Comparison of efficacy and safety of two parenteral iron preparations in pregnant women Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study Safety and Efficacy of Intravenous Ferric Carboxymaltose (750 mg) in the Treatment of Iron Deficiency Anemia: Two Randomized, Controlled Trials Darbepoetin alfa 300 or 500 μg once every 3 weeks with or without intravenous Iron in patients with chemotherapy‐induced anemia A Randomized, Open-Label, Non-Inferiority Study of Intravenous Iron Isomaltoside 1,000 (Monofer) Compared With Oral Iron for Treatment of Anemia in IBD (PROCEED) Safety and Usefulness of Intravenous Iron Sucrose in the Management of Preoperative Anemia in Patients with Menorrhagia: A Phase IV, Open-Label, Prospective, Randomized Study Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. The safety of achieved iron stores and their effect on IV iron and ESA use: post-hoc results from a randomized trial of ferric citrate as a phosphate binder in dialysis . Intravenous iron isomaltoside improves hemoglobin concentration and iron stores in female iron‐deficient blood donors: a randomized double‐blind placebo‐controlled clinical trial A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. Efficacy and safety of intravenously administered iron sucrose with and without adjuvant recombinant human erythropoietin for the treatment of resistant iron-deficiency anemia during pregnancy. A Randomized Noninferiority Trial of Intravenous Iron Isomaltoside versus Oral Iron Sulfate in Patients with Nonmyeloid Malignancies and Anemia Receiving Chemotherapy: The PROFOUND Trial Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney disease: a randomized, active-controlled, multi-center study. A Phase III, randomized, open-label trial of ferumoxytol compared with iron sucrose for the treatment of iron deficiency anemia in patients with a history of unsatisfactory oral iron therapy Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations. Clinical update: intravenous iron for anaemia Intravenous Iron Sucrose in Peritoneal Dialysis Patients with Renal Anemia A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia.
Objective : To compare the efficacy and safety with a fixed dose of two parenteral iron preparations , iron sucrose complex and iron sorbitol citric acid as per the current practice . Material s and Methods : A prospect i ve r and omized open label study was conducted . In this study , 60 pregnant women with hemoglobin less than 8.5 g/dl received a fixed dose of either IV iron sucrose or IM iron sorbitol citric acid therapy . The efficacy of the therapy was assessed by laboratory parameters such as hemoglobin , hematocrit , MCV , MCH , and serum ferritin level after 14 and 28 days . To assess the safety , adverse drug reactions with both the therapies were recorded . Results : Hemoglobin concentration increased significantly ( P < 0.001 ) with respect to time in both the groups . The rise in the hemoglobin level in third and fourth weeks was significantly higher in iron sucrose ( 0.92 g/dl ) than iron sorbitol citric acid therapy ( 0.56 g/dl ) . There was no significant change in the rise of the serum ferritin level after both the therapies . Adverse events were common with iron sorbitol citric acid therapy . However , no serious adverse drug reactions were observed . Conclusions : No significant difference in the efficacy of both of the therapy . However , adverse events and dropout rates were much more common in the group of pregnant women who received iron sorbitol citric acid Background Intravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective , but with possible adverse effects . Currently , prospect i ve studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents . Methods We conducted a prospect i ve , double-blind , r and omized controlled trial ( RCT ) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran , Infufer ® , with intravenous iron sucrose , Venofer ® , in non-hemodialysis adult out patients . Primary outcome was the occurrence of immediate severe drug reactions . Results We enrolled 143 patients in a one-year period . Overall , 45/143 ( 31.5 % ) patients ( 20 iron dextran , 25 iron sucrose ) developed 48 infusion reactions ( 14 immediate , 28 delayed , and 3 both ) . The risk of an immediate reaction was similar in both groups , 9/73 ( 12.3 % ) iron dextran versus 8/70 ( 11.4 % ) iron sucrose , RR = 0.93 ( 95 % CI ; 0.38 to 2.27 ) . The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 ( 31.4 % ) versus the iron dextran group 9/73 ( 12.3 % ) , RR = 2.55 ( 95 % CI ; 1.26 to 5.15 ; p = 0.0078 ) . Conclusion In this limited feasibility study , no major differences in immediate reactions were seen , but a significantly higher number of delayed reactions were seen in the iron sucrose group . Further , under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible . Future studies should consider modifying the clinical outcomes , utilize multiple centers , and consider other emerging parenteral iron formulations . ( Clinical Trials.gov NCT005936197 January 3 , 2008 ) Background . Iron deficiency anemia ( IDA ) is a common hematological complication with potentially serious clinical consequences that may require intravenous iron therapy . Ferric carboxymaltose ( FCM ) is a stable , nondextran iron formulation administered intravenously in large