[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation.

Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes. We therefore investigated the core-ligand structure of two clinically relevant iron-carbohydrate complexes, iron sucrose (IS) and ferric carboxymaltose (FCM), and their interactions with two structurally different human plasma proteins, human serum albumin (HSA) and fibrinogen, using a combination of cryo-scanning transmission electron microscopy (cryo-STEM), x-ray diffraction (XRD), small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS). Using this orthogonal approach, we defined the nano-structure, individual building blocks and surface morphology for IS and FCM. Importantly, we revealed significant differences in the surface morphology of the iron-carbohydrate complexes. FCM shows a localised carbohydrate shell around its core, in contrast to IS, which is characterised by a diffuse and dynamic layer of carbohydrate ligand surrounding its core. We hypothesised that such differences in carbohydrate morphology determine the interaction between iron-carbohydrate complexes and proteins and therefore investigated the NPs in the presence of HSA and fibrinogen. Intriguingly, IS showed significant interaction with HSA and fibrinogen, forming NP-protein clusters, while FCM only showed significant interaction with fibrinogen. We postulate that these differences could influence bio-response of the two formulations and their clinical outcome. In conclusion, our study provides orthogonal characterisation of two clinically relevant iron-carbohydrate complexes and first hints at their interaction behaviour with proteins in the human bloodstream, setting a prerequisite towards complete understanding of the correlation between physicochemical properties and clinical outcome.

Carboximaltosa férrica en pacientes con insuficiencia cardíaca con fracción de eyección reducida y deficiencia de hierro previo cirugía cardiovascular / Ferric carboxymaltose in patients with heart failure with reduced exercise fraction and iron deficiency before cardiovascular surgery

