Ferric Carboxymaltose Administration Research Articles

Iron deficiency therapy in pregnant women: advantages and new possibilities of iron carboxymaltose

Introduction. Impact of iron deficiency on pregnancy outcomes appears an urgent issue despite generally accepted standards of therapy. Iron needs increase during pregnancy and manifestations of its deficiency reduce QoL in pregnant women and worsen newborn health. Ferric carboxymaltose helps overcome iron deficiency in a quick and efficient manner from the 2nd trimester.Aim. To analyse the results of ferric carboxymaltose therapy of iron deficiency conditions in pregnant women.Materials and methods. In this article we presented our own experience in providing ferric carboxymaltose therapy to treat iron deficiency in 152 pregnant women from the 2nd trimester.Results and discussion. Correction of anaemic syndrome was observed in more than 73.3% (up to 93.3% depending on the severity of primary anaemia) as early as the first week after administration of ferric carboxymaltose. Haemoglobin and ferritin levels at 3 week post-infusion were significantly higher than pre-infusion levels (p < 0.001). Improvement of haemoglobin levels at 6 weeks after initiation of therapy was achieved in all women with mild anaemia and in 98.5% of women with severe anaemia. No definite severe hypersensitivity reactions were detected. The overall incidence of side effects was 10.5%, with headache being the most frequently reported type (7.9%). All pregnancies resulted in a live birth without malformations; the rate of preterm birth was 9.5%.Conclusion. Ferric carboxymaltose is an effective drug to quickly correct iron deficiency in pregnant women with a minimum number of adverse reactions and without negative impact on newborn health.

Severe Hypophosphatemia After Ferric Carboxymaltose Infusion: A Case Report

Ferric carboxymaltose (FCM) allows for rapid and total correction of iron deficiency with a lower risk of hypersensitivity reactions compared to other IV iron preparations. However, FCM is associated with potentially serious adverse events, including hypophosphatemia, following the infusion. The mechanism behind FCM-induced hypophosphatemia is not well understood, but pre-existing risk factors can increase the likelihood of severe and persistent hypophosphatemia. We report a clinical case of a male patient who developed severe hypophosphatemia (1.0 mg/dL) after administration of FCM for the treatment of post-cardiotomy normocytic anemia. He required hospital admission and 16 weeks of phosphorous supplementation.

The differential effect of modern intravenous iron on fibroblast growth factor 23 and phosphate in non-dialysis dependent CKD – the exploratory randomized controlled double-blind ExplorIRON-CKD study

BackgroundIntravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover.MethodsThe single-center double-blind randomized controlled trial “Iron and Phosphaturia – ExplorIRON-CKD” primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1–2 days following iron administration, 2 weeks, 1 month (second iron administration), 1–2 days following second administration, 2 months and 3 months following initial infusion.ResultsTwenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1–2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1–203.1) %; p < 0.001 and Baseline to 1–2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 – 25.4) % vs. FCM: 235.1 (138.5–434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI.ConclusionsThe study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds.Trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019–004370-26 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB) (First date of trial registration: 03/12/2019).

P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in Finland

Abstract Background Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland. Methods A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects. Results Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention. Conclusion Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.

Safety and Efficacy of FCM in the Management of Iron Deficiency Anaemia: a Multi-centre Cohort-based Study

This study investigated the efficacy and safety of ferric carboxymaltose (FCM) in the treatment of iron deficiency anaemia (IDA) in a cohort of 100 patients across four locations in West Bengal, India. The results demonstrated significant improvements in various hematological parameters, including a substantial increase in haemoglobin levels, following FCM administration. The study also highlighted the absence of adverse events, showcasing a favorable safety profile of FCM in this population. The use of FCM, a third-generation parenteral iron formulation, proved effective in addressing moderate-to-severe IDA, aligning with existing evidence supporting its efficacy and safety. The rapid and substantial improvement in haemoglobin levels observed within four weeks of FCM administration emphasizes its efficiency in iron repletion, particularly in cases where oral preparations may be insufficient. The absence of adverse effects further supports the tolerability of FCM, a crucial factor in its consideration for widespread use. The study contributes valuable real-world data, especially in the context of the high prevalence of anaemia in India. The findings underscore the potential of FCM as a cornerstone in the treatment of severe anaemia, advocating for its inclusion in targeted interventions and public health initiatives. Overall, this study adds to the growing body of evidence supporting FCM as a promising option in the management of iron deficiency anaemia.