single doses to treat IDA . Objective . Two open-label , r and omized , placebo-controlled trials evaluated safety of multiple or single 750 mg FCM doses compared to st and ard medical care ( SMC ) in IDA patients . Secondary endpoints were improvements in hemoglobin and iron indices . Design and Patients . Adults with hemoglobin ≤12 g/dL , ferritin ≤100 or ≤300 ng/mL with transferrin saturation ≤30 % were r and omized to receive single ( n = 366 ) or weekly ( n = 343 ) FCM or SMC ( n = 360 and n = 366 ) . Results . Significantly greater ( P ≤ 0.001 ) increases in hemoglobin and iron indices occurred in FCM groups versus SMC . In the multidose study , up to two infusions of FCM were needed to reach target iron levels versus 3–5 of intravenous iron comparators . FCM and SMC groups had similar incidences and types of adverse events and serious adverse events . Transient hypophosphatemia not associated with adverse events or clinical sequelae occurred in the FCM groups . Conclusion . Intravenous FCM is safe , well tolerated , and associated with improvements in hemoglobin and iron indices comparable to SMC when administered in single doses of up to 750 mg at a rate of 100 mg/min . Fewer FCM infusions were required to reach target iron levels compared to other intravenous iron preparations This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks ( Q3W ) at fixed doses of 300 or 500 μg with or without intravenous ( IV ) iron in treating anemia in patients receiving multicycle chemotherapy . This Phase 2 , double‐blind , 2 × 2 factorial study r and omized patients to one of four treatment arms ; darbepoetin alfa 300 μg  ( n = 62 ) , darbepoetin alfa 300 μg plus IV iron ( n = 60 ) , darbepoetin alfa 500 μg ( n = 60 ) , or darbepoetin alfa 500 μg plus IV iron ( n = 60 ) . Patients had nonmyeloid malignancies , hemoglobin levels ≤10 g dL−1 , and no iron deficiency . Primary endpoint was achievement of target hemoglobin ( ≥11 g dL−1 ) . Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue ( FACT‐F ) score from baseline to end of study . Safety was evaluated by incidence of adverse events . No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed , therefore , results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups . Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin ( 75 and 78 % , respectively ) ; Kaplan – Meier median time to target hemoglobin was 10 and 8 weeks , respectively . More patients receiving IV iron ( 82 % ) than not receiving IV iron ( 72 % ) achieved hemoglobin target . Adverse events profiles were similar for darbepoetin alfa treatment groups . Transient anaphylactoid reactions were reported in two patients receiving IV iron . Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit , while added IV iron  improved treatment response in these patients . Am . J. Hematol . , 2010 . © 2010 Wiley‐Liss , OBJECTIVES : In the largest head-to-head comparison between an oral and an intravenous ( IV ) iron compound in patients with inflammatory bowel disease ( IBD ) so far , we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia ( IDA ) . METHODS : This prospect i ve , r and omized , comparative , open-label , non-inferiority study was conducted at 36 sites in Europe and India . Patients with known intolerance to oral iron were excluded . A total of 338 IBD patients in clinical remission or with mild disease , a hemoglobin ( Hb ) < 12 g/dl , and a transferrin saturation ( TSAT ) < 20 % were r and omized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula ( 225 patients ) or oral iron sulfate 200 mg daily ( equivalent to 200 mg elemental iron ; 113 patients ) . An interactive web response system method was used to r and omize the eligible patient to the treatment groups . The primary end point was change in Hb from baseline to week 8 . Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of −0.5 g/dl . The secondary end points , which tested for superiority , included change in Hb from baseline to weeks 2 and 4 , change in s-ferritin , and TSAT to week 8 , number of patients who discontinued study because of lack of response or intolerance of investigational drugs , change in total quality of life ( QoL ) score to weeks 4 and 8 , and safety . Exploratory analyses included a responder analysis ( proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks ) , the effect of regional differences and total iron dose level , and other potential predictors of the treatment response . RESULTS : Non-inferiority in change of Hb to week 8 could not be demonstrated . There was a trend for oral iron sulfate being more effective in increasing Hb  than iron isomaltoside 1,000 . The estimated treatment effect was −0.37 ( 95 % confidence interval ( CI ) : −0.80 , 0.06 ) with P=0.09 in the full analysis set ( N=327 ) and −0.45 ( 95 % CI : −0.88 , −0.03 ) with P=0.04 in the per protocol analysis set ( N=299 ) . In patients treated with IV iron isomaltoside 1,000 , the mean change in s-ferritin concentration was higher with an estimated treatment effect of 48.7 ( 95 % CI : 18.6 , 78.8 ) with P=0.002 , whereas the mean change in TSAT was lower with an estimated treatment effect of −4.4 ( 95 % CI : −7.4 , −1.4 ) with P=0.005 , compared with patients treated with oral iron . No differences in changes of QoL were observed . The safety profile was similar between the groups . The proportion