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Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.
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Anemia Ferropénica , Compuestos Férricos , Maltosa , Complicaciones Hematológicas del Embarazo , Humanos , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/uso terapéutico , Embarazo , Maltosa/análogos & derivados , Maltosa/administración & dosificación , Maltosa/uso terapéutico , Anemia Ferropénica/tratamiento farmacológico , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Administración Intravenosa , Ferritinas/sangre , Hemoglobinas/análisisRESUMEN
Abstract Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.
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Introducción: El hierro de administración intravenosa (iv) está indicado en los casos en que el tratamiento oral no es posible. El objetivo de este trabajo fue describir el perfil de uso, respuesta terapéutica y seguridad de la administración de hierro iv en el tratamiento de la anemia ferropénica en niños, niñas y adolescentes (NNA) asistidos en un centro de referencia de Uruguay entre 2018 y 2023. Método: Estudio retrospectivo mediante revisión de historias. Incluyó todos los NNA que recibieron hierro iv. Se registraron variables sociodemográficas, comorbilidades, clínica y severidad de la anemia. Se evaluó: motivos de la indicación y tipo de hierro iv, dosis, tiempo de infusión, respuesta terapéutica y efectos adversos. Resultados: Se incluyeron 35 pacientes, mediana de edad 4 años; 51,4% de sexo masculino, con comorbilidades 37,1%. Todos los menores de 3 años presentaban factores de riesgo para anemia ferropénica, la falta de adherencia al hierro oral se asoció con mayor severidad de la anemia (p<0,05). El motivo principal de indicación de hierro iv fue la severidad de la anemia e inadecuada respuesta al hierro oral concomitante en 37,1%. Todos recibieron hierro sacarato; mediana de dosis: 2 mg/kg y de tiempo de infusión: 1 hora. Se registró un caso de edema y exantema de cara vinculado a la rápida infusión. La evolución fue satisfactoria. Conclusiones: La administración de hierro iv fue segura. Es necesario establecer consensos respecto a la posología y monitorización. Se requieren nuevos estudios para continuar evaluando la eficacia y seguridad del hierro iv en sus diversas formulaciones.
Introduction: Intravenous (IV) iron administration it is indicated in cases where oral treatment is impossible. The objective of this work was to describe the profile of use, therapeutic response, and safety of the iron IV administration in treating anemia in children and adolescents (NNA) assisted in a reference center in Uruguay between 2018 and 2023. Method: Retrospective study through review of histories. It included all children and adolescents who received IV iron. Sociodemographic variables, comorbidities, clinical symptoms, and severity of anemia they were recorded. They were evaluated: reasons for the indication and type of IV iron, dose, infusion time, therapeutic response, and adverse effects. Results: we included 35 patients, with a median age of four years; 51.4% were male, and 37.1% had comorbidities. All children under three years of age had risk factors for iron deficiency anemia; greater severity of anemia was associated with lack of adherence to oral iron (p<0.05). The main reason for the indication of IV iron was the severity of anemia and inadequate response to concomitant oral iron at 37.1%. All received iron saccharate; median dose: 2 mg/kg and infusion time: 1 hour. A case of facial edema and rash linked to rapid infusion was recorded. The evolution was satisfactory. Conclusions: The administration of IV iron was safe. It is necessary to establish a consensus regarding dosage and monitoring. New studies are required to continue evaluating the efficacy and safety of IV iron in its various formulations.