ÁREA DESCRIPTIVA DEL PROBLEMA DE SALUD: Definición: La anemia y la ferropenia son dos importantes comorbilidades comunes en pacientes con Insuficiencia Cardíaca (IC) y se asocian a un mal estado clínico y a peores resultados a corto y largo plazo; la anemia y la ferropenia son de hecho, medidores de pobre pronóstico en pacientes con IC, corregir estas comorbilidades sería una diana terapéutica atractiva y novedosa para mejorar los resultados. La anemia se asocia de forma independiente con la gravedad de la IC y la mortalidad, y la deficiencia de hierro parece asociarse de forma exclusiva con una menor capacidad de ejercicio. La deficiencia de hierro suele definirse como un nivel de ferritina <100 µg /L o un nivel de 100 a 300 µg/L, si la saturación de transferrina es <20%. Se ha demostrado que la repleción intravenosa de hierro mejora la capacidad de ejercicio y la calidad de vida. Principales manifestaciones clínicas: la identificación de los síntomas es un paso clave en el diagnóstico; estos incluyen aquellos relacionados a la sobrecarga hídrica (disnea, ortopnea, edema, dolor por la congestión hepática, y discomfort abdominal asociado a la distensión por la ascitis) y aquellos secundarios a la reducción del gasto cardíaco (debilidad, fatiga) que se pronuncian más con el ejercicio.(2) En cuanto a la anemia, definida como la reducción de 1 o más componentes de la línea roja celular (concentración de hemoglobina, hematocrito, o conteo de glóbulos rojos) una concentración baja de hemoglobina o bajo hematocrito son los parámetros ampliamente usados para el diagnóstico, con los siguientes rangos. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas Pubmed Carboximaltosa férrica; Insuficiencia cardiaca; Deficiencia de hierro; Hierro Sacarosa; Anemia; cirugía cardiovascular. Se filtra la búsqueda a Estudios Clínicos fase 111, controlados randomizados, Revisiones Sistemáticas, Meta-análisis, Guías de Práctica Clínica, además se limitó la búsqueda estudios en humanos. También se realiza búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP 0ATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, meta-análisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES. Eficacia: Carboximaltosa Férrica es un medicamento propuesto para el tratamiento de pacientes con anemia por déficit de hierro, en quienes no se puede corregir esta afección con hierro oral, o se necesita hacerlo de una manera rápida; La evaluación de este efecto se ha hecho a través de ensayos clínicos controlados y aleatorizados. Estos estudios sugieren que el uso de carboximaltosa férrica puede ser eficaz para corregir la anemia secundaria por déficit de hierro, pero es importante recalcar que los estudios pivotales están hechos comparando su uso con placebo; la utilización se asocia con mejoría en la calidad de vida de estos pacientes y menos tiempo de estancia hospitalaria; sin embargo, estos mismos informes refieren que no hay disminución en la probabilidad de muerte en general para estos pacientes; es muy importante mencionar que a pesar de que la carboximaltosa férrica al momento está siendo muy estudiada para el uso de pacientes con déficit de hierro e insuficiencia cardíaca, los preparados como Hierro Sacarosa también han sido estudiados en esta patología , y faltan más investigaciones donde se comparen estos dos preparados para obtener mayor evidencia sobre el beneficio de usar uno sobre el otro; además, también hay una gran falta de estudios específicos sobre la población preoperatoria que se someterá a cirugía cardiovascular; si bien es cierto se hace un especial énfasis acerca de la importancia de identificar y corregir la anemia preoperatoria, las guías clínicas actualizadas y revisiones de la literatura no especifican a la carboximaltosa férrica como medicamento de primera línea en el manejo de los pacientes sometidos a cirugía cardiovascular. También, es de hacer notar que la mayoría de investigaciones se han realizado en poblaciones específicas que no pueden ser generalizados a otras poblaciones, así como hay heterogeneidad en los parámetros estudiados entre ellos como los valores de hemoglobina en cada estudio siendo un dato importante para esta revisión. Seguridad: De acuerdo a la revisión realizada se puede concluir que la administración de Carboximaltosa férrica es segura; La reacción adversa reportada con mayor frecuencia fue náuseas (que se produce en el 3,2% de los sujetos), seguida por reacciones en el lugar de inyección/perfusión, hipofosfatemia, cefalea, rubefacción, mareos e hipertensión. Las reacciones en el lugar de inyección/perfusión se componen de varias reacciónes adversas que de forma individual son poco frecuentes o raras. La más grave es la reacción anafiláctica (rara); se han notificado muertes con su uso; los estudios también demuestran que ambas terapias presentan reacciones similares, siendo las más comunes los trastornos de hipersensibilidad, gastrointestinales y desequilibrios hidroelectrolíticos. Aunque es cierto que la literatura describe un ligero aumento en la frecuencia de estas reacciones con Hierro Sacarosa, también se menciona que la mayoría de ellas son rápidamente reversibles y no ponen en peligro la vida de los pacientes. Costo: Para el ISSS, el uso de Carboximaltosa Férrica en pacientes con Insuficiencia Cardíaca y anemia podría considerarse una opción rentable a largo plazo. Dado que se requiere una única aplicación y menos personal y espacio hospitalario, el costo de adquisición se puede recuperar a través de la reducción de recursos de salud utilizados y la ocupación de camas hospitalarias. Aunque al comparar el costo de adquisición de este medicamento con Hierro Sacarosa, un medicamento ya disponible en la institución, se observa que, a pesar de que se necesitan dosis mayores de Hierro Sacarosa para lograr el mismo efecto, el costo total de estas dosis no supera la aplicación individual de Carboximaltosa Férrica. Conveniencia: A pesar de lo antes mencionado sobre el beneficio del uso de carboximaltosa de hierro, en pacientes con déficit de hierro e insuficiencia cardíaca; La mayoría de documentos mencionan que el hierro intravenoso podría controlar los niveles de hemoglobina en los pacientes sometidos a cirugía electiva, no está clara la repercusión del hierro intravenoso sobre los resultados (transfusiones sanguíneas, riesgo de infecciones, o supervivencia en general). En la institución se cuenta con Hierro Sacarosa, un preparado endovenoso que también se utiliza para la corrección de la anemia por déficit de hierro; las ventajas que se presentan de la carboximaltosa férrica a este preparado se centran en menor número de dosis y menor estancia hospitalaria, que se traducen en menor uso de recursos y menor tiempo cama hospitalaria; sin embargo, no hay estudios que prueben el beneficio en una rápida corrección de hemoglobina utilizando carboximaltosa férrica sobre hierro sacarosa, por lo que no es posible concluir que sea más conveniente su uso en pacientes preoperatorios que necesiten un rápido restablecimiento de estos valores.

