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Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Ferric Carboxymaltose in Chinese Patients with Iron-deficiency Anemia.
Ding, Y, Zhu, X, Li, X, Zhang, H, Wu, M, Liu, J, Palmen, M, Roubert, B, Li, C
Clinical therapeutics. 2020;(2):276-285
Abstract
PURPOSE Iron deficiency (ID) is one of the most commonly known nutritional deficiencies and is considered the primary cause of anemia (iron-deficiency anemia). Ferric carboxymaltose (FCM), an intravenous iron preparation, has been widely used for >10 years for iron-deficiency anemia treatment worldwide because of its many advantages. METHODS This single-center, open-label, single dose escalation study in Chinese subjects was designed to assess the pharmacokinetic/pharmacodynamic parameters and safety of FCM in this population. The first 12 subjects received a 500-mg dose; after assessing safety data from the first 6 subjects in this cohort, another 12 subjects were assigned to the 1000-mg dose cohort. FINDINGS After an infusion of FCM over 15 min, a rapid dose-dependent increase in total serum iron levels was observed with a median Tmax of 30 min following the start of the infusion for both cohorts. The Cmax and AUC for the 1000-mg dose were ~1.8-fold (p = 0.2929) and 2.3-fold (p = 0.0318) those associated with the 500-mg dose, respectively. Mean terminal t1/2 values were 12.3 and 10.5 h for the 2 cohorts. The renal elimination of FCM was negligible (<0.1%). Increase in mean serum iron levels and ferritin concentrations showed dose dependency. Iron-binding capacity was transiently well utilized after dosing, as indicated by transferrin saturation >88% with 500-mg FCM and >90% with 1000-mg FCM. Hemoglobin levels did not show significant changes during the 7-day observation period, whereas mean reticulocyte counts significantly increased in both cohorts, suggesting activation of the hematopoietic system. FCM was well tolerated in these Chinese subjects. No new or unexpected treatment-emergent adverse events were attributable to FCM. IMPLICATIONS The pharmacokinetic/pharmacodynamic and safety profiles in Chinese subjects seemed comparable to those in white and Japanese populations. ChinaDrugTrials.org.cn identifier: CTR20160863.
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Relationship between obesity and iron deficiency anemia: is there a role of hepcidin?
Sal, E, Yenicesu, I, Celik, N, Pasaoglu, H, Celik, B, Pasaoglu, OT, Kaya, Z, Kocak, U, Camurdan, O, Bideci, A, et al
Hematology (Amsterdam, Netherlands). 2018;(8):542-548
Abstract
OBJECTIVES Iron deficiency is common in obese children although the underlying mechanism is unclear. The aim of this study was to investigate the associations between iron parameters, leptin, hepcidin and adiponectin levels in obese children. METHODS A total of 237 children, ranging in age from 5 to 18 years, 180 with primary obesity and 57 healthy children and adolescents, were enrolled. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, leptin, hepcidin and adiponectin levels were studied. RESULTS White blood cell and platelet count, iron-binding capacity, high-sensitive C-reactive protein, leptin and hepcidin values in the obese group were higher than those of the control group (p < 0.001, p = 0.002, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). However, mean corpuscular volume, adiponectin and transferrin saturation values in the obese group were lower than in the control group (p = 0.026, p = 0.003, and p < 0.001, respectively). No significant differences were found in terms of hemoglobin, serum ferritin, iron and IL-6 levels. CONCLUSIONS Our study suggests that hepcidin levels do not contribute to the development of iron deficiency anemia in pediatric obese individuals.
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Safety and Efficacy of Intravenous Ferric Carboxy Maltose in Iron Deficiency Anaemia During Post-partum Period.
Mishra, V, Roy, P, Gandhi, K, Choudhary, S, Aggarwal, R, Sokabaj, S
Journal of Nepal Health Research Council. 2018;(3):208-211
Abstract
BACKGROUND Iron deficiency is the commonest treatable cause of postpartum anaemia. Parenteral iron therapy results in faster and higher replenishment of iron stores and correction of haemoglobin levels with better compliance. Ferric Carboxy Maltose is an effective and a safe option which can be administered intravenously in single total correction dose without any serious adverse effects.The study was done to evaluate the efficacy and safety of Ferric Carboxy Maltose in the treatment of iron deficiency anaemia in post-natal patients. METHODS It was an open, single arm study including 615 women with diagnosis of Iron deficiency anaemia and haemoglobin (Hb) levels between 4gm% and 11gm% from January 2013 to December 2016. Intravenous Ferric Carboxy Maltose(500-1500mg) was administered and the improvement in haemoglobin levels and iron stores were assessed after three weeks of total dose infusion. RESULTS Out of the 615 women, 595 women were included in the analysis. Most of the women were in the age group of 27-30 years. Most of the women had mild anaemia as per World Health Organisation guidelines. Mean hemoglobin levels significantly increased over a period of three weeks after Ferric Carboxy Maltose administration. Other parameters like total iron binding capacity, Ferritin and Iron also had a significant improvement after Ferric Carboxy Maltose administration. No serious adverse events were observed after Ferric Carboxy Maltose. CONCLUSIONS Intravenous Ferric Carboxy Maltose was an effective and a safe treatment option for iron deficiency anaemia and has an advantage of single administration of high doses without serious adverse effects.
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High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23.
Dahlerup, JF, Jacobsen, BA, van der Woude, J, Bark, LÅ, Thomsen, LL, Lindgren, S
Scandinavian journal of gastroenterology. 2016;(11):1332-8
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Abstract
OBJECTIVE Iron isomaltoside (Monofer(®)) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA. MATERIALS AND METHODS The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters. RESULTS Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found. CONCLUSION Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.