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Contexto: la deficiencia de hierro es un trastorno frecuentemente observado en pacientes con enfermedad renal crónica (ERC), sobre todo en estadios avanzados. Su presencia se asocia a una mayor morbilidad y mortalidad. La deficiencia de hierro puede ser absoluta o funcional. La deficiencia absoluta se refiere a una ausencia o una reducción de las reservas de hierro, mientras que la deficiencia funcional se define por la presencia de depósitos de hierro adecuados pero con una disponibilidad insuficiente de hierro para su incorporación en los precursores eritroides. Varios factores de riesgo contribuyen a la deficiencia absoluta y funcional de hierro en ERC, incluyendo pérdidas hemáticas, absorción alterada de hierro e inflamación crónica. Objetivo: con esta revisión narrativa se pretende presentar las definiciones, los aspectos fisiopatológicos, los criterios diagnósticos y las medidas terapéuticas en el paciente con diagnóstico de ERC con deficiencia de hierro. Metodología: se realizó una revisión no sistemática de la literatura en la base de datos PubMed, incluyendo además las guías internacionales más utilizadas que abordan el tema de deficiencia de hierro en ERC. Resultados: se incluyeron un total de 30 referencias bibliográficas. La deficiencia de hierro puede ser absoluta o relativa y el déficit absoluto de hierro se produce con valores de ferritina 100 mcg/l, pero con una TSAT < 20 %. El tratamiento del déficit absoluto consta de reposición de hierro oral o endovenoso y en pacientes que aún no reciben diálisis, se puede hacer una prueba terapéutica con hierro oral, de no haber respuesta se optará por hierro endovenoso, mientras que en pacientes que sí reciben diálisis, la medida ideal es el hierro endovenoso, preferiblemente en preparaciones que permitan esquemas de altas dosis y bajas frecuencias de administración. Las metas propuestas por las distintas guías presentan variaciones entre 500 y 700 mcg/l de ferritina. Conclusiones: el déficit de hierro debe buscarse activamente en pacientes con ERC, ya que su presencia y la falta de intervención conlleva a un incremento en los desenlaces adversos. La terapia con hierro es el pilar del tratamiento y la elección del agente a utilizar dependerá de las características individuales del paciente y de la disponibilidad de las preparaciones de hierro oral o endovenoso.
Background: Iron deficiency is a disorder frequently observed in patients with chronic kidney disease (CKD), especially in advanced stages. Its presence is associated with increased morbidity and mortality. Iron deficiency can be absolute or functional. Absolute deficiency refers to absent or reduced iron stores, while functional deficiency is defined by the presence of adequate iron stores but insufficient iron availability for incorporation into erythroid precursors. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood fi, impaired iron absorption, and chronic inflammation. Purpose: With this narrative review, it is intended to present the details, pathophysiological aspects, diagnostic criteria and therapeutic options in patients diagnosed with chronic kidney disease with iron deficiency. Methodology: A non-systematic review of the fi ron ra was carried out, in the PubMed database, also including the most used international guidelines that address the issue fi ron deficiency in chronic kidney disease. Results: A total of 30 bibliographical references were included. Iron deficiency can be absolute or relative. The absolute iron deficiency occurs with ferritin values 100 mcg/l but with a TSAT <20 % Treatment of absolute deficiency consists of oral or intravenous iron replacement. In a patient who is not yet receiving dialysis, a therapeutic trial with oral iron can be done, if there is no response, intravenous iron will be chosen. In patients receiving dialysis, the ideal measure is intravenous iron, preferably in preparations that allow high-dose schemes and low frequencies of administration. The goals proposed by the different guidelines present variations between 500 and 700 mcg/l d ferritin. Conclusions: iron deficiency should be actively sought in patients with CKD, since its presence and lack of intervention leads to an increase in adverse outcomes. Iron therapy is the mainstay of treatment; the choice of the agent to be used depends on the individual characteristics of the patient and the availability of oral or intravenous iron preparations.
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Introducción El objetivo del estudio es pormenorizar los factores asociados a fracturas de cadera, prestando especial atención a las necesidades de transfusión de hemoderivados y sus factores de riesgo, así como su modificación a través del tratamiento preoperatorio mediante la administración de hierro intravenoso. Materiales y métodos Estudio observacional prospectivo de 119 pacientes ingresados por fractura de cadera. Descripción detallada del protocolo para la optimización prequirúgica de estos pacientes. Se recopilaron datos epidemiológicos, valores analíticos, así como datos acerca de la administración de hierro intravenoso y necesidad de transfusión. Resultados El 31,09% de los pacientes se encontraban antiagregados y el 21,85% estaban anticoagulados en el momento de la admisión. La hemoglobina media al ingreso fue de 12,5g/dl. El 43,2% se transfundieron durante la estancia hospitalaria. En el análisis de los factores de riesgo para la transfusión demostramos estadísticamente que tanto la hemoglobina al ingreso (p<0.001), como los diagnósticos previos de anemia crónica, hipertensión arterial e insuficiencia renal, tienen una relación con la necesidad de transfusión intrahospitalaria. Encontramos una relación estadísticamente significativa entre la administración de hierro y la cantidad de concentrados de hematíes trasfundidos (p<0.005). Los requerimientos de transfusión sanguínea fueron mayores en las fracturas extracapsulares que en las intracapsulares (p=0,024). Discusión Los pacientes con fractura de cadera presentan frecuentemente bajos niveles de hemoglobina al ingreso, así como comorbilidades y tratamientos que predisponen al desarrollo de anemia perioperatoria. La optimización preoperatoria de estos pacientes mediante la administración de hierro intravenoso podría reducir las necesidades transfusionales.