Comparison of different intravenous iron preparations in terms of total oxidant and total antioxidant status, single center data.

Iron deficiency anemia is the most common and preventable cause of anemia. Oral and parenteral iron preparations can be used for treatment. There are some concerns about the effect on oxidative stress of parenteral preparations. In this study, we aimed to investigate the effect of ferric carboxymaltose and iron sucrose on short- and long-term oxidant-antioxidant status. The study was designed as a prospective, single-center, observational study. Patients diagnosed with iron deficiency anemia and receiving intravenous iron therapy were included. Patients were divided into 3 groups as those receiving 1000 mg iron sucrose, 1000 mg ferric carboxymaltose, and 1500 mg ferric carboxymaltose. Blood samples were collected for blood tests before treatment, at the 1st hour of the first infusion, and at the 1st month of follow-up. The total oxidant and total antioxidant status were analyzed to evaluate oxidative stress and antioxidant status. Fifty-eight patients are included. Nineteen patients received iron sucrose 1000 mg (G1), 21 patients received ferric carboxymaltose 1000 mg (G2), and 18 patients received ferric carboxymaltose 1500 mg (G3). First hour total antioxidant status was higher in the iron sucrose group than in the ferric carboxymaltose group [G1 and G2 (p = 0.027), G1 and G3 (p = 0.004)]. At the 1st hour, total oxidant status was higher in iron sucrose group than in ferric carboxymaltose group [G1 and G2 (p = 0.016), G1 and G3 (p = 0.011)]. There was no difference in total oxidant and antioxidant stress between the three treatment groups at the 1st month evaluation [p: 0.19 and p: 0.12]. Total oxidant and antioxidant status in iron sucrose and ferric carboxymaltose formulations were found to be higher in the iron sucrose group in the acute period at the 1st hour after infusion. There was no significant difference between antioxidant and oxidant total status in all three treatment groups at the 1st month of long-term control. The fact that total oxidant status was lower in the ferric carboxymaltose group containing high-dose treatment compared to iron sucrose according to the 1st hour change showed that high-dose iron did not significantly affect oxidant stress in the short term. In addition, long-term oxidant stress evaluation at the 1st month did not show any difference between iron preparations. In conclusion, it has been shown that high-dose intravenous iron therapy, which is easier to use in clinical practice, has no effect on the oxidant-antioxidant system.

Intravenous Iron Therapy for Children With Iron Deficiency Anemia.

Iron deficiency anemia in children is a public health problem. Although oral iron treatment is the first choice, common side effects and compliance problems can cause the treatment to be interrupted. This study retrospectively evaluated children treated with intravenous (IV) iron sucrose or ferric carboxymaltose (FCM) and compared the treatment processes and efficacy. The demographic characteristics and treatment details of the 44 children with iron deficiency anemia were retrospectively evaluated. Iron sucrose was administered to 25 patients and FCM was administered to 19 patients. The IV iron infusion was applied to 64% of the patients because of unresponsiveness to oral treatment, 25% of the patients because of compliance problems, and 11% of the patients because of severe anemia. IV iron therapy increased hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, red-cell distribution width, and serum ferritin levels and decreased platelet count. The mean number of infusions per patient in the FCM group was lower, and the total treatment time was shorter. In conclusion, IV iron sucrose or FCM can be used in children with nonadherence to oral therapy and severe anemia in addition to specific indications.

Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

BACKGROUND: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. RESULTS: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. CONCLUSIONS: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.

