Safety and Efficacy of Intravenous Ferric Carboxymaltose (750 mg) in the Treatment of Iron Deficiency Anemia: Two Randomized, Controlled Trials Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations. A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients Direct Comparison of the Safety and Efficacy of Ferric Carboxymaltose versus Iron Dextran in Patients with Iron Deficiency Anemia A Novel Intravenous Iron Formulation for Treatment of Anemia in Inflammatory Bowel Disease: The Ferric Carboxymaltose (FERINJECT®) Randomized Controlled Trial Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. High-dose intravenous treatment in iron deficiency anaemia in inflammatory bowel disease: early efficacy and impact on quality of life. A Blinded, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Ferric Carboxymaltose in Iron-Deficient Patients with Fibromyalgia FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. 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. TREATMENT OF ANEMIA AND IMPROVEMENT OF QUALITY OF LIFE AMONG PATIENTS WITH CROHN'S DISEASE: experience using ferric carboxymaltose. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women – PREFER a Randomized, Placebo-Controlled Study Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia. Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients with chronic heart failure in Sweden Ferric carboxymaltose in patients with heart failure and iron deficiency. Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia Better Tolerance of Iron Polymaltose Complex Compared with Ferrous Sulphate in the Treatment of Anaemia Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anemia in pregnant women. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. The effect of intravenous ferric carboxymaltose on health-related quality of life in patients with chronic heart failure and iron deficiency: a subanalysis of the FAIR-HF study
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 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 Background . Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents ( ESAs ) in non-dialysis-dependent chronic kidney disease ( ND-CKD ) patients .  Current intravenous iron agents can not be administered in a single high dose because of adverse effects . Ferric carboxymaltose , a non-dextran parenteral iron preparation , can be rapidly administered in high doses . Methods . This open-label trial r and omized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m2 , haemoglobin ≤ 11 g/dL , transferrin saturation ≤ 25 % , ferritin ≤ 300 ng/mL , and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min ( with up to two additional doses of 500 mg at 2-week intervals ) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days . Results . In the modified intent-to-treat population , the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4 % with ferric carboxymaltose and 34.7 % with oral iron ( P < 0.001 ) . At Day 42 , mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL ( P = 0.005 ) , mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL ( P < 0.001 ) and mean increase in transferrin saturation was 13.6 ± 11.9 % vs 6.1 ± 8.1 % ( P < 0.001 ) . Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron ( 2.7 % and 26.2 % , respectively ; P < 0.0001 ) . Conclusions . We conclude that 1000 mg ferric carboxymaltose can be rapidly administered , is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients Several intravenous iron complexes are available for the treatment of iron deficiency anemia ( IDA ) .  Iron dextran ( DEX ) is associated with an elevated risk of potentially serious anaphylactic reactions , whereas others must be administered in several small infusions to avoid labile iron reactions . Ferric carboxymaltose ( FCM ) is a nondextran intravenous iron which can be administered in high single doses . A r and omized , open label , and multicenter comparison of FCM to DEX in adults with IDA and baseline hemoglobin of ≤11.0 g/dL was conducted . A total of 160 patients were in the safety population  ( FCM n = 82 ; DEX n = 78 ) . Adverse events , including immune system disorders ( 0 % in FCM versus 10.3 % in DEX , P = 0.003 ) and skin disorders ( 7.3 % in FCM versus 24.4 % in DEX , P = 0.004 ) , were less frequently observed in the FCM group . A greater portion of patients in the FCM group experienced a transient , asymptomatic decrease in phosphate compared to patients in the DEX group ( 8.5 % in FCM versus 0 % in DEX , P = 0.014 ) . In the FCM arm , the change in hemoglobin from baseline to the highest observed level was 2.8 g/dL , whereas the DEX arm displayed a change of 2.4 g/dL ( P = 0.20 ) . Treatment of IDA with FCM result ed in fewer hypersensitivity-related reactions  than DEX BACKGROUND AIMS : Anemia is a common complication of inflammatory bowel diseases ( IBD ) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation , ferric carboxymaltose ( FeCarb ) , in comparison with