ferlixit and Anemia

A number of intravenous iron formulations have been developed over the past 65 years which rely on dextran or other compounds to prevent uncontrolled release of free iron to the circulation. High molecular weight dextran was associated with a number of serious adverse reactions and was removed from markets worldwide in 2009. The preponderance of published evidence suggests that the formulations of parenteral iron currently available in the United States, including low molecular weight iron dextran, are all safe and effective and there are no major, clinically important differences among them in terms of either efficacy or safety. For patients with chemotherapy induced anemia or with anemia of end stage renal disease who are being treated with hemodialysis, it is reasonable to use any of the iron formulations, including iron sucrose and ferric gluconate, as frequent patient encounters with health caregivers are a routine part of care and the need to administer multiple low doses of IV iron is not a major disadvantage. However, a single infusion of a total iron dose is as effective and safe when giving iron preparations containing low molecular weight iron dextran, ferumoxytol, iron isomaltoside, or ferric carboxymaltose. Use of a single total dose infusion results in a decreased number of intravenous infusions with a lower cumulative risk for infusion reactions or extravasations, a reduced need for multiple office visits and repeated utilization of medical staff, and increased convenience for physicians and patients.

Topics: Anemia; Drug Compounding; Ferric Compounds; Ferrosoferric Oxide; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Maltose; Renal Dialysis

The prevention of anemia of blood donor is a main issue for donor safety and self-supplying. This prevention is done in one hand by donor deferral whose haemoglobin level is under defined threshold and in other hand by preventing iron deficiency. Some subgroups of donors are at increased risk for developing iron deficiency and adverse effects of iron deficiency: premenopausal females; donors with haemoglobin values near the minimum for eligibility and frequent donors. Different interventions could be used: lengthening the inter-donational interval and/or decreasing the number of donations per year; donor ferritin testing to evaluate iron store and at least donor iron supplementation.

Topics: Anemia; Blood Donors; Donor Selection; Female; Ferric Compounds; Ferritins; Hemoglobins; Humans; Iron Deficiencies; Male; Premenopause; Risk Factors; Sex Characteristics; Time Factors

Intravenous iron (IV Fe) as an adjunct to therapy with erythropoiesis- stimulatory agents (ESAs) is standard care in dialysis-associated anemia, adding huge increments in hemoglobin and hematopoietic responses and decreased transfusions without significant toxicity. Cost savings, decreased exposure to ESAs, and decreased times to reach target hemoglobins are realized. Although similar benefits have been seen in all studies performed in patients with chemotherapy-induced anemia (CIA), experts are reluctant to incorporate routine use of IV Fe into treatment, largely because of misinterpretation and misunderstanding of the clinical nature of adverse events reportedly associated with its administration. IV Fe is therefore underused in oncology patients with anemia. Published experience with more than 1000 patients in clinical trials involving the use of IV Fe suggests minimal toxicity and substantial benefit are experienced when high molecular weight iron dextran is avoided. This article presents evidence recommending routine incorporation of IV Fe into treatment for CIA.

Topics: Anemia; Antineoplastic Agents; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Injections, Intravenous; Iron-Dextran Complex; Neoplasms

Patients with cancer may have an absolute or functional iron deficiency as a result of their disease or its treatment. These conditions can lead to an insufficient supply of iron for incorporation into erythrocytes during supportive care with erythropoiesis-stimulating proteins for chemotherapy. The use of supplemental iron therapy is well established in patients with chronic kidney disease and anemia, but less well studied in the oncology/hematology setting. Furthermore, the use of oral iron formulations in patients with cancer and anemia is limited by poor absorption in the duodenum, arduous dosing requirements (three times a day), and a high likelihood of gastrointestinal side effects. Two recent studies have shown that intravenous (i.v.) iron (iron dextran or ferric gluconate) increases the hematopoietic response rates in cancer patients who were receiving chemotherapy and treated with epoetin alfa (Procrit) for anemia. The effects on hemoglobin levels and measures of iron metabolism were notably greater with i.v. iron formulations than with oral iron formulations. The results from several ongoing trials of i.v. iron in patients treated with epoetin alfa or darbepoetin alfa (Aranesp) for chemotherapy-induced anemia should lead to a greater understanding of the role of i.v. iron supplementation in improving the hematopoietic responses in these patients.