of responders with Hb ≥2 g/dl ( IV group : 67 % ; oral group : 61 % ) were comparable between the groups ( P=0.32 ) . Iron isomaltoside 1,000 was more efficacious with higher cumulative doses of > 1,000 mg IV . Significant predictors of Hb response to IV iron treatment were baseline Hb and C-reactive protein ( CRP ) . CONCLUSIONS : We could not demonstrate non-inferiority of IV iron isomaltoside 1,000 compared with oral iron in this study . Based on the dose – response relationship observed with the IV iron compound , we suggest that the true iron dem and of IV iron was underestimated by the Ganzoni formula in our study . Alternative calculations including Hb and CRP should be explored to gauge iron stores in patients with IBD Background : The aim of this study was to compare the efficacy , safety and achievement of the target hemoglobin level ( Hb ≥10 g/dl ) in patients with preoperative anemia due to menorrhagia who received intravenous iron sucrose compared with oral iron protein succinylate for anemia management . Methods : Seventy-six patients with Hb levels < 9.0 g/dl who were scheduled to undergo surgical treatment were r and omized to receive either intravenous iron sucrose ( based on the calculated total iron deficit divided into 2 ampoule infusions intravenously 3 times a week , beginning 3 weeks before surgery ) or oral iron ( 80 mg/day of oral iron protein succinylate daily ) . Results : The intravenous iron group had higher increases in Hb ( 3.0 vs. 0.8 g/dl ; p < 0.0001 ) and ferritin levels ( 170.1 vs. 4.1 μg/l ; p < 0.0001 ) than the oral iron group . Achieving the target Hb was also higher in the intravenous iron group than in the oral iron group ( 76.7 vs. 11.5 % ; p < 0.0001 ) . There were tolerable adverse events in both groups . Conclusion : Preoperative intravenous iron sucrose administration is more effective  than oral iron and is as safe as oral iron therapy in the correction of preoperative anemia due to menorrhagia PURPOSE The concomitant use of intravenous ( IV ) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial . This study was design ed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local st and ard practice ( oral iron or no iron ) . PATIENTS AND METHODS In this multicenter , r and omized , open-label , phase III study , 396 patients with nonmyeloid malignancies and hemoglobin ( Hb ) less than 11 g/dL received darbepoetin alpha 500 microg with ( n = 200 ) or without ( n = 196 ) IV iron once every 3 weeks ( Q3W ) for 16 weeks . RESULTS The hematopoietic response rate ( proportion of patients achieving Hb > or= 12 g/dL or Hb increase of > or= 2 g/dL from baseline ) was significantly higher in the IV iron group : 86 % versus 73 % in the st and ard practice group ( difference of 13 % [ 95 % CI , 3 % to 23 % ] ; P = .011 ) . Fewer RBC transfusions ( week 5 to the end of the treatment period ) occurred in the IV iron group : 9 % versus 20 % in the st and ard practice group ( difference of -11 % [ 95 % CI , -18 % to -3 % ] ; P = .005 ) . Both treatments were well tolerated with no notable differences in adverse events . Serious adverse events related to iron occurred in 3 % of patients in the IV iron group and were mostly gastrointestinal in nature . CONCLUSION Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated , result ing in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone Iron stores assuring optimal efficacy/safety for erythropoiesis are unknown in the dialysis population . Using multicenter trial data , we related safety profiles , erythropoiesis-stimulating agent ( ESA ) , and intravenous iron dosing to achieved iron stores in 441 subjects r and omized 2 : 1 to ferric citrate or active control as their phosphate binder over 52 weeks .  Intravenous iron was given at each site 's discretion if ferritin ≤ 1,000 ng/mL and transferrin saturation ≤ 30 % . Multivariable time-dependent Cox regression jointly related the primary safety outcome ( composite of cardiac , infection , gastrointestinal , and hepatobiliary serious adverse events ) to moving averages of ferritin and transferrin saturation over the preceding 90 days with covariate adjustment . Multivariable generalized estimating equations related elevated ESA and intravenous iron doses to trailing 90-day averages of ferritin and transferrin saturation with covariate adjustment . The adjusted hazard ratio for the safety composite per 10 % increase in transferrin saturation was 0.84 ( 95 % confidence interval 0.68 - 1.02 , p = 0.08 ) and 1.09 ( 0.86 - 1.35 , p = 0.48 ) per 400 ng/mL increase in ferritin . The adjusted hazard ratio for the safety composite was 0.50 ( 0.29 - 0.88 , p = 0.016 ) for the highest transferrin saturation tertile vs. the lowest . Adjusted odds ratios for higher intravenous iron dose were lower in the highest ( 0.23 [ 0.16 - 0.35 ] , p < 0.001 ) and middle transferrin saturation tertile ( 0.42 [ 0.31 - 0.57 ] , p < 0.001 ) vs. lowest . Incidence of elevated ESA dose was lower in the highest transferrin saturation tertile ( p = 0.01 ) . Ferritin did not predict clinical events or ESA dose . Transferrin saturation may be a better marker than serum ferritin to judge optimal iron stores in dialysis patients . Transferrin saturations > 34 % are safe and provide maximal efficacy . BACKGROUND This trial evaluated the efficacy and safety of intravenous ( IV ) iron isomaltoside ( Monofer ) in comparison with placebo in first-time female blood donors . STUDY DESIGN AND METHODS The trial was a prospect i ve , double blind , placebo-controlled , r and omized , comparative , single-center trial of 85 first-time female blood donors . The subjects were r and omly assigned 1:1 to either 1000 mg IV iron isomaltoside infusion or placebo . The primary endpoint of the trial was change in hemoglobin ( Hb ) from baseline to right before the third blood donation . RESULTS The increase in Hb was significantly higher for iron isomaltoside compared with placebo right before both the second blood donation ( p = 0.0327 ) and the third blood donation ( primary endpoint , p < 0.0001 ) . Improvements in other iron-related variables ( plasma iron , plasma ferritin , transferrin saturation , and reticulocyte count ) in favor of iron isomaltoside were also observed . The trial was not powered on patient-reported outcomes . However , improvements in iron stores and Hb levels after iron isomaltoside administration were supported by the fact that several of the fatigue symptoms scores showed numerical differences in favor of iron isomaltoside . There were no differences in side effects between the groups . CONCLUSION In iron-deficient female blood donors a single IV iron isomaltoside administration result ed in an improvement in Hb concentration and iron stores and demonstrated a favorable safety profile comparable to placebo BACKGROUND Iron deficiency anaemia is the most common deficiency disorder in the world , affecting more than one billion people , with pregnant women at particular risk . OBJECTIVES AND DESIGN We conducted a single site , prospect i ve , nonblinded r and omized-controlled trial to compare the efficacy , safety , tolerability and compliance of st and ard oral daily iron versus intravenous iron . SUBJECTS We prospect ively screened 2654 pregnant women between March 2007 and January 2009 with a full blood count and iron studies , of which 461 ( 18 % ) had moderate IDA . Two hundred women matched for haemoglobin concentration and serum ferritin level were recruited . INTERVENTIONS Patients were r and omized to daily oral ferrous sulphate 250 mg ( elemental iron 80 mg ) with or without a single intravenous iron polymaltose infusion . RESULTS Prior to delivery , the intravenous plus oral iron arm was superior to the oral iron only arm as measured by the increase in haemoglobin level ( mean of 19.5 g/L vs. 12 g/L ; P < 0.001 ) ; the increase in mean serum ferritin level ( 222 microg/L vs. 18 ug/L ; P < 0.001 ) ; and the percentage of mothers with ferritin levels below 30 microg/L ( 4.5 % vs. 79 % ; P < 0.001 ) . A single dose of intravenous iron polymaltose was well tolerated without significant side effects . CONCLUSIONS Our data indicate that intravenous iron polymaltose is safe and leads to improved efficacy and iron stores compared to oral iron alone in pregnancy-related IDA OBJECTIVE This study was undertaken to determine the efficacy and safety of intravenously administered iron sucrose with versus without adjuvant recombinant human erythropoietin in the treatment of gestational iron-deficiency anemia resistant to therapy with orally administered iron alone . STUDY DESIGN Forty patients with gestational iron-deficiency anemia were r and omly assigned to receive intravenously iron sucrose plus recombinant human erythropoietin or iron sucrose alone twice weekly . Target hemoglobin value was 11.0 g/dL. Efficacy measures were reticulocyte count , increase in hematocrit , and time to target hemoglobin level ( treatment duration in weeks and need for continued therapy after 4 weeks ) . RESULTS Both regimens were effective , but with adjuvant recombinant human erythropoietin the reticulocyte counts were higher from day 4 ( P<.01 ) , increases in hematocrit were greater from day 11 ( P < .01 ) , and the median duration of therapy was shorter ( 18 vs 25 days ) , with more patients reaching the target hemoglobin level by 4 weeks of treatment ( n = 19 vs. n = 15 ) . The groups did not differ with respect to maternal-fetal safety parameters . CONCLUSION Adjuvant recombinant human erythropoietin safely enhanced the efficacy of iron sucrose in the treatment of gestational iron-deficiency anemia resistant to orally administered iron alone Study Objective A safe alternative to erythropoiesis‐stimulating agents to treat anemia is warranted in patients with cancer and anemia ; thus the objective of this trial was to compare the efficacy and safety of intravenous ( IV ) iron isomaltoside with oral iron in patients with cancer and anemia by testing the noninferiority of IV versus oral iron . Design Phase III , prospect i ve , open‐label , comparative , r and omized , noninferiority , multicenter trial . Setting Forty‐seven hospitals or private cancer clinics in Asia , the United States , and Europe . Patients A total of 350 patients with cancer and anemia . Intervention Patients were r and omized in a 2:1 ratio to either intravenous iron isomaltoside or oral iron sulfate . Patients in the iron isomaltoside group were then r and omized into an infusion subgroup ( single intravenous infusions of a maximum dose of 1000 mg over 15 min ) or a bolus injection subgroup ( bolus injections of 500 mg over 2 min ) . Measurements and Main Results The primary efficacy