Heart failure: update of the ESC 2023 guidelines

The 2023 update of the European Society of Cardiology (ESC) guidelines recommends (classIA) the administration of sodium-glucose transporter 2inhibitors (SGLT2i) also for patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced EF (HFmrEF). Thus, SGLT2i are the only medication that should be given to all heart failure patients for improvement of prognosis independent of left ventricular EF. The rapid administration of the fantastic four drugs and their prompt titration after aheart failure decompensation is now included in the guidelines with a class IB recommendation. For patients with reduced EF (HFrEF) or HFmrEF and iron deficiency there is now a class IIa recommendation for intravenous administration of ferric carboxymaltose or ferric derisomaltose.

Trends of phosphorus levels after intravenous administration of ferric carboxymaltose

Abstract Background Iron deficiency and anaemia are present in a large number of patients with heart failure. Intravenously ferric carboxymaltose (FCM) is the recommended treatment, but it may be associated with hypersensitivity reaction and hypophosphatemia, the later mainly in subjects with normal renal function. The prevalence of hypophosphatemia driven by FCM in patients with heart failure (HF) is not well established. Purpose To assess the prevalence and trends of serum phosphorus levels after FCM administration in outpatients with HF. Methods Prospective, observational, consecutive, and descriptive study of patients admitted in a HF clinic eligible to receive FCM between January 2022 and June 2022. Phosphorus and calcium homeostasis regulators (magnesium, vitamin D, parathyroid hormone, alkaline phosphatase) were drawn at baseline and after 3 weeks of the infusion. In those patients with documented hypophosphatemia after iron administration, a third measurement was performed at three months from baseline. Paired T-test was used to compare mean values and logistic regression to predict relationship of changes in serum phosphorus with other factors. Results 101 patients were included (71.5 ± 10.6 years, 31.7% women, LVEF 43.9 ±11.9%, 49.5% of ischaemic aetiology, glomerular filtration rate 39.44 ±10 mL/min/m2). Mean baseline phosphorous was 3.64 ± 0.66 mg/dL, declining to 2.74 ±0.88 mg/dL (p for trend = 0.001). Calcium, magnesium, and vitamin D also showed a post-infusion declining tendency (p = 0.001, p = 0.05 and p= 0.002, respectively), whereas PTH significantly increased (p = 0.015). At three weeks, 38 (37.6%) patients had phosphorous levels below the normal threshold (mean 2.15 ± 0.76 mg/dl), which normalized at three months from baseline (mean 3.12 ±0.77 mg/dl; p = 0.71) without specific treatment. Figure 1 shows phosphorus dynamics of the 38 patients with infusion hypophosphatemia. There was no predicted correlation between FCM dose, glomerular filtration rate and phosphorous trends (p = 0.627, P = 0.234 respectively). No clinical adverse event was reported. Conclusion Ferric carboxymaltose infusion in patients with HF is associated with a decline in circulating phosphorous, with 1 in 3 patients showing frank hypophosphatemia. This effect is transient and does not require treatment nor active phosphorus monitoring.Trends of hypophosphatemia

Iron deficiency in myocardial ischaemia: molecular mechanisms and therapeutic perspectives.

Systemic iron deficiency (SID), even in the absence of anaemia, worsens the prognosis and increases mortality in heart failure (HF). Recent clinical-epidemiological studies, however, have shown that a myocardial iron deficiency (MID) is frequently present in cases of severe HF, even in the absence of SID and without anaemia. In addition, experimental studies have shown a poor correlation between the state of systemic and myocardial iron. MID in animal models leads to severe mitochondrial dysfunction, alterations of mitophagy, and mitochondrial biogenesis, with profound alterations in cardiac mechanics and the occurrence of a fatal cardiomyopathy, all effects prevented by intravenous administration of iron. This shifts the focus to the myocardial state of iron, in the absence of anaemia, as an important factor in prognostic worsening and mortality in HF. There is now epidemiological evidence that SID worsens prognosis and mortality also in patients with acute and chronic coronary heart disease and experimental evidence that MID aggravates acute myocardial ischaemia as well as post-ischaemic remodelling. Intravenous administration of ferric carboxymaltose (FCM) or ferric dextrane improves post-ischaemic adverse remodelling. We here review such evidence, propose that MID worsens ischaemia/reperfusion injury, and discuss possible molecular mechanisms, such as chronic hyperactivation of HIF1-α, exacerbation of cytosolic and mitochondrial calcium overload, amplified increase of mitochondrial [NADH]/[NAD+] ratio, and depletion of energy status and NAD+ content with inhibition of sirtuin 1-3 activity. Such evidence now portrays iron metabolism as a core factor not only in HF but also in myocardial ischaemia.