Topics: Anemia; Antineoplastic Agents; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Neoplasms

In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non-transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with caution but its use should not be feared whenever indicated.

Topics: Anemia; Cytokines; Endothelial Cells; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Gluconates; Hematinics; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Neutrophils

This is a post-hoc analysis evaluating erythropoiesis stimulating agents' (ESA) related costs while using an additional ultrafilter (Estorclean PLUS) to produce ultrapure dialysis water located within the fluid pathway after the treatment with reverse osmosis and before the dialysis machine. Twenty-nine patients (19 treated with epoetin alfa and 10 with darboepoetin alfa) were included in the analysis. We showed to gain savings of 210 € per patient (35 € per patient each month) with epoetin alfa during the experimental period of 6 months, compared to the control period and of 545 € per patient (90 € per patient each month) with darboepoetin alfa. Estorclean PLUS had a cost of 600 € (25 € per month per each patient) and was used for 6 months. Intravenous iron therapy with sodium ferrigluconate had a cost of 0,545 €/62,5 mg. In conclusion, during the experimental period with the use of Estorclean, we obtained global savings of 11 € per patient per month with epoetin alfa and 30 € per patient per month with darboepoetin alfa to treat anemia in dialysis patients.

Topics: Aged; Aged, 80 and over; Anemia; Cost Savings; Costs and Cost Analysis; Cross-Over Studies; Darbepoetin alfa; Distillation; Epoetin Alfa; Female; Ferric Compounds; Filtration; Hematinics; Hemodialysis Solutions; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Water

Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA.. This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks.. There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb ≥ 12 g/dL or Hb increase ≥ 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16).. In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo.

Topics: Administration, Oral; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies

Advanced-stage cancer patients often suffer from anemia that closely resembles the anemia of chronic inflammatory diseases characterized by specific changes in iron homeostasis and absorption. i.v. iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. We report the results of an open-label, randomized, prospective trial aimed at testing the efficacy and safety of treatment with oral lactoferrin versus i.v. iron, both combined with rHuEPO, for the treatment of anemia in a population of 148 advanced cancer patients undergoing chemotherapy. All patients received s.c. rHuEPO-beta, 30,000 UI once weekly for 12 weeks, and were randomly assigned to ferric gluconate (125 mg i.v. weekly) or lactoferrin (200 mg/day). Both arms showed a significant hemoglobin increase. No difference in the mean hemoglobin increase or the hematopoietic response, time to hematopoietic response, or mean change in serum iron, C-reactive protein, or erythrocyte sedimentation rate were observed between arms. In contrast, ferritin decreased in the lactoferrin arm whereas it increased in the i.v. iron arm. In conclusion, these results show similar efficacy for oral lactoferrin and for i.v. iron, combined with rHuEPO, for the treatment of anemia in advanced cancer patients undergoing chemotherapy.

Topics: Administration, Oral; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Female; Ferric Compounds; Hemoglobins; Humans; Lactoferrin; Male; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

Topics: Adult; Aged; Anemia; Drug Interactions; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation (TSAT). The Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) trial was designed to evaluate the efficacy of intravenous ferric gluconate in such patients. Inclusion criteria were hemoglobin or=225 IU/kg per wk or >or=22,500 IU/wk. Patients with known infections or recent significant blood loss were excluded. Participants (n=134) were randomly assigned to no iron (control) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions (intravenous iron). At randomization, epoetin was increased 25% in both groups; further dosage changes were prohibited. At 6 wk, hemoglobin increased significantly more (P=0.028) in the intravenous iron group (1.6 +/- 1.3 g/dl) than in the control group (1.1 +/- 1.4 g/dl). Hemoglobin response occurred faster (P=0.035) and more patients responded after intravenous iron than in the control group (P=0.041). Ferritin 800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group. Similarly, the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19%. Ferritin decreased in control subjects (-174 +/- 225 ng/ml) and increased after intravenous iron (173 +/- 272 ng/ml; P<0.001). Intravenous iron resulted in a greater increase in TSAT than in control subjects (7.5 +/- 7.4 versus 1.8 +/- 5.2%; P<0.001). Reticulocyte hemoglobin content fell only in control subjects, suggesting worsening iron deficiency. Administration of ferric gluconate (125 mg for eight treatments) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT

Topics: Anemia; Female; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Male; Middle Aged; Renal Dialysis; Transferrin

To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa.. In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal.. One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase > or =2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated.. For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.