Background Aim of the study is to describe the elements associated with hip fractures about needs for transfusion of blood products and their risk factors, as well as their modification through preoperative treatment through the administration of intravenous iron. Material and methods A Cohort study of 119 patients admitted for hip fracture was conducted. Detailed description of the protocol for the pre-surgical optimization of these patients, epidemiological data, analytical values, as well as data on intravenous iron administration and need for transfusion were collected. Results 31.09% of the patients were using platelet aggregation inhibitors and 21.85% were were using anticoagulants at the time of admission. The mean hemoglobin on admission was 12.5g / dl. 43.2% were transfused during the hospital stay. In the analysis of risk factors for transfusion, we statistically demonstrated that both hemoglobin on admission (p <0.001), as well as previous diagnoses of chronic anemia, arterial hypertension, and renal failure, are related to the need for intra-hospital transfusion. We found a statistically significant relationship between iron administration and the amount of packed red blood cells transfused (p <0.005). Blood transfusion requirements were higher in extra-capsular than in intra-capsular fractures (p=0.024). Discussion Patients with hip fracture frequently present low hemoglobin levels upon admission, as well as comorbidities and treatments that predispose to the development of perioperative anemia. Preoperative optimization of these patients by administering intravenous iron could reduce transfusion requirements.
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Humanos , Fracturas de Cadera , Transfusión Sanguínea , Hemoglobinas , Hierro , AnticoagulantesRESUMEN
OBJECTIVE: To characterize barriers to and facilitators of successful iron therapy in young children with iron deficiency anemia (IDA) from an in-depth parental perspective. STUDY DESIGN: Prospective, mixed methods study of children age 9 months to 4 years with a diagnosis of nutritional IDA by clinical history and laboratory criteria and their parents. Clinical data were obtained from the electronic health record. Semistructured interviews focused on knowledge of IDA, clinical effects, experience with iron therapies, and motivation were conducted with the parent who identified as the child's primary caregiver. RESULTS: Twenty patient-parent dyads completed the study; 80% (n = 16) identified as Hispanic/Latino (white). Patients' median age was 23 months (50% male); median initial hemoglobin concentration was 8.2 g/dL and duration of oral iron therapy was 3 months. Parents' median age was 29 years (85% female); 8 interviews (40%) were conducted in Spanish. Barriers included difficulty in administering oral iron owing to side effects and poor taste. Facilitators included provision of specific instructions; support from healthcare providers and additional caregivers at home; motivation to benefit child's health, which was strengthened by strong emotional reactions (ie, stress, anxiety) to therapy and follow-up; and an appreciation of child's improvement with successful completion of therapy. CONCLUSIONS: Our findings support the need for interventions designed to promote oral iron adherence in children with IDA. Rather than focusing on knowledge content related to IDA, interventions should aim to increase parental motivation by emphasizing the health benefits of adhering to iron therapy and avoiding more invasive interventions.