oral ferrous sulfate ( FeSulf ) in reducing iron deficiency anemia ( IDA ) in IBD . METHODS : Two hundred patients were r and omized in a 2:1 ratio ( 137 FeCarb:63 FeSulf ) to receive FeCarb ( maximum 1,000 mg iron per infusion ) at 1-wk intervals until the patients ' calculated total iron deficit was reached or FeSulf ( 100 mg b.i.d . ) for 12 wk . The primary end point was change in hemoglobin ( Hb ) from baseline to week 12 . RESULTS : The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group , demonstrating noninferiority ( P = 0.6967 ) . Response ( defined as Hb increase of > 2.0 g/dL ) was higher for FeCarb at week 2 ( P = 0.0051 ) and week 4 ( P = 0.0346 ) . Median ferritin increased from 5.0 to 323.5 μg/L at week 2 , followed by a continuous decrease in the FeCarb group ( 43.5 μg/L at week 12 ) . In the FeSulf group , a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed . Treatment-related adverse events ( AEs ) occurred in 28.5 % of the FeCarb and 22.2 % of the FeSulf groups , with discontinuation of study medication due to AEs in 1.5 % and 7.9 % , respectively . CONCLUSIONS : FeCarb is effective and safe in  IBD-associated anemia  . It is noninferior to FeSulf in terms of Hb change over 12 wk , and provides a fast Hb increase and a sufficient refill of iron stores BACKGROUND Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease ( NDD-CKD ) frequently requires parenteral iron replacement , but existing therapies often require multiple administrations . We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose ( FCM ) , a non-dextran parenteral iron permitting large single-dose infusions , versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD . METHODS A total of 2584 participants were r and omized to two doses of FCM 750 mg in one week , or iron sucrose 200 mg administered in up to five infusions in 14 days . The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56 . The primary composite safety endpoint included all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , unstable angina , congestive heart failure , arrhythmias and hyper- and hypotensive events . RESULTS The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group ( 95 % CI , 0.13 - 0.28 ) . Similar results were observed across all subgroups , except Stage 2 CKD . More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 ( 48.6 versus 41.0 % ; 95 % CI , 3.6 - 11.6 % ) . There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint , including the major adverse cardiac events of death , myocardial infa rct ion , or stroke . A significant difference in the number of protocol -defined , predominantly transient hypertensive episodes was observed in the FCM group . CONCLUSIONS Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia BACKGROUND Anaemia and iron deficiency are very common in inflammatory bowel disease . Clinical trials have shown intravenous iron to be effective and well tolerated . However , published experience in clinical practice with specific evaluation of the effect on quality of life is limited . MATERIAL AND METHODS We carried out a prospect i ve , multicentre , observational study on the effects of ferric carboxymaltose in the treatment of iron deficiency anaemia in inflammatory bowel disease . Anaemia and iron deficiency were defined according to World Health Organization criteria . Efficacy and safety were evaluated at infusion , at 2 weeks and at 12 weeks . Quality of life was evaluated according to the SIBDQ-9 index . Complete response was defined as anaemia correction or more tan 2 g/dL increase in haemoglobin . RESULTS A total of 88 courses of ferric carboxymaltose in 72 patients were evaluated . Complete response was observed in 46 % of patients at week 2 , and 81.2 % at week 12 . Quality of life improved significatively at week 2 in both complete responders and partial responders ( p<0.0005 ) ; complete responders showed siginficantly better response ( p=0.016 ) . No predictive factor was identified . Only one transient adverse effect was observed ; however , this was severe . DISCUSSION Ferric carboxymaltose showed comparable efficacy to that demonstrated in clinical trials . After only two weeks of treatment , there was a significant improvement in quality of life , with a greater effect observed in those patients with a complete haematologic response . Intravenous iron can very quickly improve quality of life in inflammatory bowel disease Introduction This study sought to compare efficacy and safety of ferric carboxymaltose vs. placebo in iron-deficient patients with fibromyalgia . Methods This blinded , placebo-controlled , phase 2 study r and omized adults with fibromyalgia and Revised Fibromyalgia Impact Question naire ( FIQR ) scores ≥ 60 , ferritin levels < 0.05 µg/ml , and transferrin saturation < 20 % ( 1:1 ) to receive ferric carboxymaltose [ 15 mg/kg ( up to 750 mg ) ] , or placebo ( 15 cc  normal saline ) intravenously on study days 0 and 5 . Patients visited the clinic on days 14 , 28 , and 42 for efficacy and safety assessment s. The primary efficacy endpoint was proportion of patients with a ≥ 13-point improvement from baseline to day 42 in FIQR scale score . Secondary endpoints included changes from baseline in FIQR scale , Brief Pain Inventory ( BPI ) total score , Medical Outcomes Study ( MOS ) Sleep scale , Fatigue Visual Numeric Scale ( VNS ) , iron indices ( transferrin saturation and ferritin ) , and safety . Results The efficacy analysis group comprised 80 patients , and the safety analysis group comprised 81 .  