporphyrin (ZPP), a metabolic intermediate generated in the red blood cell by incorporation of zinc instead of iron, has been suggested to be a sensitive and specific parameter of absolute iron deficiency in haemodialysis (HD) patients.. We studied 62 HD patients, 29-86 years old, with ZPP levels > 50 mumol/mol haeme (normal value of ZPP < 40 mumol/mol haeme) assessing the value of ZPP as a marker of functional iron deficiency at different cut-off points of ZPP. None of the patients had apparent inflammatory disease, infectious disease, or malignancy. ZPP, haemoglobin, iron and ferritin levels were determined before, and after a 24-week period of once-weekly i.v. administration of 40 mg iron, to determine whether ZPP levels return to normal during adequate iron supplementation (960 mg iron/ patient).. There was no significant change in ZPP levels after iron supplementation in patients with a ZPP > 50 mumol/mol haeme (96.7 +/- 49.8 versus 88.4 +/- 43.5 mumol/mol haeme before and after iron administration respectively, P = n.s.). However, in patients with a ZPP > 90 mumol/mol haeme, there was a significant reduction in ZPP levels (141.2 +/- 54.5 versus 108.0 +/- 48.8 mumol/mol haeme, P < 0.001). Serum ferritin increased significantly in both groups. There was no correlation between ZPP and serum ferritin at any time during the study. There was also no correlation between serum aluminium levels and ZPP and no significant difference in changes in ZPP in patients receiving desferrioxamine therapy compared to those not receiving desferrioxamine therapy. We did find a significant correlation between moderately elevated total blood lead concentrations and ZPP levels at the end of the study. The ZPP levels were not significantly different in the range from 50-110 mumol/mol haeme before and after i.v. iron supplementation in the responders (10% increase of haemoglobin or 20% decrease of the recombinant human erythropoietin dose) compared with the non-responders.. Our data indicate that ZPP cannot be used to predict the erythropoietic response to iron supplementation. However, ZPP levels may be an indicator of functional iron deficiency due to blockade of the reticuloendothelial iron release in haemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Enzyme Inhibitors; Erythrocytes; Erythropoiesis; Female; Ferric Compounds; Ferritins; Heme Oxygenase (Decyclizing); Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Protoporphyrins; Regression Analysis; Renal Dialysis