Topics: Administration, Oral; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

Intravenous (i.v) iron is widely used to treat anaemia in patients with chronic kidney disease (CKD). Although beneficial and usually well tolerated, concerns have been raised about its ability to cause oxidative stress and renal injury.. To determine if i.v. iron causes oxidative stress [as assessed by plasma and urine malondialdehye (MDA)] and/or renal injury (as assessed by urinary albumin, total protein and enzymuria), we conducted a prospective, four-way randomized crossover, blinded end-point trial in eight patients with CKD. Two widely used doses of sodium ferric gluconate (125 mg infused over 1 h and 250 mg infused over 2 h) were given with or without the antioxidant N-acetylcysteine (NAC), resulting in four treatment dose-antioxidant/placebo combinations in each patient. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, MDA by high performance liquid chromatography, and albuminuria and proteinuria by standard clinical methods. Enzymuria was assessed by measurement of N-acetyl-beta-D-glucosaminidase (NAG) excretion by colorimetric assay.. I.v. ferric gluconate infusion at both doses resulted in a marked increase in transferrin saturation and a significant increase in plasma MDA levels. Urinary MDA levels also increased at the higher dose of iron. There was no evidence of acute renal injury, as assessed by albuminuria, proteinuria or enzymuria. Pre-treatment with NAC had no effect on oxidative stress or the above urinary parameters.. I.v. ferric gluconate caused oxidative stress (as reflected by increased MDA), but this was not associated with biochemical manifestations of acute renal injury.

Topics: Acetylcysteine; Acute Kidney Injury; Aged; Aged, 80 and over; Analysis of Variance; Anemia; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Ferric Compounds; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Kidney Function Tests; Male; Malondialdehyde; Oxidative Stress; Pilot Projects; Probability; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method

Topics: Anemia; Bloodless Medical and Surgical Procedures; Female; Ferric Compounds; Hematinics; Humans; Hyperbaric Oxygenation; Infusions, Intravenous; Jehovah's Witnesses; Leiomyoma; Medroxyprogesterone; Middle Aged; Patient-Centered Care; Uterine Hemorrhage; Uterine Neoplasms

Intravenous iron is one of the main therapies for anemia management in hemodialysis-dependent patients. Data comparing the efficacy of ferumoxytol versus other parenteral iron supplements are scarce. The objective of the study was to compare the efficacy of ferumoxytol with that of sodium ferric gluconate in outpatient hemodialysis patients.. A prospective, observational study was conducted in outpatients receiving ferumoxytol 510 mg once or twice quarterly compared to sodium ferric gluconate 125 mg weekly in a single center hemodialysis center in Ontario, Canada. Patient demographics, hemoglobin levels, iron indices, iron doses, and erythropoiesis-stimulating agent (ESA) doses were collected.. The study sample consisted of 291 observations from 173 patients. Generalized estimating equations of multiple linear regression modeling were conducted to compare the outcomes while adjusting for baseline scores. Approximately 25% of the study participants received ferumoxytol while 75% received sodium ferric gluconate. Patients treated were mainly males (58.4%), and the mean age was 68.73 (SD ± 13.03) years. Both groups did not show significant differences in their hemoglobin levels (Wald z = 0.54; p = 0.46), ESA utilization at 3 months (Wald z = 0.20; p = 0.65), and TSAT levels (Wald z = 3.45; p = 0.06). However, the iron levels (Wald z = 4.24; p = 0.04) and ferritin levels (Wald z = 5.14; p = 0.02) were higher in the ferric gluconate group (Wald z = 58.78; p ≤ 0.001), and patients who received ferumoxytol received more blood transfusions as compared to those who received sodium ferric gluconate (χ. Both iron products maintained hemoglobin levels, but patients receiving ferumoxytol had lower iron indices and received more blood transfusions compared to patients who received sodium ferric gluconate.