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Anemia Ferropénica/tratamiento farmacológico , Hierro/administración & dosificación , Administración Oral , Adulto , Preescolar , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Lactante , Masculino , Padres , Estudios ProspectivosRESUMEN
OBJECTIVES: To evaluate the therapeutic response and adverse effects of Noripurum EV® in children and adolescents with inflammatory bowel disease (IBD) and iron deficiency anemia. MATERIALS AND METHODS: Cohort study involving patients with Crohn's disease (CD) and ulcerative colitis (UC) who received treatment for iron deficiency anemia with Noripurum EV®. Anemia was defined according to WHO 2011 criteria. Iron deficiency anemia was established when ferritin <30µg/l and transferrin saturation <16%. Iron deficiency anemia and anemia of chronic disease were established when ferritin was between 30 and 100µg/l and transferrin saturation <16%. The total dose of Noripurum EV® was estimated by the Ganzoni formula and divided into weekly administrations. When there was an increase in hemoglobin (Hb) by a minimum of 2g/dl and or when Hb reached the target determined by WHO, treatment was considered a therapeutic success. RESULTS: Noripurum EV® was administered to 16 patients (9.3% of total patients with IBD). Ten (65.5%) were male, the mean (SD) age was 11.3(4.6) years old, 75%(12/16) had CD and 25%(4/16) had UC. All patients presented an increase in Hb (p < .001) at a mean (SD) of 2.8(1.3)g/dl, after median and interquartile range(IQR) of 4.5(3.0-6.0) weeks that iron infusions were completed. It was found that the proportion of patients that achieved therapeutic success (68.8%) was statistically higher (p = .031) than those who did not (31.2%). No adverse events were reported. CONCLUSION: Noripurum EV® in pediatric patients with IBD and iron deficiency anemia was effective and safe, making it an appropriate option for the clinical management of these patients.
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Anemia Ferropénica/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Compuestos Férricos/uso terapéutico , Hematínicos/uso terapéutico , Administración Intravenosa , Adolescente , Brasil , Niño , Estudios de Cohortes , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/efectos adversos , Ferritinas/sangre , Hematínicos/administración & dosificación , Hematínicos/efectos adversos , Hemoglobinas/metabolismo , Humanos , Masculino , Calidad de Vida , Índice de Severidad de la Enfermedad , Transferrina/metabolismoRESUMEN
BACKGROUND: Iron deficiency anemia is a disease that can significantly compromise a patient's quality of life. Desensitization is a safe and effective treatment option for iron-deficient anemic patients who require intravenous iron despite their hypersensitivity to iron. This report describes a safe desensitization protocol for patients with iron hypersensitivity who require iron treatment for their clinical improvement. CASE PRESENTATION: Two patients of 20 and 46-year-old diagnosed with secondary iron deficiency anemia hipermenorreas and a clinical history of fail treatment with oral iron, who presented a reaction of the anaphylactic type while they receive iron parenteral sucrose. Therefore, the patients were treated with the desensitization protocol applied for patients with hypersensitivity to iron. CONCLUSION: Iron deficiency anemia is a disease that can significantly compromise the quality of life of patients. The desensitization protocol for patients with hypersensitivity to iron is a safe and effective treatment option for patients with a history of allergy to intravenous iron. This case report shows the usefulness to use the desensitization protocol for patients with hypersensitivity to iron.
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Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control). Rats treated with LMWID, FMX, or IIM showed significant changes in most measures of oxidative/nitrosative stress, inflammation, and iron deposition compared to the saline-treated controls, with greatest changes in the LMWID treatment group. Increases in products of lipid peroxidation (thiobarbituric acid reactive substances) and protein nitrosation (nitrotyrosine) were consistent with increases in the activity of antioxidant enzymes (catalase, Cu,Zn-SOD, GPx), decreases in antioxidative capacity (reduced:oxidized GSH ratio), increased levels of transcription factors involved in the inflammatory pathway (NF-κB, HIF-1α), inflammatory cytokines (TNF-α, IL-6), adhesion molecules (VCAM-1), markers of macrophage infiltration (ED-1), and iron deposition (Prussian blue, ferritin). Since changes in measured parameters in FCM- or IS-treated rats were generally modest, the results suggest that FCM and IS have a low propensity to induce lung inflammation. The relevance of these findings to clinical safety profiles of the tested intravenous iron products requires further investigation.
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Inflamación/inducido químicamente , Compuestos de Hierro/toxicidad , Pulmón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Administración Intravenosa , Animales , Biomarcadores/análisis , Relación Dosis-Respuesta a Droga , Femenino , Inflamación/metabolismo , Compuestos de Hierro/administración & dosificación , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratas , Ratas Sprague-DawleyAsunto(s)
Anemia Ferropénica , Hierro , Adolescente , Niño , Compuestos Férricos , Humanos , Maltosa/análogos & derivadosRESUMEN
ABSTRACT Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.