Ferric Carboxymaltose in Patients with Acute Decompensated Heart Failure and Iron Deficiency: A Real-Life Study.

Background: The correction of iron deficiency (ID) with ferric carboxymaltose (FCM) is a recommended intervention in heart failure (HF) with reduced ejection fraction. Our aim is to evaluate, in a real-life setting, the clinical significance of ID screening and FCM treatment in acute decompensated HF (ADHF). Methods: In a cohort of ADHF patients, the prevalence of ID and FCM administration were investigated. Among the 104 patients admitted for ADHF, in n = 90 (median age 84, 53.5% with preserved left ventricular ejection fraction-LVEF), a complete iron status evaluation was obtained. ID was detected in n = 73 (81.1%), 55 of whom were treated with in-hospital FCM. The target dose was reached in n = 13. Results: No significant differences were detected in terms of age, sex, comorbidities, or LVEF between the FCM-supplemented and -unsupplemented patients. During a median follow-up of 427 days (IQR 405-466) among the FCM-supplemented patients, only 14.5% received FCM after discharge; the mortality and rehospitalizations among FCM-supplemented and -unsupplemented patients were similar (p = ns). In a follow-up evaluation, ID was still present in 75.0% of the FCM-supplemented patients and in 69.2% of the unsupplemented patients (p = ns). Conclusions: In this real-life ADHF cohort, FCM was administered at lower-than-prescribed doses, thus having no impact on ID correction. The significance of our findings is that only achieving the target dose of FCM and pursuing outpatient treatment can correct ID and produce long-term clinical benefits.

Iron deficiency in cardiac surgery patients and the possibility of its correction at the preoperative stage

Among cardio-surgical patients, the prevalence of iron deficiency conditions reaches 70 %, and anemia is detected in less than 50% cases. Meanwhile, both anemia and latent iron deficiency are risk factors for adverse outcomes in cardio-surgical patients. These conditions are associated with a high frequency and greater volume of blood transfusions as well as with a longer stay in the hospital. Timely diagnosis and correction of iron deficiency, regardless of the presence of anemia, are mandatory at the stage of preoperative preparation. The use of oral iron medicines is limited by their low efficacy in this category of patients and a high risk of adverse events. Intravenous iron medicines have a high potential for correcting iron deficiency, and their efficacy and safety have been previously demonstrated. Administration of ferric carboxymaltose has proved beneficial in studies on iron deficiency correction in cardiological and cardio-surgical patients. In these patients, ferric carboxymaltose improved the dynamics of ferritin and hemoglobin, reduced the risk of blood transfusion, and decreased the duration of stay in the hospital. Preoperative intravenous administration of ferric carboxymaltose to cardio-surgical patients can improve clinical outcomes and the cost effectiveness of cardiac surgery.

Ferric carboxymaltose for patients with heart failure in all-range ejection fraction