Topics: Aged; Aged, 80 and over; Anemia; Blood Transfusion; Female; Ferric Compounds; Ferrosoferric Oxide; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome

Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex.. Retrospective cohort study of incident HD patients.. Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure.. Facility-level use of iron sucrose versus ferric gluconate.. Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths.. HRs.. We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96).. Unobserved selection bias from nonrandom treatment assignment.. Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.

Topics: Administration, Intravenous; Aged; Anemia; Cardiovascular Diseases; Cause of Death; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infections; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Proportional Hazards Models; Renal Dialysis; Retrospective Studies

Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD).. Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)].. In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups.. In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG.

Topics: Administration, Intravenous; Aged; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Prognosis; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; United States

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

Topics: Anemia; Antineoplastic Agents; Ferric Compounds; Humans; Iron; Patient Dropouts; Randomized Controlled Trials as Topic; Transferrin

Sodium ferric gluconate in complex (SFG) is used to treat iron deficiency anemia in patients aged ≥6 years undergoing chronic hemodialysis and receiving supplemental epoetin therapy. Both the branded product (Ferrlecit, branded SFG) and a new generic version of sodium ferric gluconate in complex (Nulecit; generic SFG) are provided in 5 mL vials. SFG may be administered by slow intravenous (IV) injection of the undiluted product or by 1 h IV infusion after dilution in 100 mL 0.9% sodium chloride. This study evaluated the short-term stability of undiluted and diluted generic SFG at room temperature and under refrigeration.. Samples of generic SFG undiluted in 10 mL syringes or diluted in IV infusion bags containing 0.9% sodium chloride solution were stored at room temperature or under refrigerated conditions (2-8°C). Samples at room temperature were stored for ≤48 h if undiluted and for ≤24 h if diluted. All refrigerated samples were stored for ≤7 days. Parameters evaluated were elemental iron (Fe) concentration and SFG apparent molecular weight. All tests were performed on two lots of the generic product.. Fe concentrations were identical in both lots and did not vary substantially over time under different conditions of storage or dilution. SFG apparent molecular weight varied across all samples from 306,000 to 354,000 Daltons, well within the range of 289,000 to 440,000 Daltons specified as the molecular weight in the FDA-approved prescribing information.. Iron content and SFG apparent molecular weight were stable under all experimental conditions. Undiluted generic SFG was stable for ≥2 days at room temperature and ≥7 days under refrigerated conditions, and generic SFG diluted in IV infusion bags containing 0.9% sodium chloride solution was stable for ≥1 day at room temperature and ≥7 days under refrigerated conditions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Child; Drug Stability; Drugs, Generic; Female; Ferric Compounds; Hematinics; Humans; Male; Middle Aged; Sucrose; Sweetening Agents

Intravenous iron supplementation is a basic principle in the therapy of haemodialysis (HD) patients with renal anaemia. In the Iron Dextran in Renal Anaemia (IDIRA) study, we analysed the efficacy of a therapy with low-molecular-weight iron dextran (LMW-ID) in stable HD patients with adequate iron stores previously treated with ferric gluconate.. IDIRA was an open-label, prospective, non-randomized, observational multicenter trial over 12 months in iron-repleted HD patients. All patients were treated with intravenous LMW-ID. Measures of efficacy were changes of haemoglobin (Hb), serum ferritin, erythropoietin dose and the response to iron therapy calculated as ferritin efficacy and Hb efficacy. Statistical analysis was done by the Wilcoxon test.. A total of 221 HD patients with a mean age 63.7 +/- 13.8 years were included. A total of 208 out of 221 patients were on erythropoietin therapy. Median time on dialysis was 2 (1-4) years. Mean Kt/V was 1.3. Of the 221 patients, 208 completed the 12-month study period. Mean Hb and serum ferritin increased without the need for higher erythropoietin doses. The mean amount of iron per week administered remained stable. Ferritin efficacy and Hb efficacy improved using LMW-ID (p < 0.01).. We conclude that LMW-ID improves anaemia management even in iron-pretreated HD patients.

Topics: Aged; Anemia; Darbepoetin alfa; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematinics; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.. The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.. Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) microg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1-202 mg/month, slightly worse with 202-455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation < or = 16%, serum ferritin < or = 100 microg/L, best with transferrin saturation > 25%, serum ferritin > 600 microg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.. Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.

Topics: Adult; Aged; Anemia; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Survival Analysis; Transferrin

The effects of i.v. iron formulations on serum ferritin concentration (SFC) and transferrin saturation (TSAT) are compared in adult hemodialysis patients with anemia receiving erythropoiesis-stimulating agents (ESAs).. This study consisted of 215 patients who were receiving chronic hemodialysis, ESAs, and i.v. iron supplementation from November 2005 to November 2006. All patients received iron sucrose therapy from November 2005 to April 2006. Patients were then switched to sodium ferric gluconate. If the patient's SFC was <100 ng/mL and TSAT was <20%, then iron sucrose 100 mg i.v. at every hemodialysis for 10 doses or sodium ferric gluconate 125 mg i.v. at every hemodialysis for 8 doses was administered as loading doses. Maintenance doses of iron sucrose 60 mg or sodium ferric gluconate 62.5 mg were administered every two weeks if the SFC was 100-499 ng/mL and the TSAT was 20-29% or every four weeks if the SFC was 500-600 ng/mL and the TSAT was 30-45%. SFC and TSAT were measured every three months.. More treatment courses resulted in target SFC and TSAT values during treatment with sodium ferric gluconate than iron sucrose, but neither difference was significant. The proportion of treatment courses resulting in SFCs of >600 ng/mL (above the target range) was significantly greater during treatment with iron sucrose than sodium ferric gluconate.. There was no significant difference between iron sucrose and sodium ferric gluconate in the frequency in which SFC and TSAT values were within target ranges in hemodialysis patients with anemia receiving ESAs. Of the two drugs, iron sucrose was more likely to produce an SFC above the target range.

Topics: Adult; Anemia; Cohort Studies; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Renal Dialysis; Retrospective Studies; Transferrin

Clinicians who manage anemia in patients with chronic kidney disease, both on and off dialysis therapy, face several challenges: maintain stable hemoglobin (Hb) levels in their patients, avoid overshooting Hb targets, balance intravenous (IV) iron and erythropoiesis-stimulating agents (ESAs), and improve ESA response to use the lowest effective ESA dose. Special attention to ESA hyporesponsiveness, as well as the role of insufficient iron, is required. The efficacy of IV iron in managing these challenges, particularly in hemodialysis patients who have anemia despite adequate ESA doses, was shown in the randomized controlled Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) clinical trial and its 6-week follow-up extension study, DRIVE-II. These studies provide suggestive evidence of the ability of IV iron to reduce ESA requirements and maintain improved Hb levels in anemic hemodialysis patients with serum ferritin levels of 500 to 1,200 ng/mL and transferrin saturations of 25% or less.

Topics: Anemia; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ferric Compounds; Guidelines as Topic; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Renal Dialysis; United States; United States Food and Drug Administration

A subgroup of hemodialysis patients experience high serum ferritin and low tansferrin saturation for reasons not clearly understood. Here we determined the economic impact of administering sodium ferric gluconate complex to patients with serum ferritin levels higher than 500 ng/ml and a transferrin saturation less than 25% based on the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study and its extension, DRIVE II. A cost effectiveness model was developed, consistent with the DRIVE studies, using decision analysis with a 12-week time horizon. The primary effectiveness measure was the mean hemoglobin increase in the intent to treat patient groups comparing epoetin with or without sodium ferric gluconate complex. Costs were computed using projected 2007 US Medicare reimbursements for the treatments and for serious adverse events, with the effectiveness factored by the increase in hemoglobin. The net savings for sodium ferric gluconate complex plus epoetin treatment was $1390 compared to epoetin alone for each g/dl hemoglobin increase over 12 weeks of study. Sensitivity analyses were performed to test the impact of change in the variables (using medians or means and actual 2005 or projected 2007 Medicare reimbursements) and these affirmed the robustness of the model. Our study shows that treatment of patients with high ferritin and low transferrin saturation levels, as defined in DRIVE, with sodium ferric gluconate complex and epoetin resulted in significant savings compared to epoetin alone.