More ferric carboxymaltose patients ( 77 % ) vs. placebo patients ( 67 % ) achieved the primary endpoint , but the difference was not significant . Greater improvements from baseline to day 42 were observed for ferric carboxymaltose vs. placebo in FIQR total score , BPI total score , Fatigue VNS score , and iron indices . Mean changes in MOS Sleep scale scores were similar between groups . Ferric carboxymaltose was safe and well tolerated . Conclusions Compared with placebo , ferric carboxymaltose improved measures of fibromyalgia severity and was well tolerated . The current results suggest that ferric carboxymaltose shows benefit in iron-deficient patients with concurrent fibromyalgia . Funding Luitpold Pharmaceuticals , Inc . Trial Registration Clinical Trials.gov identifier , NCT02409459 BACKGROUND & AIMS Iron deficiency anemia ( IDA ) is common in chronic diseases and intravenous iron is an effective and recommended treatment . However , dose calculations and inconvenient administration may affect compliance and efficacy . We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen ( FCM ) with individually calculated iron sucrose ( IS ) doses in patients with inflammatory bowel disease ( IBD ) and IDA . METHODS This r and omized , controlled , open-label , multicenter study included 485 patients with IDA ( ferritin < 100 μg/L , hemoglobin [ Hb ] 7 - 12 g/dL [ female ] or 7 - 13 g/dL [ male ] ) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries . Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron , or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron . Primary end point was Hb response ( Hb increase ≥ 2 g/dL ) ; secondary end points included anemia resolution and iron status normalization by week 12 . RESULTS The results of 240  FCM-treated and 235 IS-treated patients were analyzed . More patients with FCM than IS achieved Hb response ( 150 [ 65.8 % ] vs 118 [ 53.6 % ] ; 12.2 % difference , P = .004 ) or Hb normalization ( 166 [ 72.8 % ] vs 136 [ 61.8 % ] ; 11.0 % difference , P = .015 ) . Both treatments improved quality of life scores by week 12 . Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience . Deviations from scheduled total iron dosages were more frequent in the IS group . CONCLUSIONS The simpler FCM-based dosing regimen showed better efficacy and compliance , as well as a good safety profile , compared with the Ganzoni-calculated IS dose regimen 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 OBJECTIVES Anemia is the most common hematological alteration in patients with Crohn 's disease , and is frequently related to intestinal inflammatory activity . Its cause is multifactorial and mostly associated with absolute iron deficiency ( iron deficiency anemia ) and /or functional iron deficiency ( inflammation anemia or anemia of chronic disease ) . It may also be identified through other causes , such as folic acid or vitamin B12 deficiency and secondary to adverse effects from medications ( salicylic derivatives and immunosuppressive drugs ) . In the present study , patients with active Crohn 's disease and anemia were evaluated and treated with intravenous ferric carboxymaltose . We discuss the therapeutic schemes ( doses ) , safety , results and improvement of quality of life . METHODS In the present prospect i ve study , 10 consecutive patients with Crohn 's disease , with moderate to severe activity , with anemia ( Hb : 6.7 to 10 g/dL ) , who were attended between March 2014 and March 2015 , were evaluated . Six ( 60 % ) were men and four were women , all with moderate or severe anemia ( hemoglobin < 10 g/dL ) . They were treated with a maximum of three intravenous infusions of 1000 mg of ferric carboxymaltose , of at least 15 minutes in duration . It was also sought to correlate the inflammatory Crohn 's disease activity degree ( measured using the Crohn 's Disease Activity Index , CDAI ) and C-reactive protein level with the severity of anemia . The primary outcome was an increase in Hb of ≥2 g/dL and the secondary outcome was the normalization of anemia ( Hb ≥12 g/dL for women and ≥13 g/dL for men ) and the improvement in quality of life seen 12 weeks after the last application of carboxymaltose . RESULTS Among the 10 patients studied , parenteral iron supplementation was administered in three cases during hospitalization and the others received this on an outpatient basis . The total iron dose ranged from 1,000 to 2,000 mg , with an average of 1,650 mg . Crohn 's disease activity measured using CDAI and C-reactive protein correlated with the intensity of anemia . An increase of 2 g/dL occurred in eight ( 80 % ) patients after 12 weeks and normalization of anemia was found in seven ( 70 % ) patients . Improvements in quality -of-life scores were found for all ( 100 % ) patients after 12 weeks . Carboxymaltose was well tolerated . Three patients presented adverse reactions ( two with nausea and one with headache ) of mild intensity . CONCLUSIONS Anemia is a frequent complication for Crohn 's disease patients . Intravenous iron therapy has been recommended for Crohn 's disease patients , because for these patients , oral iron absorption is very limited . This is because of the inflammatory state and " blocking " of iron entry into enterocytes through hepcidin action on ferroportin , along with the elevated rates of gastrointestinal adverse events that compromise adherence to treatment and possibly aggravate the intestinal inflammatory state . The degree of Crohn 's disease activity , as measured using CDAI and C-reactive protein , correlates with the severity of anemia .  Carboxymaltose is a safe drug , which can be administrated in high doses ( up to 1,000 mg per application per week ) and corrects anemia and iron stocks over a short period of time , with consequent improvement in quality of life BACKGROUND The objective was to evaluate efficacy and safety of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding . STUDY DESIGN AND METHODS In a r and omized , controlled trial , 477 women with anemia , iron deficiency , and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose ( < or=1000 mg over 15 min , repeated weekly to achieve a total calculated replacement dose ) or 325 mg of ferrous sulfate ( 65 mg elemental iron ) prescribed orally thrice daily for 6 weeks . RESULTS Compared to those assigned to ferrous sulfate , more patients assigned to ferric carboxymaltose responded with a hemoglobin ( Hb ) increase of 2.0 g/dL or more ( 82 % vs. 62 % , 95 % confidence interval for treatment difference 12.2 - 28.3 , p < 0.001 ) , more achieved a 3.0 g/dL or more increase ( 53 % vs. 36 % , p < 0.001 ) , and more achieved correction ( Hb > or= 12 g/dL ) of anemia ( 73 % vs. 50 % , p < 0.001 ) . Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue ( p < 0.05 ) . There were no serious adverse drug events . CONCLUSIONS In patients with iron deficiency anemia due to heavy uterine bleeding , rapid IV administration of large doses of a new iron agent , ferric carboxymaltose , is more effective than oral iron therapy in correcting anemia , replenishing iron stores , and improving quality of life Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin < 50 µg/L and transferrin saturation < 20 % , or ferritin < 15 µg/L ) and normal or borderline hemoglobin ( ≥115 g/L ) were enrolled in 21 sites in Austria , Germany , Sweden and Switzerl and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p<0.001 ) . At Day 56 , all FCM-treated patients had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin < 15 µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov 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 Abstract Background : Compromised iron status is important in restless legs syndrome pathophysiology . We compared the efficacy and tolerability of ferric carboxymaltose ( single intravenous dose ) versus placebo for restless legs syndrome treatment in iron‐deficient nonanemic patients . Methods : Patients with moderate to severe restless legs syndrome and serum ferritin < 75 μg/L ( or serum ferritin 75‐300 μg/L and transferrin saturation < 20 % ) were r and omized to ferric carboxymaltose ( 1000 mg iron ) or placebo . Mean change difference between ferric carboxymaltose and placebo in International Restless Legs Syndrome Severity Scale score from baseline to week 4 was the primary end point ; week 12 was a secondary end point . Results : Ferric carboxymaltose treatment ( n = 59 ) led to nonsignificant improvement over placebo ( n = 51 ) in International Restless Legs Syndrome Severity Scale score at week 4 ( difference [ 95 % confidence interval ] , ‐2.5 [ ‐5.93 to 1.02 ] , P = 0.163 ) , reaching significance by week 12 ( ‐4.66 [ ‐8.59 to ‐0.73 ] , P = 0.021 ) . Conclusions : In patients who responded to treatment , ferric carboxymaltose may require more time to stabilize restless legs syndrome than previously assumed . © 2017 The Authors . Movement Disorders published by Wiley Periodicals , Inc. on behalf of International Parkinson and Movement Disorder Society Abstract Objective : Iron deficiency is a common but treatable comorbidity in chronic heart failure ( CHF ) that is associated with impaired health-related quality -of-life ( HRQoL ) . This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose ( FCM ) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective . Methods : A cost-effectiveness analysis with a time horizon of 24 weeks was performed to compare FCM treatment with placebo . Data on health outcomes and medical re source use were mainly taken from the FAIR-HF trial and combined with Swedish cost data . An incremental cost-effectiveness ratio ( ICER ) was calculated as well as the change in per-patient costs for primary care and hospital care . Results : In the FCM group compared with placebo  , quality -adjusted life years ( QALYs ) are higher ( difference = 0.037 QALYs ) , but so are per-patient costs [ ( difference = SEK 2789 ( € 303 ) ] . Primary care and hospital care equally share the additional costs , but within hospitals there is a major shift of costs from inpatient care to outpatient care . The ICER is SEK 75,389 ( € 8194 ) per QALY . The robustness of the result is supported by sensitivity analyses . Conclusions : Treatment of iron deficiency in CHF with FCM compared with placebo is estimated to be cost-effective . The ICER in the base case scenario is twice as high as previously thought , but noticeably below SEK 500,000 ( € 54,300 ) per QALY , an informal average reference value used by the Swedish Dental and Pharmaceutical Benefits Agency . Increased HRQoL and fewer hospitalizations are the key drivers of this result BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) 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 ) 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 Absolute iron deficiency , irrespective of aetiology , remains a major and worldwide cause of morbidity . After correction of the causative lesion , reconstitution of haemoglobin level and body iron stores is traditionally achieved with oral administration of ferrous salts . The latter have significant gastrointestinal tract side-effects that , in the short-term , may impair compliance . With protracted administration these products can cause lipid peroxidation which , in turn , may accelerate atherogenesis . An alternative formulation is an iron polymaltose complex where animal data supported a promoting effect of glycerophosphate . Setting and Trial Design This was a single-centre , open , r and omised , multidose four treatment parallel group study . A st and ard dose of ferric polymaltose complex with two differing levels of glycerophosphate was compared with an equivalent amount of iron supplied as ferrous sulphate in anaemic volunteer blood donors . The endpoints were rate of haemoglobin rise and re-expansion of body iron stores reflected in blood ferritin concentration , as well as percentage saturation of transferrin . Secondary observations were changes in the proportion of hypochromic red cells during the course of treatment , erythropoietin levels and tolerability of the two formulations . Results Outcome in the rat model suggested that the utilisation of iron from polymaltose might be enhanced by glycerophosphate . However , in donors this difference was not evident and , accordingly , the data from the three polymaltose groups combined and compared to those receiving ferrous sulphate . The rate at which haemoglobin level improved , red cell indices returned to normal , and the number of hypochromic and microcytic red cells fell was not significantly different between the groups . Similarly the serum iron , percentage saturation of transferrin and red cell ferritin were comparable . In contrast the serum ferritin levels were higher for those receiving ferrous sulphate . Additionally , side-effects were significantly more frequently encountered with the latter preparation . Conclusion These data demonstrate that the addition of glycerophosphate , observed to be beneficial in rats , did not occur in humans . Secondly , in the blood donors , equivalent amounts of iron provided as the polymaltose , with or without glycerophosphate or ferrous sulphate , corrected haemoglobin concentration and morphologically abnormal erythropoiesis at comparable rates . Similarly iron stores are replenished to an equivalent extent as seen in the matching percentage saturation of transferrin and red cell ferritin levels . Interestingly , there is a discrepancy in the serum ferritin which is higher with the salt and this may reflect oxidative stress . Thirdly , corresponding efficacy can be achieved with better patient tolerance for the complex . Finally it is postulated that the iron polymaltose complex formulation more closely approximates the way in which enterocytes h and le dietary iron and thus physiologic regulatory mechanisms would be expected to reciprocally slow down absorption as stores exp and . Logically , therefore and , if confirmed , the latter finding suggests that this formulation may have a potential role in longer-term supplementation programmes BACKGROUND The efficacy of iron polymaltose complex ( IPC ) in the treatment of iron deficiency anemia ( IDA ) during pregnancy has not