Introduction and objectivesIron deficiency (ID) is common in heart failure (HF) patients and is linked to exercise impairment, worse quality of life, and HF hospitalisation. Clinical practice guidelines recommend checking and correcting ID with ferric carboxymaltose (FCM). However, there is a lack of evidence in patients with left ventricular ejection fraction (LVEF) >40%. MethodsWe included all HF outpatients treated with FCM after ID diagnosis (ferritin <100ng/mL or ferritin 100–299ng/mL and transferrin saturation <20%). We analysed clinical and analytical parameters before FCM administration and at 3 months according to LVEF: preserved (>50%), mildly reduced (41–49%), and reduced (<40%). ResultsWe included 235 patients (51.5% female) aged 73.5±10.7 years. Ninety-six patients have reduced LVEF (40.8%), 41 mildly reduced (17.4%), and 98 preserved (41.7%). Patients with preserved LVEF have more anaemia (42.6% vs 26.8% vs 52.6%; P=.02). Less than 50% of patients received the correct dose of FCM, especially patients with preserved LVEF (P=.004). One patient (0.4%) presented a local exanthema with no other adverse effects. At 3 months, all analytical parameters significantly improved, except haemoglobin (12.9 vs 13.0mg/dL; P=.95) and natriuretic peptides (3261 vs 3471pg/mL; P=.56) in mildly reduced LVEF patients. The functional class did not improve in preserved LVEF patients, but it did in the rest. ConclusionsFCM is safe and effective in correcting ID in HF patients regardless of LVEF. Natriuretic peptides are reduced in all patients except those with mildly reduced LVEF. Functional class improvement is less likely in patients with preserved LVEF.

Incidence and predictors of hypophosphataemia after ferric carboxymaltose use-A 3-year experience from a single institution in Singapore.

Ferric carboxymaltose (FCM) administration helps reduce transfusion requirements in the perioperative situation, which improves patient outcomes and reduces healthcare costs. However, there is increasing evidence of hypophosphataemia after FCM use. We aim to determine the incidence of hypophosphataemia after FCM administration and elucidate potential biochemical factors associated with the development of subsequent hypophosphataemia. A retrospective review of anonymised data of all FCM administrations in a single institution was conducted from August 2018 to August 2021. Each unique FCM dose administered was examined to assess its effect on Hb and serum phosphate levels within the subsequent 28 days from each FCM administration. Phosphate levels were repeatedly measured within the 28-day interval and the lowest phosphate level within that period was determined. Patients' serum phosphate levels within 28 days of FCM administration were compared against normal serum phosphate levels within 2 weeks before FCM administration. The odds ratios of various pre-FCM serum markers were calculated to elucidate potential biochemical predictors of post-FCM hypophosphataemia. In 3 years, a total of 1296 doses of FCM were administered to 1069 patients. The mean improvement in Hb was 2.45 g/dL (SD = 1.94) within 28 days of FCM administration, with the mean time taken to peak Hb levels being 6.3 days (SD = 8.63), which is earlier than expected, but was observed in this study and hence reported. The incidence of hypophosphataemia <0.8 mmol/L was 22.7% (n = 186), and <0.4 mmol/L was 1.6% (n = 9). This figure is lower than the numbers reported in previously published meta-analyses given that routine checks of serum phosphate levels were not conducted initially and hence could possibly be higher. The odds of developing hypophosphataemia (<0.8 mmol/L) were 27.7 (CI: 17.3-44.2, p < 0.0001) if baseline serum phosphate was less than 1 mmol/L. The odds of developing hypophosphataemia (<0.8 mmol/L) were 1.3 (CI: 1.08-1.59, p < 0.01) if the change in Hb levels observed after FCM administration were more than 4 g/dL. Hypophosphataemia after FCM administration is significant and FCM should be used by clinicians with caution.

Benefits of Ferric Carboxymaltose Administration for Enhanced Hemoglobin Levels in Urban Population of Sindh: BOFERIN® Observational Study

Abstract: Background: Iron deficiency anemia is a major public health issue in developing countries, especially among women of reproductive age. Anemia is a major public health problem in women of reproductive age in rural Pakistan and a large proportion of women were found to have low levels of serum iron. Materials and Methods: A multicenter observational cohort study was conducted at Karachi &amp; Hyderabad from 8th February 2022 to 30th April 2022. Women with low hemoglobin level and age 18-45 years were included in this study. Patients were grouped according to 1-week assessment and 3-week assessment of hemoglobin concentration. A single dose of a generic substituent ferric carboxymaltose (Boferin®) was administered to the patients over 15 minutes infusion. Baseline hemoglobin levels were compared at 1 week and 3 weeks after administration of Ferric Carboxymaltose. Results: A total of 104 patients were enrolled in this study. The mean hemoglobin levels at baseline were 9.22 ± 0.175 g/dl and 7.55 ± 0.329 g/ dl for 1-week and 3-week, respectively. The mean hemoglobin increases after 1 week and 3 week was reported as 1.4211± 0.169 g/dl (p&lt; 0.001) and 2.321± 0.335 g/dl (p&lt; 0.001) respectively. Only three patients presented with mild to moderate adverse effect which included abdominal discomfort and nausea. Conclusion: This is a first in class study has shown statistically significant increase in hemoglobin at 1-week and 3-week interval with minimal side effects. It is concluded that Boferin® is efficacious in increasing hemoglobin levels in patients with iron deficiency anemia with its safety being documented in pregnant Pakistani population as well.