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Red Blood Cell Distribution Width and the Platelet Count in Iron-deficient Children Aged 0.5-3 Years.
Akkermans, MD, Uijterschout, L, Vloemans, J, Teunisse, PP, Hudig, F, Bubbers, S, Verbruggen, S, Veldhorst, M, de Leeuw, TG, van Goudoever, JB, et al
Pediatric hematology and oncology. 2015;(8):624-32
Abstract
Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5-3 years. ID was defined as serum ferritin (SF) <12 μg/L in the absence of infection (C-reactive protein [CRP] <5 mg/L) and IDA as hemoglobin <110 g/L combined with ID. RDW (%) and the platelet count were determined in the complete blood cell count. RDW was inversely correlated with SF and not associated with CRP. Calculated cutoff values for RDW to detect ID and IDA gave a relatively low sensitivity (53.1% and 57.1%, respectively) and specificity (64.7% and 69.9%, respectively). Anemic children with a RDW >14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2-6.3) to be iron deficient, compared with anemic children with a RDW <14.3%. The platelet count showed a large range in both ID and non-ID children. In conclusion, RDW can be helpful for identifying ID as the cause of anemia in 0.5- to 3-year-old children, but not as primary biomarker of ID(A). RDW values are not influenced by the presence of infection. There appears to be no role for the platelet count in diagnosing ID(A) in this group of children.
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The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention.
Bialkowski, W, Bryant, BJ, Schlumpf, KS, Wright, DJ, Birch, R, Kiss, JE, D'Andrea, P, Cable, RG, Spencer, BR, Vij, V, et al
Vox sanguinis. 2015;(2):178-85
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BACKGROUND AND OBJECTIVES Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. MATERIALS AND METHODS 'Strategies To Reduce Iron Deficiency' (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. RESULTS Iron deficient erythropoiesis was present in 52·7% of males and 74·6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0·002), but not more common in those receiving iron than placebo (P = 0·68). CONCLUSION The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo.
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Utilizing HDL levels to improve detection of celiac disease in patients with iron deficiency anemia.
Abu Daya, H, Lebwohl, B, Smukalla, S, Lewis, SK, Green, PH
The American journal of gastroenterology. 2014;(5):769-70
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Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial.
Kulnigg-Dabsch, S, Schmid, W, Howaldt, S, Stein, J, Mickisch, O, Waldhör, T, Evstatiev, R, Kamali, H, Volf, I, Gasche, C
Inflammatory bowel diseases. 2013;(8):1609-16
Abstract
BACKGROUND Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis. METHODS We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6. RESULTS A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression. CONCLUSION FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.
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Intravenous low molecular weight iron dextran in children with iron deficiency anemia unresponsive to oral iron.
Plummer, ES, Crary, SE, McCavit, TL, Buchanan, GR
Pediatric blood & cancer. 2013;(11):1747-52
Abstract
BACKGROUND Iron deficiency anemia (IDA) in children is usually treated with oral iron, yet many respond poorly. Intravenous low molecular weight iron dextran (LMWID) offers the opportunity of employing a single outpatient infusion to correct the anemia and reduce the overall burden of treatment, but its use in children has been limited due to concerns of serious adverse effects. In this study we report our initial experience using LMWID in children with iron deficiency in whom oral iron was ineffective. METHODS We performed a case series of LMWID treatment of children with IDA of diverse etiologies who were poorly responsive to oral iron therapy with the aim of measuring its efficacy and adverse effects. LMWID was administered as a total dose infusion over 60 minutes in the outpatient setting. RESULTS Thirty-one patients age 11 months to 18 years received intravenous LMWID, and 24 were evaluable for hematologic response. Median hemoglobin increments were respectively 3.5, 1.9, and 1.8 g/dl in patients with IDA due to poor nutrition (n = 11), chronic blood loss (n = 13), and miscellaneous causes (n = 7). Two thirds of evaluable patients had a complete hematologic response. Nine of the patients (29%) had mild non-specific adverse effects upon initiation of the LMWID infusion. CONCLUSIONS LMWID as a total dose infusion was well tolerated and effective in a heterogeneous group of children and adolescents with IDA who were refractory to oral iron therapy. Transient reactions were common but not serious.
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Glutathionyl hemoglobin is elevated in iron deficiency anemia.
Shet, AS, Pinto, SM, Mitra, G, Mandal, AK
Acta haematologica. 2012;(1):26-30
Abstract
There are few good biomarkers of iron deficiency anemia (IDA). Since IDA patients have evidence for increased oxidative stress, we used mass spectrometry (MS) [i.e. matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization] to identify novel biomarkers. Using MALDI-MS, the following oxidative modifications of hemoglobin with the following mass-to-charge ratios were identified: 1,087.5 (α32-40), 1,545.7 (α17-31), 1,290.0 (β31-40) and 2,076.1 (β41-59). On electrospray ionization MS, the IDA patients had significantly elevated glutathionyl hemoglobin (GSHb) compared with the controls (16.9 ± 9.6 vs. 7.7 ± 3.7%; p = 0.002). GSHb levels correlated inversely with serum ferritin (Spearman rho -0.485; p = 0.003) and positively with serum transferrin receptor (0.460; p = 0.002). GSHb also demonstrated inverse correlations with hemoglobin (-0.512; p = 0.001), mean cell volume (-0.419; p = 0.026), serum iron (-0.446; p = 0.008) and transferrin saturation (-0.460; p = 0.008). For the first time, we show that GSHb is elevated in patients with IDA and has potential as a biomarker of this form of anemia.