Decreased Clinical Toxicity and Two-Phase Elimination Kinetics Observed After Intravenous Iron Sucrose Overdose.

BACKGROUND: Management of oral iron overdoses is well-established, but there is limited literature regarding intravenous iron sucrose overdoses. Indications for administering deferoxamine after oral iron overdoses include clinical signs and symptoms of toxicity, along with a serum iron concentration ≥ 500 µg/dL. Reported signs and symptoms of iron sucrose overdose do not appear to correlate with those of oral iron overdoses. CASE REPORT: We present a case of intravenous iron sucrose overdose in a clinically well-appearing patient with a presenting serum iron concentration that was several times higher than the usual threshold concentration for initiating deferoxamine treatment. A 21-year-old woman presented to the emergency department after an accidental intravenous iron sucrose overdose. The patient received a home infusion of 1000 mg iron sucrose, which was five times the prescribed dose. Her presenting serum iron concentration was 1799 µg/dL, with bicarbonate and anion gap both within normal limits and an unremarkable physical examination. Because she did not have evidence of severe iron toxicity, she was treated supportively and deferoxamine was not administered. Her serum iron concentration decreased below the toxic range over the next 14 h, and she was discharged home the next day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This patient was managed successfully with expectant care alone, suggesting that iron sucrose overdose has much lower toxicity than oral iron salt overdose. This discrepancy between measured iron concentrations and clinical presentation may be explained by the elimination kinetics of iron sucrose having separate redistribution and elimination phases.

Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial.

A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.

Intravenous iron sucrose is safe but does not prevent development of anemia or iron deficiency in healthy cats undergoing serial venipuncture.

OBJECTIVE: To evaluate IV iron sucrose safety and impact on hematologic and iron indices in healthy cats. ANIMALS: 5 healthy research cats. PROCEDURES: Cats were administered iron sucrose (0.5 mg/kg, IV) over 30 minutes. Monitoring for acute reactions (temperature, heart rate, respiratory rate, and blood pressure) was performed every 5 minutes during injection and every 15 minutes for an additional hour. Baseline, 24-hour, and 1-, 2-, and 3-week postinjection measurements of CBC with reticulocyte indices, iron panel (ferritin, total iron-binding capacity, and iron), calculated transferrin saturation (TSAT), and serum amyloid A (SAA) concentration were performed. RESULTS: No cat experienced an acute drug reaction. SAA concentration was increased at 24 hours versus baseline. TSAT and ferritin decreased over time, with 3 cats developing concurrent functional iron deficiency (FID) and anemia. Hct (Spearman correlation [rs] = 0.805), hemoglobin (rs = 0.770), and reticulocyte hemoglobin content (rs = 0.581) correlated with TSAT. CLINICAL RELEVANCE: IV iron sucrose was well tolerated in healthy cats but was associated with transient increase in the systemic inflammatory marker SAA. Efficacy evaluation of dose based on iron deficit is needed in sick cats. Despite cumulative blood draw volume below recommended limits, anemia and FID were observed, which has important implications for experimental designs and serial hematologic monitoring. Further evaluation of inflammatory response to IV iron sucrose administration is warranted.

Implementation of a protocol for management of antepartum iron deficiency anemia: a prospective cohort study.