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Anemia Ferropénica/terapia , Inyecciones Intravenosas/estadística & datos numéricos , /terapia , Neoplasias/complicacionesRESUMEN
Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.
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INTRODUCTION: Ferric carboxymaltose is a next-generation polynuclear iron(III)-hydroxide carbohydrate complex for intravenous iron therapy belonging to the class of so-called non-biological complex drugs. The product characteristics and therapeutic performance of non-biological complex drugs are largely defined by the manufacturing process. A follow-on product, termed herein as ferric carboxymaltose similar, is available in India. Given that non-biological complex drugs may display differences in diverse product properties not characterisable by physico-chemical methods alone. AIM: The aim is to assess the effects of this ferric carboxymaltose similar in our non-clinical model in non-anaemic healthy rats. MATERIALS AND METHODS: Non-anaemic rats were treated with intravenous ferric carboxymaltose similar or iron sucrose both at (40 mg iron/kg body weight), or with saline solution (control) for four weeks, after which the animals were sacrificed. Parameters for tissue iron distribution, oxidative stress, nitrosative stress, inflammation and apoptosis were assessed by immunohistomorphometry. RESULTS: Ferric carboxymaltose similar resulted in deranged iron distribution versus iron sucrose originator as indicated by increased serum iron, transferrin saturation and tissue iron(III) deposits as well as decreased ferritin deposits in the liver, heart and kidneys versus iron sucrose originator. Ferric carboxymaltose similar also increased significantly oxidative/nitrosative stress, pro-inflammatory, and apoptosis markers in the liver, heart and kidneys versus iron sucrose originator. CONCLUSION: In our rat model, ferric carboxymaltose similar had a less favourable safety profile than iron sucrose originator, adversely affecting iron deposition, oxidative and nitrosative stress, inflammatory responses, with impaired liver and kidney function.
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With the challenge of optimizing iron delivery, new intravenous (iv) iron-carbohydrate complexes have been developed in the last few years. A good example of these new compounds is ferric carboxymaltose (FCM), which has recently been approved by the US Food and Drug Administration for the treatment of iron deficiency anemia in adult patients who are intolerant to oral iron or present an unsatisfactory response to oral iron, and in adult patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). FCM is a robust and stable complex similar to ferritin, which minimizes the release of labile iron during administration, allowing higher doses to be administered in a single application and with a favorable cost-effective rate. Cumulative information from randomized, controlled, multicenter trials on a diverse range of indications, including patients with chronic heart failure, postpartum anemia/abnormal uterine bleeding, inflammatory bowel disease, NDD-CKD, and those undergoing hemodialysis, supports the efficacy of FCM for iron replacement in patients with iron deficiency and iron-deficiency anemia. Furthermore, as FCM is a dextran-free iron-carbohydrate complex (which has a very low risk for hypersensitivity reactions) with a small proportion of the reported adverse effects in a large number of subjects who received FCM, it may be considered a safe drug. Therefore, FCM appears as an interesting option to apply high doses of iron as a single infusion in a few minutes in order to obtain the quick replacement of iron stores. The present review on FCM summarizes diverse aspects such as pharmacology characteristics and analyzes trials on the efficacy/safety of FCM versus oral iron and different iv iron compounds in multiple clinical scenarios. Additionally, the information on cost effectiveness and data on change in quality of life are also discussed.
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Anemia Ferropénica/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Compuestos Férricos/administración & dosificación , Compuestos Férricos/uso terapéutico , Maltosa/análogos & derivados , Humanos , Maltosa/administración & dosificación , Maltosa/uso terapéuticoRESUMEN
Las interacciones entre el corazón y el riñón se han convertido en un área de considerable interés, dada la interdependencia de los mismos. Esto motivó la definición y conceptualización del síndrome cardio-renal anémico, que incluye interacciones bidireccionales, donde alteraciones, tanto agudas como crónicas de cualquier órgano, pueden afectar indistintamente la función renal o la ventricular. El tratamiento, involucra el bloqueo del eje renina angiotensina aldosterona y durante una descompensación aguda es válido el soporte dialítico para control de la volemia. La anemia, es multifactorial, se debe tratar de manera oportuna con hierro endovenoso y eritropoyetina recombinante, reduciendo al mínimo el soporte transfusional. El manejo, la definición y el pronóstico del síndrome cardio-renal anémico aún sigue siendo controversial y es un reto para el internista moderno (Acta Med Colomb 2011; 36: 141-144).