Topics: Adult; Aged; Algorithms; Anemia; Cost Savings; Drug Costs; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Kidney Diseases; Medicare; Middle Aged; Recombinant Proteins; Renal Dialysis; United States

Topics: Anemia; Drug Approval; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Molecular Weight; Renal Dialysis; United States; United States Food and Drug Administration

Post-transplant anemia is a widespread problem among pediatric renal transplant recipients. Many clinicians treat post-transplant anemia in a manner similar to treatment of anemia in dialysis patients, including the use of intravenous iron, such as sodium ferric gluconate (SFG). Data on pediatric dosing of SFG are limited to rare small series containing few or no renal transplant recipients. We conducted a retrospective chart review of practice patterns at our institution to evaluate doses used, hemoglobin response and adverse events. We identified 15 renal transplant recipients who received SFG during the 28-month study period. Data from 14 of these patients were available for analysis. Patients received between one and six doses of SFG to yield a total dose of 100-1000 mg or 2.7-23.7 mg/kg. The largest doses given during a single infusion ranged from 1.9 to 6.4 mg/kg. The mean hemoglobin level increased from 101 +/- 16 to 114 +/- 21 g/L (p = 0.0092) following SFG therapy. Adverse events were recorded for three patients. Treatment with SFG appears to yield some improvement in anemia in renal transplant recipients, but the paucity of published information on this topic highlights the need for stronger data, particularly with respect to pediatric patients.

Topics: Adolescent; Adult; Anemia; Child; Erythropoietin; Female; Ferric Compounds; Hemoglobins; Humans; Injections, Intravenous; Kidney Transplantation; Male; Postoperative Complications; Recombinant Proteins; Retrospective Studies

Although maintenance of iron stores by intravenous iron infusion has become increasingly common in chronic hemodialysis patients, the effects of intravenous iron on blood pressure are not clear.. In 52 mostly African-American patients in an urban setting, we reviewed blood pressure data over the course of hemodialysis on days that intravenous iron was administered and on control days.. The drop in blood pressure from the beginning to the end of hemodialysis was more pronounced when iron was not administered (9.9 +/- 1.2 mm Hg) compared to when iron was administered (4.1 +/- 1.7 mm Hg; p < 0.01). In a subset of chronic hemodialysis patients, blood pressure was actually higher at the end of hemodialysis compared to at the onset (9.6% of control hemodialysis sessions and 32.7% of sessions in which iron was administered; p < 0.01). The incidence of intra-dialytic hypotension and related symptoms was similar on iron and non-iron days.. Intravenous iron therapy, well entrenched in clinical practice for the treatment of the anemia of end-stage renal disease, may reduce the incidence and magnitude of post-dialytic hypotension.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Pressure; Female; Ferric Compounds; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Anaemic haemodialysis (HD) patients are treated with erythropoietin and intravenous iron for effective erythropoiesis. Since iron is a potent inducer and aggravator of pre-existing oxidative processes in HD patients, this study was aimed to evaluate the acute in vivo effect of two recommended iron doses on protein oxidation during the HD session.. Iron gluconate was intravenously administered to HD patients in doses of 62.5 or 125 mg per session. A dialysis session without iron administration served as a control for each patient. Carbonylated fibrinogen and iron profile parameters were monitored before and after each session. Plasma carbonylated fibrinogen levels from healthy subjects and HD patients before dialysis were compared. Protein associated carbonyls were identified in plasma by derivatization with 2,4-dinitrophenylhydrazine followed by western analysis and were quantified by densitometry.. HD patients on maintenance iron showed elevated carbonylated fibrinogen compared with healthy subjects. During a HD session, carbonyls on fibrinogen further increased when 125 mg iron gluconate was administered, but no changes were detected with 62.5 mg iron gluconate or in the absence of iron. The changes in carbonylated fibrinogen during dialysis showed a significant linear correlation with the calculated values of transferrin saturation and free transferrin.. The significant acute increase in carbonylated fibrinogen with 125 mg iron gluconate suggests that this iron dose should be used with caution. As fibrinogen is highly susceptible to iron-induced oxidation in vivo, it may serve as a marker reflecting acute iron oxidative damage and as a tool in refinement of the existing clinical dose guidelines for intravenous iron therapy.