Is the Benefit of Treating Iron Deficiency Greater in Acute Heart Failure with Renal Dysfunction?

This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction. A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5). There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19-0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14-0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17-0.55; p: 0.237). The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Iron therapy and severe arrhythmias in HFrEF: rationale, study design, and baseline results of the RESAFE-HF trial.

The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE-HF) registry study aims to provide real-word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). The RESAFE-HF (NCT04974021) study was designed as a prospective, single-centre, and open-label registry study with baseline, 3, 6, and 12month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron-related endpoint of haemoglobin≥12g/dL, ferritin≥50ng/L, and transferrin saturation>20%. Secondary endpoints include unplanned HF-related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant-19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. The RESAFE-HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real-world data. Special focus will be given on the arrhythmic burden post-FCM administration.

Efficacy of ferric carboxymaltose in iron deficiency anemia patients scheduled for pancreaticoduodenectomy.

Perioperative transfusion is reported to be an independent risk factor not only for postoperative complications but also for early recurrence of periampullary carcinoma after pancreaticoduodenectomy (PD). The purpose of this study was to evaluate the safety and efficacy of ferric carboxymaltose (FCM) in reducing the need for perioperative transfusion in iron deficiency anemia patients scheduled for PD. Twenty-two male patients (hemoglobin [Hb] 7 to <13 g/dL) and 18 female patients (Hb 7 to <12 g/dL) were enrolled in the study group and administered FCM 1-3 weeks before PD. The perioperative transfusion rate was the primary endpoint; morbidity, length of postoperative hospital stay, change in hematological parameters after FCM injection, and adverse effects of FCM were also investigated. The perioperative transfusion rate of the study group was 22.5% (9 of 40). Hb level was significantly higher on the day of the operation compared to baseline (P < 0.001). Levels of Hb, transferrin saturation, and ferritin were higher at the follow-up compared to baseline (P = 0.008, P = 0.033, and P < 0.001, respectively). FCM administration was associated with a reduced need for perioperative transfusion and can safely stabilize hematological parameters.

Comparative study on intravenous iron sucrose versus intravenous ferric carboxymaltose in the management of iron deficiency anaemia in pregnancy in a tertiary care hospital, Bengaluru

Background: Iron deficiency is the most common nutritional deficiency worldwide; it affects 1.6 billion people Iron deficiency (ID) and iron deficiency anemia (IDA) are often encountered in the general population, particularly among children and women with abnormal uterine bleeding (AUB) and during pregnancy as well as postpartum period Intravenous (IV) iron replacement can deliver the total amount of required iron over a short period. Currently, the most commonly used IV iron formulations are iron sucrose (IS) and ferric carboxymaltose (FCM) [4-6]. Iron sucrose does not require test dose and is safe. Ferric carboxymaltose (FCM) is the latest I.V. iron formulation which can be used at high doses and allows rapid administration (up to 1000 mg in a single dose infused in 15 minutes) The present study was a comparative study of parenteral iron therapy (intravenous iron sucrose versus intravenous ferric carboxymaltose in the management of iron deficiency anaemia in pregnancy.Methods: In the present study, 50 pregnant women with IDA were randomly distributed into two groups of 25 each. Group - A: 25 receiving intravenous iron sucrose therapy; Group - B: 25 receiving intravenous ferric carboxymaltose therapy.Results: Majority of the study participants in Group A had gestational age between 20–25 weeks (48%). The mean age of the study participants in Group A was found to be 22.86+4.42 weeks. Majority of the study participants in Group B had gestational age between 20-25 weeks (36%). The mean age of the study participants was found to be 23.01+3.01 weeks. Majority of the study participants in Group A had nil parity (40%). 36% of the study participants in Group B had nil parity. 60% of the study participants in group A had Mild degree of anaemia with 52% in group B having mild degree of anaemia. 40% and 44% of the study participants in group A and group B had Moderate degree of anaemia respectively. The association was found to be statistically significant between the mean Hb and Ferritin values pre-treatment, 3rd and 6th week follow-up post treatment and the 2 groups of study participants. The adverse effects were comparatively lower among Group B (IV ferric carboxymaltose) than Group A (IV iron sucrose) of the study participants.Conclusions: IV ferric carboxymaltose administration increases the hemoglobin level more rapidly as compared to iron sucrose in women with iron deficiency anemia in the pregnancy. It also stores iron more rapidly. No serious adverse effects were recorded. Ferric carboxymaltose is well tolerated, safe and effective alternative to iron sucrose in iron deficiency anemia of pregnancy. FCM has the advantage of a large dose administration per sitting and early rise in hemoglobin level.