outcome was change in hemoglobin concentration from baseline to week 4 . Changes in other relevant hematology variables , effect on quality of life , and safety outcomes were also assessed . The primary efficacy outcome was tested for noninferiority , whereas the remaining outcomes were tested for superiority . Iron isomaltoside was noninferior to oral iron in change in hemoglobin concentration from baseline to week 4 ( difference estimate 0.016 , 95 % confidence interval –0.26 to 0.29 , p<0.001 ) . A faster onset of the hemoglobin response was observed with infusion of iron isomaltoside ( superiority test : p=0.03 at week 1 ) , and a sustained effect on hemoglobin level was shown in both the iron isomaltoside and oral iron treatment groups until week 24 . A significant mean decrease in fatigue score was observed from baseline to week 12 in the iron isomaltoside group ( p<0.001 ) but not in the oral iron group ( p=0.057 ) . A higher proportion of patients treated with oral iron  experienced adverse drug reactions ( 18.8 % vs 6.6 % , p<0.001 ) and discontinued the trial due to intolerance ( 8.0 % vs 0.9 % , p=0.001 ) . Transient hypophosphatemia ( phosphate level less than 2 mg/dl ) was reported at similar low frequencies among the groups : 7.1 % in the iron isomaltoside infusion subgroup versus 8.5 % in the iron isomaltoside bolus injection subgroup versus 5.4 % in the oral iron group . Conclusion This trial demonstrated comparable sustained increases in hemoglobin concentration over time with both iron isomaltoside and oral iron . Iron isomaltoside was better tolerated than oral iron , and fatigue was significantly decreased with iron isomaltoside . Low rates of clinical ly insignificant hypophosphatemia were reported in patients receiving both treatments There is limited safety information about ferric carboxymaltose ( FCM ) , a new intravenous iron preparation . This r and omized , crossover study compared the safety and tolerability of double‐blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia . Subjects ( 559 ) with iron deficiency anemia received a dose of either FCM ( 15 mg/kg , maximum 1000 mg ) over 15 minutes or placebo on day 0 . On day 7 , subjects received the other agent . Safety evaluations were performed on days 7 and 14 . The primary endpoint was the incidence of treatment‐emergent adverse events during each 7‐day study period . During the first 24 hours and during the 7‐day treatment period , at least one treatment‐emergent adverse event was experienced by 15.0 % and 29.3 % of subjects after FCM and 11.4 % and 19.7 % after placebo , respectively . Most were classified as Grade 1 or 2 . Six subjects had Grade 3 treatment‐emergent adverse events  after FCM and 9 subjects after placebo . One subject had a Grade 4 , and 1 subject had a Grade 5 treatment‐emergent adverse event , but neither was considered study drug‐related . During the first 24 hours of the treatment period , drug‐related adverse events were reported in 9.3 % of subjects receiving FCM and 4.8 % receiving placebo . Of drug‐related Grade 3 events , 4 subjects received FCM and 5 subjects received placebo . Administration of FCM ( 15 mg/kg , maximum of 1000 mg ) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia BACKGROUND Currently available intravenous ( IV ) iron agents vary in indication , dosing regimens and safety profiles . Ferric carboxymaltose ( FCM ) is a stable , non-dextran-containing iron formulation developed for rapid IV administration in high doses with controlled delivery of iron into target tissues . The objective of the present study was to evaluate the safety of FCM compared with st and ard medical care ( SMC ) in dialysis ( HD ) and non-dialysis-dependent ( NDD ) chronic kidney disease ( CKD ) patients . METHODS Adults 18 - 85 years of age with CKD were enrolled . NDD-CKD ( n = 204 ) patients received an undiluted IV dose of FCM ( 15 mg/kg to a maximum of 1000 mg IV ) and HD-CKD ( n = 50 ) patients received an undiluted IV push of 200 mg ~30 - 60 min into the dialysis session . Subjects r and omized to the SMC group ( n = 259 ) received treatment determined by the investigator that could include oral iron , IV iron or no iron . RESULTS Single doses of FCM of 200 mg in HD-CKD patients and up to 1000 mg in NDD-CKD patients were well tolerated . Incidences of treatment-emergent adverse events were similar between the groups : 30.3 % ( 77 of 254 ) in the FCM group and 32.8 % ( 85 of 259 ) in the SMC group . Incidences of serious adverse events were higher in the SMC group overall and in patients receiving iron sucrose or sodium ferric gluconate . There were no clinical ly significant differences in laboratory or clinical chemistry values or vital signs between the groups . There were no statistically significant differences between the FCM and SMC groups in indices of hemoglobin ( Hb ) improvement , including proportions of patients achieving a ≥ 1 g/dL increase in Hb and proportions of patients achieving Hb level of > 12 g/dL. CONCLUSION FCM in doses of 200 mg for HD-CKD patients and up to 1000 mg in NDD-CKD patients were well tolerated and displayed comparable efficacy to other IV iron formulations Iron deficiency anemia ( IDA ) is the most common form of anemia worldwide . Although oral iron is used as first‐line treatment , many patients are unresponsive to or can not take