been well established , and the evidence is inconclusive . AIMS The aim of the study was to compare efficacy , safety , compliance , and cost-effectiveness of IPC with ferrous sulphate ( FS ) in pregnant patients . SETTING S AND DESIGN S The r and omized , double-blind , parallel-group study was conducted in the Department of Pharmacology in collaboration with the Department of Obstetrics and Gynaecology Postgraduate Institute of Medical Education and Research , Ch and igarh , India . METHODS One hundred pregnant women aged 20 - 40 years at 14 to 27 weeks ' gestation , with hemoglobin ( Hb ) < 9 g/dL , and serum ferritin < 12 mcg/L , were classified into 2 groups . One group received IPC ( 100 mg elemental iron ) , and the other group received FS ( 120 mg elemental iron ) daily for 8 weeks . At Week 0 and Week 8 , Hb , packed cell volume ( PCV ) , mean corpuscular volume ( MCV ) , mean corpuscular hemoglobin ( MCH ) , mean corpuscular hemoglobin concentration ( MCHC ) , serum iron , and serum ferritin were measured . Compliance with study medication was determined by pill counting at each visit . Cost minimization analysis was done to compare the costs of the 2 treatments . STATISTICAL ANALYSIS Data are expressed as mean -/+ SD . Paired and unpaired ' t ' test were used to analyze differences within groups and between groups . Chi-square ( x2 ) test was used to analyze primary efficacy parameters and adverse drug reactions ( ADR ) . RESULTS Statistically significant increases in Hb , PCV , MCV , MCH , MCHC , serum iron , and serum ferritin levels were seen at the end of 8 weeks of treatment in both groups . The overall adverse effects were more common in the FS group compared with the IPC group [ 41 ( 78 % ) vs 15 ( 31 % ) , P < .001 ] . The compliance rate was significantly ( P < .05 ) higher for the IPC ( 91 % ) group than for the FS ( 87 % ) group . The average total cost ( direct + indirect ) of treatment of anemia was comparable between the 2 groups . CONCLUSION The results of the present study suggest that IPC can be considered as a useful alternative formulation for the treatment of IDA during pregnancy for those patients who can not tolerate other iron preparations ( ferrous form ) ; this is an important finding , as compliance is a significant concern during pregnancy 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 Aims Patients with chronic heart failure ( CHF ) show impaired health-related quality of life ( HRQoL ) , an important target for therapeutic intervention . Impaired iron homeostasis may be one mechanism underlying the poor physical condition of CHF patients . This detailed sub analysis of the previously published FAIR-HF study evaluated baseline HRQoL in iron-deficient patients with CHF and the effect of intravenous ferric carboxymaltose ( FCM ) on HRQoL. Methods and results FAIR-HF r and omized 459 patients with reduced left ventricular ejection fraction and iron deficiency , with or without anaemia , to FCM or placebo ( 2:1 ) . Health-related quality of life was assessed at baseline and after 4 , 12 , and 24 weeks of therapy using the generic EQ-5D question naire and disease-specific Kansas City Cardiomyopathy Question naire ( KCCQ ) . Baseline mean Visual Analogue Scale ( VAS ) score was 54.3 ± 16.4 and KCCQ overall summary score was 52.4 ± 18.8 . Ferric carboxymaltose significantly improved VAS and KCCQ ( mean differences from baseline in KCCQ overall , clinical and total symptom scores , P < 0.001 vs. placebo ) at all time points . At Week 24 , significant improvement vs. placebo was observed in four of the five EQ-5D dimensions : mobility ( P= 0.004 ) , self-care ( P < 0.001 ) , pain/discomfort ( P= 0.006 ) , anxiety/depression ( P= 0.012 ) , and usual activity  ( P= 0.035 ) . Ferric carboxymaltose improved all KCCQ domain mean scores from Week 4 onward ( P≤ 0.05 ) , except for self-efficacy and social limitation . Effects were present in both anaemic and non-anaemic patients . Conclusions HRQoL is impaired in iron-deficient patients with CHF .  Intravenous FCM significantly improved HRQoL after 4 weeks , and throughout the remaining study period . The positive effects of FCM were independent of anaemia status
Conclusions All currently available intravenous iron preparations appear to be safe and effective , but ferric carboxymaltose seems to provide a better and quicker correction of haemoglobin and serum ferritin levels in iron-deficient patients
Background Iron deficiency is very common in a number of medical conditions .
Ferric carboxymaltose is a new stable iron preparation that can be administered in single infusions over short periods of time .
The aim of this study was to conduct a systematic review of r and omised controlled trials ( RCTs ) regarding the efficacy and safety of the novel complex compared with other iron formulations .
In addition , the feasibility of a network meta- analysis for indirect comparisons was investigated .