Incidence, evolution and risk factors of hypophosphatemia in patients with solid tumors receiving ferric carboxymaltose: a retrospective cohort study

ABSTRACT Objectives Ferric carboxymaltose (FCM) is increasingly used in the management of cancer-related anemia, yet it may cause hypophosphatemia. This retrospective study describes the incidence, evolution and risk factors of hypophosphatemia in a cohort of patients with solid tumors receiving FCM. Methods Serum phosphorus concentration was assessed longitudinally using a random intercepts model. The probability of developing hypophosphatemia, as graded by CTCAE version 4.0, was investigated using a multi-state model. Transition hazards were modeled non-parametrically and semi-parametrically by a Cox model. Causal marginal risk differences between baseline interventions on serum phosphorus and/or FCM dose were obtained via G-computation. Results In 174 ambulatory patients with solid tumors receiving FCM at two university hospitals between October 2020 and September 2021, the risk of developing moderate-to-severe hypophosphatemia was 36.0% (95% confidence interval (CI) 28.2–43.9%) and peaked within 16 days after first FCM administration. The average duration of moderate-to-severe hypophosphatemia was 12.4 days. After adjustment for confounders, lower baseline serum phosphorus (adjusted hazard ratio (aHR) 0.88 per 0.1 mmol/L increase, 95% CI 0.79–0.98) and higher FCM dose (first dose: aHR 1.12 per 1 mg/kg increase, 95% CI 1.01–1.25; second dose: aHR 1.06 per 1 mg/kg increase, 95% CI 1.00–1.13) significantly increased the hazard of moderate-to-severe hypophosphatemia. Conclusion Approximately one out of three ambulatory patients with solid tumors may develop moderate-to-severe hypophosphatemia after FCM administration. Baseline serum phosphorus and FCM dose may be modifiable risk factors that should be considered for intervention in order to mitigate the risk of hypophosphatemia.

Modern Intravenous Iron Therapy: A Review on Safety and Practical Aspects

Introduction: Intravenous iron formulations have been approved in Europe and North America for the treatment of iron deficiency if oral iron is not tolerated or not efficacious. Recently-developed intravenous iron formulations exhibit specific physicochemical and immunological properties, with distinct bioavailability, efficacy and safety profiles. Area of Interest: intravenous iron formulations safety and tolerability were reviewed in the framework of a Swiss expert meeting. This work focused on the specificity of each compound with emphasis on the practical aspects of its use. Expert Opinion: Adverse reactions in response to iv formulations can be categorized into two main types: hypophosphataemia and hypersensitivity. Hypophosphatemia follows administration of ferric carboxymaltose at a higher rate in comparison to other formulations, but is mostly mild, transient and asymptomatic. However, the decrease in serum phosphate following repeated administration of iron preparations can affect bone health, particularly in patients at risk for osteomalacia. Severe hypersensitivity reactions are the most lifethreatening adverse reactions to intravenous iron supplementation. Iron (III)- isomaltoside 1000 seems to induce severe hypersensitivity more often (RR 5.6 - 16.2) than ferric carboxymaltose. Further studies are needed to address issues of long-term safety in high dose and prolonged administration of intravenous iron preparations in case of chronic diseases.