oral iron . This Phase III , open‐label , non‐inferiority study compared the efficacy and safety of ferumoxytol , a rapid , injectable intravenous ( IV ) iron product with low immunological reactivity and minimal detectable free iron , with IV iron sucrose in adults with IDA of any cause . Patients ( N = 605 ) were r and omized 2:1 to receive ferumoxytol ( n = 406 , two doses of 510 mg 5 ± 3 days apart ) or iron sucrose ( n = 199 , five doses of 200 mg on five nonconsecutive days over 14 days ) and followed for 5 weeks . Ferumoxytol demonstrated noninferiority to iron sucrose at the primary endpoint , the proportion of patients achieving a hemoglobin increase of ≥2 g dL−1 at any time from Baseline to Week 5 ( ferumoxytol , 84.0 % [ n = 406 ] vs. iron sucrose , 81.4 % [ n = 199 ] ) , with a noninferiority margin of 15 % . Ferumoxytol was superior to iron sucrose ( 2.7 g dL−1 vs. 2.4 g dL−1 ) in the mean change in hemoglobin from Baseline to Week 5 ( the alternative preplanned primary endpoint ) with P = 0.0124 . Transferrin saturation , quality ‐of‐life measures , and safety outcomes were similar between the two treatment groups . Overall , ferumoxytol  demonstrated comparable safety and efficacy to iron sucrose , suggesting that ferumoxytol may be a useful treatment option for patients with IDA in whom oral iron was unsatisfactory or could not be used . Am . J. Hematol . 89:646–650 , 2014 . © 2014 Wiley Periodicals , Although oral iron is the initial treatment approach for iron deficiency anemia ( IDA ) , some patients fail to respond to or can not tolerate oral iron . This double‐blind safety and efficacy study of the intravenous ( IV ) iron , ferumoxytol , r and omized patients with a history of unsatisfactory oral iron therapy , or in whom oral iron could not be used ,  to ferumoxytol ( n = 609 ) or placebo ( n = 203 ) . The proportion of patients achieving the primary endpoint ( hemoglobin increase ≥2.0 g/dL at Week 5 ) was 81.1 % with ferumoxytol versus 5.5 % with placebo ( P < 0.0001 ) . The mean increase in hemoglobin from Baseline to Week 5 , a secondary endpoint ( also the alternative preplanned primary efficacy endpoint for other health authorities ) , was 2.7 versus 0.1 g/dL ( P < 0.0001 ) . Achievement of a hemoglobin ≥12 g/dL , time to a hemoglobin increase ≥2.0 g/dL , and improvement in the Functional Assessment of Chronic Illness Therapy Fatigue score also significantly favored ferumoxytol over placebo at Week 5 (  P < 0.0001 ) . Ferumoxytol treatment‐emergent adverse events were mainly mild to moderate . Ferumoxytol was effective and well tolerated in patients with IDA of any underlying cause in whom oral iron was ineffective or could not be used . This trial was registered at www . clinical trials.gov as # NCT01114139 . Am . J. Hematol . 89:7–12 , 2014 . © 2013 Wiley Periodicals , OBJECTIVE Intravenous ( IV ) iron has been used as a treatment to reduce Restless Legs Syndrome ( RLS ) symptoms , but two double-blinded trials of a frequently prescribed IV iron formulation , iron sucrose , failed to show lasting efficacy . This study evaluates efficacy and safety of a new IV iron formulation ( ferric carboxymaltose , FCM ) with molecular properties that may make iron more available for uptake to the brain than iron sucrose does . METHODS In this 28-day , multi-centre , r and omised , placebo-controlled trial 46 RLS patients were discontinued from all RLS treatment . Twenty-four received 500 mg FCM in two doses 5 days apart and 22 received a matching placebo . At day 28 , those on placebo were given a single 1000 mg IV FCM and those not responding to initial treatment were given a third dose of 500 mg FCM . Patients were followed up for 24 weeks or until needing added RLS treatment . RESULTS FCM significantly improved primary and secondary outcomes compared to placebo :  International Restless Legs Syndrome study group severity scale ( IRLS ) average ( SD ) decrease of 8.9 ( 8.52 ) versus 4.0 ( 6.11 ) , p=0.040 ; Clinical Global Inventory of Change ( CGI-1 ) very much or much improved 48.3 % versus 14.3 % , p=0.004 . Quality of life was also significantly improved . Of the 24 with initial iron treatment 45 % responded and 29 % remitted ( IRLS ≤ 10 ) at day 28 , and 25 % continued free of other RLS medications at 24 weeks after treatment . The single 1000 mg dose on day 28 produced the same degree of treatment response as the divided dose , but the added 500 mg dose for those not responding to the initial treatment showed little benefit . There were no significant adverse events . CONCLUSIONS IV FCM  provided a safe and effective treatment for RLS that lasted for at least 24 weeks for some patients . Larger studies are needed to confirm these results OBJECTIVES 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 . METHODS 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 r and omized to either ferric carboxymaltose ( FCM , 500 - 1000 mg as single shot infusion over 20 min ) or ferric gluconate ( FG , 62.5 mg once weekly ) . RESULTS 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 ( clinical ly and with respect to laboratory data ) in lipoprotein apheresis patients , however FCM led to a more rapid and steeper rise of iron parameters . CONCLUSIONS 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 . H and led 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 