BACKGROUND: In randomized trials, antepartum intravenous iron sucrose is effective at improving predelivery hemoglobin in iron deficiency anemia. Yet, there is a gap between this knowledge and its implementation into care. OBJECTIVE: We aimed to determine if the implementation of a standardized protocol for the management of antepartum anemia outside of a clinical trial improves intravenous iron sucrose utilization and clinical outcomes. STUDY DESIGN: We performed a prospective cohort study evaluating the incorporation of an anemia protocol into routine clinical care for women with antepartum hemoglobin <11.0 g/dL. Our protocol, developed with multidisciplinary stakeholders, included (1) serial third trimester hemoglobin assessment, (2) oral iron supplementation for antepartum hemoglobin 9.5-11 g/dL, and (3) antepartum intravenous iron sucrose use (300 mg weekly for 3 weeks) for hemoglobin <9.5 g/dL. We compared 6-months preimplementation (January 2018 to June 2018) to 6-months postimplementation (January 2019 to June 2019). The outcomes evaluated were antepartum intravenous iron sucrose utilization, the number of intravenous iron sucrose dosages, predelivery hemoglobin, and blood transfusion. RESULTS: A total of 1423 women were included (pre=778; post=645) without significant baseline differences. The antepartum hemoglobin nadir was no different between the groups (pre: 10.2; interquartile range [9.6-10.6] vs post: 10.2; interquartile range [9.6-10.6]; P=.77). The implementation of a standardized protocol for the management of antepartum anemia was associated with 80% increased odds of receiving intravenous iron sucrose than the preimplementation group (pre: 4.8% vs post: 8.2%, P=.008; odds ratio, 1.79; 95% confidence interval, [1.16-2.77]). The implementation of a standardized protocol for the management of antepartum iron deficiency anemia was also associated with higher hemoglobin at admission for delivery (pre: 10.9; interquartile range [10.1-11.6] vs post: 11.0; interquartile range [10.3-11.7], P=.048). There were no significant differences between the groups in blood product transfusion (pre: 7.1% vs post: 5.1%, P=.13). CONCLUSION: Implementation of a standardized antepartum anemia protocol is associated with increased intravenous iron sucrose utilization and improvement in predelivery hemoglobin.

Single-dose intravenous ferric carboxymaltose infusion versus multiple fractionated doses of intravenous iron sucrose in the treatment of post-operative anaemia in colorectal cancer patients: a randomised controlled trial.

BACKGROUND: Recent clinical guidelines suggest that treatment of postoperative anaemia in colorectal cancer surgery with intravenous iron reduces transfusion requirements and improves outcomes. The study aimed at comparing two intravenous iron regimens in anaemic patients after colorectal cancer surgery. MATERIALS AND METHODS: This was a single-centre, open-label, randomised, controlled trial in patients undergoing elective colorectal cancer surgery. Patients with moderate to severe anaemia (haemoglobin [Hb] <11 g/dL) after surgery were randomly assigned 1:1 to receive ferric carboxymaltose (FC; 1,000 mg, single dose) or iron sucrose (IS; 200 mg every 48 hours until covering the total iron deficit or discharge). Randomisation was stratified by Hb level: <10 g/dL (Group A) or ≥10-10.9 (Group B). The primary endpoint was the change in Hb concentration at postoperative day 30. Secondary endpoints included iron status parameters, transfusion requirements, complications, and length of hospital stay. RESULTS: From September 2015 to May 2018, 104 patients were randomised (FC 50, IS 54). The median intravenous iron dose was 1,000 mg and 600 mg in the FC and IS groups, respectively. There were no between-group differences in mean change in Hb from postoperative day 1 to postoperative day 30 (FC: 2.5 g/dL, 95% CI: 2.1-2.9; IS: 2.4 g/dL, 95% CI: 2.0-2.8; p=0.52), in transfusion requirements or length of stay. The infection rate was lower in the FC group compared with the IS group (9.8% vs 37.2%, respectively). DISCUSSION: The administration of approximately 500 mg of IS resulted in an increase in Hb at postoperative day 30 similar to that of 1,000 mg of FC, but it was associated with a higher infection rate. Future research will be needed to confirm the results, and to choose the best regime in terms of effectiveness and side effects to treat postoperative anaemia in colorectal cancer patients.

Efficacy and cost effectiveness of intravenous ferric carboxymaltose versus iron sucrose in adult patients with iron deficiency anaemia.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. OBJECTIVE: To determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. DATA SOURCES: Electronic medical record i.e. Cerner® system. TARGET POPULATION: Adults patients with iron deficiency anaemia. TIME HORIZON: A 12-month period (01/01/2018-31/12/2018). PERSPECTIVE: Hamad Medical Corporation (HMC, a public hospital). INTERVENTION: IV Ferric Carboxymaltose versus IV Iron Sucrose. OUTCOME MEASURES: With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. RESULTS OF BASE-CASE ANALYSIS: There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. RESULTS OF SENSITIVITY ANALYSIS: Not applicable. LIMITATIONS: The study did not consider the clinical or humanistic outcome. CONCLUSIONS: The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.

Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.

BACKGROUND: Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting. METHODS: We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822. FINDINGS: Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62-11·73; seven trials) and serum ferritin (mean difference 49·66 µg/L, 13·63-85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51-16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions. INTERPRETATION: Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment. FUNDING: None.

Safety and Efficacy of Intravenous Ferric Derisomaltose Compared to Iron Sucrose for Iron Deficiency Anemia in Patients with Chronic Kidney Disease With and Without Heart Failure.

Ferric derisomaltose (FDI) is an intravenous (IV) high-dose iron formulation approved in the US for the treatment of iron deficiency anemia in adults who are intolerant of/have had an unsatisfactory response to oral iron, or who have non-dialysis-dependent chronic kidney disease (NDD-CKD). FERWON-NEPHRO was a randomized, open-label, multicenter clinical trial evaluating the safety and efficacy of a single infusion of FDI 1,000 mg versus up to 5 doses of iron sucrose (IS) 200 mg (recommended cumulative dose, 1,000 mg) over 8 weeks in patients with NDD-CKD and iron deficiency anemia. Of 1,525 patients included in the safety analysis, 244 (16%) had a history of heart failure (HF). Overall, the rate of serious or severe hypersensitivity reactions was low and did not differ between treatment groups. Cardiovascular adverse events (AEs) were reported for 9.4% of patients who had HF and 4.2% who did not. Time to first cardiovascular AE was longer following administration of FDI compared with IS (hazard ratio: 0.59 [95% CI: 0.37, 0.92]; p=0.0185), a difference that was similar in patients with or without HF (p=0.908 for interaction). Patients achieved a faster hematological response (assessed by changes in hemoglobin and ferritin concentrations, and increase in transferrin saturation) with FDI versus IS. In conclusion, in patients with NDD-CKD, a single infusion of FDI was safe, well tolerated, and was associated with fewer cardiovascular AEs and a faster hematological response, compared to multiple doses of IS. These effects were similar for patients with and without HF.

Economic impact of ferric carboxymaltose in haemodialysis patients / Impatto economico dell'utilizzo di carbossimaltosio ferrico nei pazienti in emodialisi

Intravenous iron supplementation is essential in hemodialysis (HD) patients to recover blood loss and to meet the requirements for erythropoiesis and, in patients receiving erythropoietin, to avert the development of iron deficiency. In a recent real-world study, Hofman et al. showed that a therapeutic shift from iron sucrose (IS) to ferric carboxymaltose (FCM) in HD patients improves iron parameters while reducing use of iron and erythropoietin. The objective of this economic analysis is to compare the weekly cost of treatment of FCM vs IS in hemodialysis patients in Italy. The consumption of drugs (iron and erythropoietin) was derived from Hofman's data, while the value was calculated at Italian ex-factory prices. The analysis was carried on the total patient sample and in two subgroups: patients with iron deficiency and patients anemic at baseline. In addition, specific sensitivity analyses considered prices currently applied at the regional level, simulating the use of IS vs iron gluconate (FG) and epoetin beta vs epoetin alfa. In the base-case analysis, the switch to FCM generates savings of -€12.47 per patient/week (-21%) in all patients, and even greater savings in the subgroups with iron deficiency -€17.28 (-27%) and in anemic patients -€23.08 (-32%). Sensitivity analyses were always favorable to FCM and confirmed the robustness of the analysis. FCM may represent a cost-saving option for the NHS, and Italian real-world studies are needed to quantify the real consumption of resources in dialysis patients.

Conversion of haemodialysis patients from iron sucrose to iron isomaltoside: a real-world experience.