The interactions between the heart and the kidney have become an area of considerable interest, given their interdependence. This led to the definition and conceptualization of cardio-renal anemic syndrome, which includes a bidirectional interaction: acute or chronic injuries of any organ indiscriminately affect renal or ventricular function. Treatment involves blocking the rennin-angiotensin-aldosterone axis and, during acute decompensation, dialytic support for volemic control. Anemia is due to multiple causesand must be treated promptly with intravenous iron and recombinant erythropoietin, to minimize the need for transfusions. Management, definition and prognosis of cardio-renal anemic syndrome are still controversial and represent a challenge for the modern internist (Acta Med Colomb 2011; 36: 141-144).
RESUMEN
A pesar del amplio uso del hierro endovenoso en hemodiálisis, resta aún identificar un índice adecuado para optimizar esta terapéutica en el largo plazo. Con ese objetivo, se diseñó un estudio prospectivo de cohorte, de larga duración, que consistió en un período basal (PB) y dos períodos experimentales: PI y PII. Se infundió hierro dextran de bajo peso molecular a 100, 150 y 200 mg/mes, respectivamente, durante 6 meses y al final de cada periodo se determinaron: saturación de transferrina (TSAT), ferritina (FERR), porcentaje de eritrocitos hipocrómicos (HYPO) y contenido de hemoglobina en reticulocitos (HCr). Durante el estudio la albúmina aumentó significativamente, pero la Hgb, la dosis de EPO y la proteína C-reactiva se mantuvieron sin cambios. Los cambios en HYPO y FERR fueron inespecíficos. Sólo TSAT (desde 21.4 ± 6 en PB a 34 ± 7.1% en PII, p = 0.01) y HCr (desde 27.5 ± 1.3 en PB a 29.3 ± 1.7 pg en PII, P = 0.045) respondieron específicamente, pero el porcentaje de aumento de TSAT fue de 65% (IC95% 22), y el de HCr sólo 6% (IC95% 2.3; p = 0.0002). Esta diferencia a favor de TSAT se observó en todos los pacientes. Los resultados sugieren la utilización de 200 mg/FeIV/mes y que, de los índices estudiados, TSAT sería el más adecuado para optimizar el uso a largo plazo del hierro endovenoso en hemodiálisis.
The usefulness of intravenous iron therapy in hemodialysis is evidence-based. However, controversy still arises about the most suitable iron marker to optimize this treatment in the long term. We aimed to determine the most suitable marker with a prospective, cohort study, designed to comprise a basal period (BP) and two consecutive experimental periods (PI, PII). Low molecular weight iron dextran was infused at 100, 150 and 200 mg/month respectively, on a biweekly basis, during 6 months. At the end of each period, the following were determined: transferrin saturation (TSAT), ferritin (FERR), percentage of hypochromic eritrocytes (HYPO) and haemoglobin content in reticulocytes (HCr). During the study, albumin increased significantly, whereas no significant changes in hemoglobin, EPO doses and C-reactive protein were observed. Changes in HYPO and FERR were unspecific. Only TSAT (from 21.4 ± 6 in PB to 34 ± 7.1% in PII, p < 0.01) and HCr (from 27.5 ± 1.3 in PB to 29.3 ± 1.7 pg in PII, P < 0.05 ) responded specifically to changes in Fe doses, but change of TSAT was 65% (CI 95% 22), whereas change of HCr was just 6% (CI 95% 2.3; p = 0.0002). The difference was observed in all patients. Results suggest that 200 mg/FeIV/month is effective and that, of the markers tested in this study, TSAT would be the most suitable one to the practicing nephrologist to optimize intravenous iron in the long term.
Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anemia Ferropénica/tratamiento farmacológico , Complejo Hierro-Dextran/administración & dosificación , Diálisis Renal/efectos adversos , Transferrina/análisis , Anemia Ferropénica/sangre , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Métodos Epidemiológicos , Hematínicos/administración & dosificación , Infusiones IntravenosasRESUMEN
O objetivo desse estudo foi avaliar a eficácia do uso intravenoso de sacarato de hidróxido de ferro III no tratamento de pacientes adultos com anemia ferropriva. No período de janeiro de 2003 a dezembro de 2005, estudamos cinqüenta pacientes com anemia ferropriva que apresentaram intolerância e/ou resposta inadequada ao tratamento com ferro por via oral e/ou valor de hemoglobina inferior a 7,0 g/dL. Os principais exames laboratoriais realizados foram: hemograma completo, contagem de reticulócitos, ferro sérico, capacidade total de ligação de ferro e ferritina sérica. Os pacientes receberam uma dose semanal de 200 mg de sacarato de hidróxido de ferro III diluído em 250 mL de soro fisiológico a 0,9 por cento, administrado por via intravenosa em trinta minutos. O tratamento foi realizado até a obtenção do valor de hemoglobina igual ou maior que 12,0 g/dL para mulheres e 13,0 g/dL para homens, ou até a administração da dose total de ferro parenteral recomendada para cada paciente. A idade mediana dos cinqüenta pacientes estudados foi de 45 anos, variando entre 28 e 76 anos; quarenta (80,0 por cento) eram do sexo feminino. A causa mais comum de anemia ferropriva no sexo feminino foi sangramento uterino anormal observado em 25/40 pacientes (62,5 por cento) e, no sexo masculino, gastrectomia parcial em 7/10 (70,0 por cento). Vinte e quatro (48,0 por cento) pacientes foram incluídos nesse estudo por falta de resposta à terapia com ferro oral, 22 (44,0 por cento) por intolerância ao ferro oral e quatro (8,0 por cento) por hemoglobina < 7,0 g/dL. Os valores médios da hemoglobina e da ferritina sérica foram de 8,48 g/dL e 4,65 ng/mL (pré-tratamento) e 12,34 g/dL e 93,20 ng/mL (pós-tratamento)(p<0,001), respectivamente. O aumento médio de hemoglobina foi de 3,61 g/dL e de 4,83 g/dL para os sexos feminino e masculino, respectivamente. Correção da anemia foi obtida em 26 (65,0 por cento) das quarenta pacientes do sexo feminino e em nove (90,0 por cento)...
The objective of this study was to evaluate the efficacy of intravenous iron III-hydroxide saccharate to treat adult patients with iron deficiency anemia. Between January 2003 and December 2005 we studied 50 patients with iron deficiency anemia who presented intolerance or inadequate response to oral iron therapy, or hemoglobin level < 7 g/dL. The main laboratory tests performed were: complete blood cell count, reticulocyte count, serum iron, total iron-binding capacity and serum ferritin. The patients received a weekly dose of 200 mg of iron diluted in 250 mL of 0.9 percent sodium chloride solution administered intravenously during 30 minutes. It was performed until a hemoglobin level = 12.0 g/dL for women or13.0 g/dL for men was reached or completing the administration of the total dose of parenteral iron recommended for each patient. The median age of the patients studied was 45 years (age range from 18 to 76). Forty out of 25 patients (80 percent) were women. The most common cause of iron deficiency anemia was abnormal uterine bleeding observed in 62.5 percent of female patients (25 out of 40) and partial gastrectomy in 70 percent of male patients (7 out of 10). Twenty-four (48 percent) patients were included in this study due to a lack of response to oral iron therapy, 22 (44 percent) showed intolerance to oral iron and 2 (8 percent) presented with a hemoglobin level < 7.0 g/dL. The mean hemoglobin and ferritin values were 8.48 g/dL and 4.65 ng/mL (pretreatment) and 12.34 g/dL and 93.20 ng/mL (post-treatment) (p<0.001), respectively. The average increase of hemoglobin was 3.61 g/dL and 4.83 gdL for women and men, respectively. Correction of anemia was obtained in 26 out of 40 female patients (65 percent) and in 9 out of 10 male patients (90 percent). Six patients received blood transfusions before starting intravenous iron treatment. None of the 50 studied patients needed red blood cell transfusions during or after completing...
Asunto(s)
Anemia Ferropénica , Hemoglobinas , Administración Intravenosa , Sacarato de Óxido Férrico , AnemiaRESUMEN
Anemia is a frequent complication of CKD and has numerous physiologic effects. In the treatment of anemia it is important to guarantee adequate iron storesfor hemoglobin synthesis. The aim of this study is to report on the impact of iron reposition on hemoglobin levels in patients with CKD stages 3 to 5. Fortyanemic patients (hemoglobin <11.0 g/dL) with CKD stages 3 (17,5%), 4 (58,5%), and 5 (25%), not receiving re-Hu-Erithropoetin were treated with IV iron(Noripurum, Altana Pharma), a ferric sucrose product. Iron deficiency was diagnosed when transferrin saturation was <20% and/or ferritin <100 mg/L. TheIV Iron (100 mg/ ampoules) was given in 150 mL of saline over 90 minutes. Glomerular filtration rate (GFR) was estimated from serum creatinine using theMDRD formula, and patients were categorized according to the stages defined by K/DOQI of the NKF. The mean age of the patients was 58.6±17 yearsand 56% were female. The main causes of CKD were hypertension (33.0%), diabetes mellitus (19.0%) and glomerulonephritis (19.0%). The mean valuesof the lab results before and after the IV iron administration were: creatinine (2.79±1.28 and 3.01±1.84, p>0.90), GFR (25.92±13.4 and 26.14±13.34, p>0.29), serum iron (58.3±28 and 90.9, p>0.60), transferrin saturation index (22.94±11.36 and 27.4±8, p>0.49), ferritin (84.69±78.3 and 164.8±141, p<0.04) andhemoglobin (9.52±1.24 and 10.53±1.44, p<0.000). The mean amount of IV iron sucrose administered was 319±180mg. The IV iron was very well toleratedand no serious side effect was observed. In conclusion, administration of IV Noripurum, a dextran-free iron compound, was safe and showed a beneficial impact on the hemoglobin level, and its use optimized the treatment of anemia in patients with CKD.
A anemia é uma complicação freqüente na doença renal crônica (DRC) e determina vários efeitos fisiológicos. No tratamento da anemia, é importantegarantir a reserva de ferro adequada para a síntese de hemoglobina. O objetivo deste trabalho é relatar sobre o impacto da reposição de ferro nos níveisde hemoglobina em pacientes com anemia decorrente da DRC na fase pré-dialítica. Quarenta pacientes anêmicos (hemoglobina <11,0g/dL) com DRCestágios 3 (17,5%), 4 (58,5%) e 5 (25%), não tratados com eritropoetinina humana recombinante, receberam ferro venoso (sacarato de hidróxido de ferroIII, Noripurum, ALTANA Pharma). A deficiência de ferro foi diagnosticada quando o índice de saturação da transferrina (%) foi inferior <20%, associado ounão à ferritina (mg/dL) <100mg/dL. O ferro endovenoso foi administrado na dose de 100mg diluído em 150mL de soro fisiológico no período de 90 minutos.A filtração glomerular (mL/min/1,73m2) foi estimada a partir da creatinina sérica (mg/dL) através da fórmula do estudo MDRD e os pacientes foramestagiados segundo as diretrizes brasileiras sobre DRC e o K/DOQI da National Kidney Foundation. A idade média dos pacientes foi de 58,6 ±17 anos,sendo 56% do sexo feminino. As principais causas de DRC foram hipertensão arterial (33,0%), diabetes mellitus (19,0%) e glomerulonefrites (19,0%). Osvalores médios dos resultados laboratoriais antes da reposição de ferro e após foram: creatinina (2,79±1,28mg/dL e 3,02±1,84mg/dL, p= 0,90), FG(25,92±13,4mL/min/1,73m2 e 26,14±13,34mLmin/1,73m2, p= 0,29), ferro sérico (58,3±28 e 90,9±35, p= 0,60), índice de saturação da transferrina(22,94±11,36% e 27,40±8,0, p= 0,49), ferritina (84,69±78,3 e 164,8±13,34, p<0,004) e hemoglobina (9,52±1,24g/dL e 10,53±1,44, p<0000). A quantidademédia de sacarato de hidróxido de ferro III administrada foi de 319±178mg.