For nearly half a century , parenteral iron has been considered dangerous and for use only in extreme situations and when oral iron was not tolerated . This proscription was based largely on poorly characterised and infrequent anaphylactoid reactions to the high-molecular-weight dextran preparation ( Imferon ) that for most of this time was the only product available . Moreover , when parenteral iron was necessary , the recommended approach was small intramuscular doses ( ≤100 mg ) , even after intravenous administration of the total iron defi cit as a single dose or as repetitive boluses was shown to be as safe and eff ective as the intramuscular route . This mindset persists despite the subsequent introduction of low-molecular-weight iron dextran and two iron salt preparations , ferric gluconate and iron saccharate ( the latter is also known as iron sucrose ) , all of which are associated with fewer serious adverse events than the high-molecular-weight dextran . The introduction of recombinant erythropoietin for dialysis patients was associated with the development , in some individuals , of functional iron defi ciency that limited effi cacy . Intravenous iron , unlike oral iron , improves erythropoietic response in dialysis patients , and is now routinely used . The discovery of the iron regulatory peptide , hepcidin , has improved our underst and ing of the anaemia of chronic infl ammatory states , including cancer . Hepcidin is upregulated in these conditions , result ing in increased synthesis by the liver . Hepcidin inhibits iron transport across cell membranes , which decreases the accessibility of storage iron and gastrointestinal absorption of dietary iron , leading to an increased frequency of iron-restricted erythropoiesis , especially during therapy with recombinant erythropoietin . The most frequent laboratory fi ndings during the anaemia of chronic infl ammation are hypoferraemia and a low percent transferrin saturation , although these fi ndings are not always present . The increasing use of recombinant erythropoietin to treat anaemia in patients with chronic diseases has exp and ed the population of patients with functional iron defi ciency and increased interest in safe rational approaches to parenteral iron therapy . There is mounting evidence that anaemic patients with cancer undergoing chemotherapy and receiving  recombinant erythropoietin respond better when parenteral iron is administered . This benefi t is independent of baseline iron variables , such as ferritin , low percentage transferrin saturation , and stainable marrow haemosiderin , leaving the clinician in need of laboratory variables to reliably detect iron-restricted erythropoiesis in patients with infl ammatory illnesses and to predict improvement of erythropoietic response to parenteral iron in the setting of infl ammatory illness . Two new laboratory measures look promising : percent hypochromic red blood cells and reticulocyte haemoglobin content . These tests are reliable and accurate correlates of functional iron defi ciency . Although these investigations are not yet widely available , their use will probably exp and and guide identifi cation of functional iron defi ciency and rational intervention with parenteral iron . Currently , four parenteral iron preparations are available ( table ) . No r and omised trials have compared the safety and effi cacy of any of these agents . The largest retrospective review of dialysis experience suggests that most serious adverse events have been associated with the high-molecular-weight iron dextrans ( Imferon , which is no longer available and the current preparation , Dexferrum ) and are rare ( < 1:200 000 ) with the low-molecular-weight iron dextran or the two iron salts ( fi gure ) . Adverse event rates might be somewhat higher in patients with infl ammatory diseases in which immune-mediated drug reactions  may be observed more commonly than in dialysis patients . Some of the adverse clinical experience with parenteral iron is due to inappropriate supportive care . Myalgias , when they include chest and back discomfort , are mistakenly described as anaphylaxis , prompting Low – molecular – weight iron dextran Iron saccharate Ferric gluconate High – molecular – weight iron Objective To explore the safety and efficacy of intravenous ( IV ) iron sucrose in maintenance peritoneal dialysis ( PD ) . Design R and omized , controlled , parallel-group single-center trial . Setting Blood Purification Center of Chaoyang , Beijing Capital University of Medical Science , China . Methods 46 patients on PD were involved in this trial . 26 patients received IV iron sucrose ( 200 mg iron ) once per week for 4 weeks then once every other week for a further 4 weeks . The other 20 patients received oral ferrous succinate , 200 mg three times per day , for 8 weeks . Hemoglobin , hematocrit , serum ferritin ( SF ) level , and transferrin saturation ( TSAT ) were assessed at baseline and then again after 2 , 4 , and 8 weeks of treatment . Results There were no differences between the IV and oral groups in terms of sex , age , duration of PD , mean dialysate dosage per day , erythropoietin dosage per week , or hematological parameters at baseline . After 4 and 8 weeks of treatment , mean Hb and Hct were significantly increased in the IV group and were also significantly higher than those in the oral group . Levels of SF and TSAT were also significantly increased in the IV group , and significantly higher than in the oral group . After 8 weeks , the response rate in the IV group was 94.8 % , which was significantly higher than that in the oral group . The mean erythropoietin dose was significantly lower in the IV group than in the oral group . Hb , Hct , SF , and TSAT levels were maintained between 4 and 8 weeks in the IV group despite the decrease in dose frequency . There were no adverse events with IV iron . Eight patients in the oral group had adverse gastrointestinal effects . Conclusion IV iron sucrose is safe in PD patients . It increases Hb levels and serum iron parameters more effectively than oral iron ; it is well tolerated and can permit reductions in the required dose of erythropoietin Abstract Objective . Iron isomaltoside 1000 ( Monofer ® ) is a high-dose intravenous ( IV ) iron , which in a recent 8 weeks trial in inflammatory bowel disease ( IBD ) subjects with iron deficiency anemia ( IDA ) demonstrated good tolerability and efficacy . The present trial is an extension to this trial , which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin ( Hb ) ≥12.0 g/dl . Material and methods . This was a prospect i ve , open-label , 12 months trial of European IBD subjects willing to participate after completing the lead-in trial . Subjects were allowed re-dosing with 500–2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm . Outcome measures included Hb , safety parameters and need for additional iron dosing . Results . A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g ( mean cumulative dose 2.2 g ) . The mean ( SD ) Hb was 12.3 ( 1.5 ) g/dl at baseline , 12.8 ( 1.6 ) g/dl at 3 months , 12.8 ( 1.6 ) g/dl at 6 months , 12.9 ( 1.4 ) g/dl at 9 months and 12.9 ( 1.6 ) g/dl at 12 months . Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months . Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects , who recovered without sequelae . Conclusion . Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues . Trial registration : Clinical Trial.gov identifier : NCT01410435 BACKGROUND AND OBJECTIVES Intravenous iron is a key component of anemia management for chronic kidney disease ( CKD ) .  Ferumoxytol is a unique intravenous iron product that can be administered as a rapid injection in doses up to 510 mg . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a r and omized , open-label , controlled , multicenter Phase 3 trial to evaluate the safety and efficacy of intravenous ferumoxytol compared with oral iron .  Anemic patients with CKD stage 5D on hemodialysis and on a stable erythropoiesis-stimulating agent regimen received either two injections of 510 mg of ferumoxytol within 7 d ( n = 114 ) or 200 mg elemental oral iron daily for 21 d ( n = 116 ) . The primary efficacy endpoint was the change in hemoglobin from baseline to day 35 . Safety was closely monitored . RESULTS Ferumoxytol result ed in a mean increase in hemoglobin of 1.02 + /- 1.13 g/dl at day 35 compared with 0.46 + /- 1.06 g/dl with oral iron ( P = 0.0002 ) . Twice as many ferumoxytol-treated patients than oral iron-treated patients achieved a > or = 1 g/dl hemoglobin increase at day 35 ( P = 0.0002 ) . There was a greater mean increase in transferrin saturation ( TSAT ) with ferumoxytol compared with oral iron at day 35 ( P < 0.0001 ) . The larger hemoglobin increase after ferumoxytol compared with oral iron at day 35 persisted after adjustment for baseline hemoglobin , TSAT , and serum ferritin . Overall adverse event rates were comparable between groups . CONCLUSIONS In patients on hemodialysis , rapid intravenous injection of 510 mg of ferumoxytol led to significantly greater hemoglobin increases compared with oral iron , with comparable tolerability OBJECTIVES To compare the safety and efficacy of iron carboxymaltose with ferrous sulfate to treat iron deficiency anemia in the post partum . METHODS Patients were r and omized ( 2:1 ratio ) to receive iron carboxymaltose  ( up to 3 weekly doses of 1000 mg maximum , applied in 15 min ; n=227 ) or ferrous sulfate ( 100 mg twice daily , 12 weeks ; n=117 ) . Changes in hemoglobin and iron stores up to week 12 were analyzed . RESULTS Iron carboxymaltose was as effective as oral iron sulfate in changing hemoglobin , despite the much shorter treatment period ( 2 weeks vs 12 weeks ) . Ferritin levels were significantly higher . Except for injection site burning , iron carboxymaltose was better tolerated than ferrous sulfate , mainly concerning gastrointestinal side effects . There were no safety concerns identified in breast-fed infants . CONCLUSION Parenteral iron carboxymaltose is a safe and effective treatment option for postpartum anemia , with advantages of a shorter treatment period , better compliance , rapid normalization of iron storages , and lower incidence of gastrointestinal side effects
There was no increased risk of infections with IV iron .
Gastrointestinal AEs were reduced with IV iron .
CONCLUSION Intravenous iron therapy is not associated with an increased risk of SAEs or infections .
Infusion reactions are more pronounced with IV iron
OBJECTIVE To amass all available evidence regarding the safety of intravenous ( IV ) iron preparations to provide a true balance of efficacy and safety .