BACKGROUND: Anaemia is common in haemodialysis (HD) patients and associated with significant morbidity and mortality. Intravenous (IV) iron combined with erythropoiesis-stimulating agents (ESA) is the mainstay treatment of anaemia in these patients. The comparative efficacy and risk of adverse events with IV iron preparations have been assessed in only a few trials. METHODS: This was a retrospective observational study in 2 centres designed to compare the safety and efficacy of iron sucrose (IS-Venofer®) versus iron isomaltoside (IIM-Diafer®) in haemodialysis patients. The study included patients currently on dialysis and receiving Venofer who were switched to Diafer® and monitored for at least 12 months for each iron preparation. RESULTS: A total of 190 patients were included and had a mean age of 65.8 years (SD ± 15.5). Non-inferiority was confirmed with no change in mean haemoglobin per mg of iron administered over a 12-month period. In total there were 41,295 prescriptions of iron isomaltoside and 14,685 of iron sucrose with no difference in the number of reported adverse events during the study period (7 each, none were severe). There was a statistically significant effect on Hb over time after conversion, including adjustment for multiple comparisons. There were significant improvements in ferritin over time, which remained at 6 months (P < 0.01). The weekly iron dose was similar after adjustment (P = 0.02). The EPO dose did not differ significantly after month 0 in patients switched to IIM. CONCLUSIONS: This study demonstrates the comparative safety and efficacy of iron isomaltoside versus iron sucrose, with similar dosing schedules in dialysis patients. Iron isomaltoside is non-inferior to iron sucrose in maintaining Hb in patients on regular haemodialysis/haemodiafiltration with no difference in the number of reported adverse events.

Trends in Anemia, Iron, Therapy, and Transfusion in Hospitalized Pediatric Patients with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate trends in diagnosis and management of iron deficiency anemia using a large national children's hospital database in pediatric patients admitted with inflammatory bowel disease (IBD). STUDY DESIGN: In this retrospective multicenter cohort study, we used the Pediatric Health Information System de-identified administrative database. Patients age <21 years with ≥2 admissions with International Classification of Disease, Ninth Revision and Tenth Revision codes for Crohn's disease or ulcerative colitis from 2012 to 2018 were included. We extracted data regarding diagnoses of anemia and/or iron deficiency, and receipt of oral iron, intravenous (IV) iron, and/or blood transfusion. Data were analyzed descriptively. RESULTS: We identified 8007 unique patients meeting study criteria for a total of 28 260 admissions. The median age at admission was 15.4 years. A diagnosis of anemia was documented in 29.8% of admissions and iron studies were performed in 12.6%. IV iron was given in 6.3% of admissions and blood transfusions in 7.4%. The prevalence of the diagnosis of anemia among IBD admissions increased from 24.6% in 2012 to 32.4% in 2018 (P < .0001). There was a steady increase in the proportion of IBD admissions that used IV iron, from 3.5% in 2012 to 10.4% in 2018 (P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% (P < .0001). CONCLUSIONS: Iron deficiency anemia is prevalent among pediatric patients with IBD admitted to US children's hospitals. From 2012 to 2018, there was an increase in the use of inpatient IV iron for the treatment of iron deficiency anemia and a decrease in transfusions.

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency.

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer®), a nanomedicine that has been used clinically since 1949. Treatment with iron sucrose is particularly beneficial owing to its ability to rapidly increase hemoglobin, ferritin, and transferrin saturation levels, with an acceptable safety profile. Recently, important new data relating to the use of iron sucrose, including the findings from the landmark PIVOTAL trial in patients with end-stage kidney disease, have been reported. Several years ago, a number of iron sucrose similars became available, although there have been concerns about the clinical appropriateness of substituting the original iron sucrose with an iron sucrose similar because of differences in efficacy and safety. This is a result of the complex and unique physicochemical properties of nanomedicines such as iron sucrose, which make copying the molecule difficult and problematic. In this review, we summarize the evidence accumulated during 70 years of clinical experience with iron sucrose in terms of efficacy, safety, and cost-effectiveness.