Topics: Aged; Aged, 80 and over; Anemia; Case-Control Studies; Erythropoietin; Female; Ferric Compounds; Fibrinogen; Humans; Male; Middle Aged; Oxidative Stress; Recombinant Proteins; Renal Dialysis; Transferrin

Topics: Aged; Aged, 80 and over; Anemia; Cost-Benefit Analysis; Drug Costs; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Spain; Sucrose

Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO).. The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition.. A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment.. The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Topics: Aged; Anemia; Biomarkers; C-Reactive Protein; Epidemiologic Methods; Erythropoietin; Female; Ferric Compounds; Humans; Inflammation; Interleukin-6; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Male; Malnutrition; Middle Aged; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Sex Factors; Syndrome; Tumor Necrosis Factor-alpha

Erythropoietin (Epo) is an effective but expensive treatment for anaemia in patients with chronic renal failure. Hyporesponsiveness to Epo, particularly in haemodialysis patients, is most commonly due to a functional iron deficiency, which is difficult to monitor reliably.. Forty-six stable haemodialysis patients, receiving Epo therapy, were commenced on regular low-dose intravenous iron (sodium ferric gluconate complex) at a dose of 62.5 mg/5 ml given as a slow injection post-dialysis twice weekly, weekly, or fortnightly, according to their serum ferritin levels. Haemoglobin, serum ferritin, Epo dose, and iron dose were measured at 6-weekly intervals over a 6-month period.. At the beginning of the study, 12 patients in the group had ferritin levels of less than 100 microg/l, and were thus considered to potentially have an absolute iron deficiency. The study group was therefore split into two subgroups for the purpose of analysis, i.e. the 12 patients with ferritin levels of less than 100 microg/l at the start of the study or 'low ferritin group', and the remaining 34 patients with ferritin levels of greater than 100 microg/l at the start of the study or 'normal ferritin group'. In the low ferritin group (n=12), intravenous iron therapy increased serum ferritin levels, and produced a significant rise in haemoglobin, and a significant reduction in Epo dose. (Ferritin pre-iron, median (range) 68 (20-96) microg/l; post-iron, 210.5 (91-447) microg/l, P<0. 003, Wilcoxon. Haemoglobin pre-iron, 10.05 (8.2-11.9) g/dl; post-iron, 11.0 (9.9-11.9) g/dl, P<0.03. Epo dose pre-iron, 9000 (4000-30 000)-i.u./week, P<0.05). Similar results were obtained in the normal ferritin group (n=34) following intravenous iron therapy, with significant increases in serum ferritin levels and haemoglobin concentrations, and a significant reduction in Epo dose. (Ferritin pre-iron, 176 (103-519) microg/l; post-iron, 304.5 (121-792) microg/l, P<0.0001. Haemoglobin pre-iron, 9.85 (6.5-12.8) g/dl; post-iron: 11.25 (9.9-13.3) g/dl, P<0.0001. Epo dose pre-iron, 6000 (2000-15 000) i.u./week; post-iron, 4000 (0-15 000)-i.u./week, P<0. 005).. Regular intravenous iron supplementation in haemodialysis patients improves the response to Epo therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Drug Synergism; Erythropoietin; Female; Ferric Compounds; Ferritins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

It is not known whether recombinant human erythropoietin has a direct, clinically apparent pressor effect in hemodialysis patients or whether hypertension developing or aggravated in these patients merely reflects increased hematocrit. We compared blood pressure after three different methods of partial correction of anemia in hemodialysis patients with similar baseline hematocrits (erythropoietin n = 12, intravenous iron alone n = 10, androgens n = 9). Shortly after the start of treatment and with a minimally increased hematocrit, the need for antihypertensive medication increased in the erythropoietin group. No such pressor effect was observed with iron or androgens. These data suggest a direct hypertensive effect of erythropoietin in some patients on hemodialysis.

Topics: Adult; Anemia; Blood Pressure; Erythropoietin; Female; Ferric Compounds; Humans; Hypertension; Male; Middle Aged; Nandrolone; Nandrolone Decanoate; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Biomedical Research; Child; Cobalt; Ferric Compounds; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Iron