Randomised Controlled Trial of Intravenous Iron (ferric carboxymaltose) for Second Trimester Anaemia in Malawian Pregnant Women (REVAMP)

Introduction Anemia affects 46% of pregnancies in Africa. WHO estimates 50% of anaemia in pregnancy (44% in Africa) is responsive to iron; other causes of anaemia in Africa include infection (e.g. P. falciparum). Antenatal oral iron supplementation improves maternal anaemia and birthweight, but adherence may be suboptimal. Ferric carboxymaltose (FCM) is a modern intravenous iron formulation which enables provision of 1000mg (or 20mg/kg) in one 15 minute infusion. We reasoned FCM is an option to treat antenatal anaemia in low income primary-care settings, but the feasibility, efficacy and safety of this approach is unproven. Methods REVAMP was an open label, individually randomised controlled trial set in Malawi, sub-Saharan Africa, a low income setting where anaemia, malaria and other infections (including HIV) are common. Women were screened at antenatal clinics and were eligible if they met criteria including capillary haemoglobin (Hb) <10.0g/dL, negative Plasmodium rapid diagnostic test, and ultrasound-confirmed singleton pregnancy of 13 to 26 weeks gestation. HIV positivity was not an exclusion. Women were randomly assigned 1:1 to the intervention arm (FCM 20mg/kg, up to 1000mg, once at enrolment) or standard of care (SOC, 60mg elemental iron b.d for 90 days, in alignment with local practice). All women received IPTp with Suphadoxine-Pyrimethamine at enrolment and 28 days. The primary maternal outcome was anaemia at 36 weeks gestation. Secondary maternal outcomes included anaemia at other timepoints (28 days post infusion, during delivery and 28 days post-partum), and Hb, iron deficiency (ID) and iron deficiency anaemia (IDA) at each timepoint. The primary neonatal outcome was birthweight. Subgroup analyses (e.g. by baseline anaemia severity, ID, IDA, HIV status) were prespecified. Safety outcomes included incidence of adverse events (AEs) during infusion, and all AEs from randomisation to 4 weeks postpartum, including serious AEs (SAEs): unplanned hospitalisation or death including pregnancy loss and neonatal death. Results We screened 21258 women and randomised 862. Baseline characteristics, including anaemia severity and prevalence of iron deficiency, inflammation, and HIV were similar between arms. Compared with SOC, FCM reduced the prevalence of anaemia at 28 days post infusion (PR 0.91 95% CI 0.85 to 0.97, P=0.007) but did not statistically significantly decrease anaemia prevalence at the primary timepoint of 36 weeks gestation (52.5% vs 56.8%, prevalence ratio (PR) 0.92, 95% CI 0.81 to 1.06, P=0.27), or at delivery or 28 days postpartum (Table 1). Hb concentrations increased from baseline to 28 days post partum in both arms and were greater in women randomised to FCM 28 days post infusion (1.3 vs 1.1 g/dL, difference 0.19 [0.06-0.33]) and at 28 days postpartum (3.1 vs 2.9 g/dL, difference 0.25 [0.06-0.45]). IDA prevalence was reduced at each timepoint, including at 36 weeks gestation (PR 0.29 [0.20 to 0.43], P<0.001). ID prevalence was also reduced at all timepoints. Birthweight did not differ between FCM and SOC. Adverse reactions during FCM administration were reported by 26/430 (6.0%) women; there were no infusion-related SAEs. There was no clinically relevant difference in AEs by any systemic organ class, including infection (including malaria), and SAEs in women and neonates (Table 2). Hypophosphataemia (PO4<0.080mmol/L) at 28 days post infusion was seen in 22/403 (5.5%) women randomised to FCM compared to 8/382 (2.0%) with SOC. There was no difference in pregnancy loss or stillbirth between arms. Conclusions In this low-income, malaria endemic setting, treatment of anaemic pregnant women in the second trimester with FCM worked faster than SOC to resolve anaemia but benefit was not evident by 36 weeks. However FCM reduced ID and IDA at every timepoint. Administration of FCM was feasible and safe. Extended follow-up of mothers and babies is underway. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal