Ferric derisomaltose 1g/10ml solution for injection vials

AbstractBackgroundIntravenous iron is the preferred treatment for patients with iron deficiency anemia in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions (HSRs) and, rarely, anaphylactic or anaphylactoid reactions.AimThe objective of the present study was to systematically review the literature to identify and analyze data on the incidence of HSRs after administration of ferric derisomaltose (FDI) or ferric carboxymaltose (FCM).MethodA prospectively-registered systematic literature review was conducted to identify prospective randomized controlled trials comparing FDI and FCM with other intravenous iron formulations or oral iron. Searches were conducted in PubMed (including MEDLINE), EMBASE, and the Cochrane Library in November 2020. The relative incidence of serious or severe HSRs occurring on the day or day after dosing of intravenous iron, recorded under the standardized Medical Dictionary for Regulatory Activities query for anaphylactic reaction.ResultsData were obtained from seven randomized controlled trials of FCM (N = 2683) and ten of FDI (N = 3474) enrolling 10,467 patients in total. The number of patients experiencing any serious or severe HSR event was 29/2683 (1.08%) with FCM versus 5/3474 with FDI (0.14%). Bayesian inference of proportions showed the event rates to be significantly lower with FDI relative to FCM.ConclusionHSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM. Further large-scale, head-to-head trials of the iron formulations would be required to confirm this finding.

Abstract licence: CC BY 4.0

BackgroundSince 2015, ferric carboxymaltose (FCM), an intravenous (IV) iron formulation used for treating iron deficiency anemia (IDA), has been associated with an increasing number of reported hypophosphatemia (HPP) cases. Information on HPP clinical manifestations and incidence has not been reviewed.MethodsWe reviewed HPP-associated adverse events reported to the FDA, case reports, case series, observational databases, clinical trials, meta-analyses, and FDA-approved labels. Our analysis found that FCM-associated HPP is a clinically important adverse drug reaction (ADR). The most common clinical manifestations are general weakness, fatigue, bone pain, muscle pain, osteomalacia, and fractures. Information on rates of FCM-associated HPP was from a review of clinical trials, observational databases, systematic reviews, and meta-analyses.ResultsClinical trials comparing FCM with other IV iron preparations identified FCM-associated HPP rates between 50% and 92% versus 2% and 8% with other IV iron formulations. Meta-analyses and systematic reviews confirmed these numbers. FDA-approved FCM labels do not include details of available ADR information in case reports, case series, observational databases, randomized trials, and meta-analyses.ConclusionWe conclude that although the FDA-approved FCM Prescribing Label was updated in 2023, more robust recommendations on FCM-associated HPP are needed to prevent negative outcomes including osteomalacia and fractures. For patient safety, FCM label should advise monitoring serum phosphate levels prior to initiating first doses and before subsequent doses for all patients. Given differences between the FDA-approved FCM label and data reviewed herein, clinicians must be educated about FCM-associated HPP, difficulties treating HPP cases, and should consider administering other IV iron formulations that have lower rates of HPP.

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Background/Objectives: Iron-deficiency anemia (IDA) is a common extraintestinal complication of inflammatory bowel disease (IBD). Among high-dose intravenous (IV) iron options, ferric carboxymaltose (FCM) carries a higher risk of treatment-emergent hypophosphatemia than ferric derisomaltose (FDI), with potential clinical consequences. Slovenia's healthcare setting, characterized by very low IV iron infusion tariffs and recent pricing in which FCM is substantially less expensive than FDI, warrants a setting-specific cost effectiveness evaluation. Methods: We integrated two methodological components: (i) a payer-perspective cost-effectiveness analysis using a patient-level microsimulation model with (ii) an umbrella review of systematic reviews and a targeted search of expert consensus statements on IV-iron-associated hypophosphatemia. Results: In the base case, FDI required fewer infusions than FCM (11.1 vs. 14.2 over 10 years) but generated only €95 in IV iron administration savings due to low tariffs, while drug procurement was €1166 higher with FDI than FCM. When incorporating the clinical impact of hypophosphatemia, incremental quality-adjusted life years (QALYs) were 0.136, yielding an incremental cost-effectiveness ratio (ICER) of €6590/QALY. The umbrella review consistently showed higher hypophosphatemia incidence with FCM (up to 92%) compared with other IV iron formulations (Conclusions: Despite Slovenia's low IV iron infusion tariffs and lower FCM price, FDI remained cost-effective in this model, largely due to its more favorable hypophosphatemia profile within the model. These findings suggest that hypophosphatemia risk should be considered when selecting IV iron therapy in routine IBD care.

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Iron-deficiency anemia is the most common hematologic disorder in pregnancy. Slow iron repletion, poor gastrointestinal tolerance, and late presentation during gestation often limit the effectiveness of oral ferrous salts, which remain the traditional first-line treatment. Intravenous iron offers faster iron delivery, but its role in routine antenatal care remains uncertain, particularly regarding its long-term safety and cost-effectiveness compared to traditional oral iron treatments. This qualitative systematic review included 10 randomized controlled trials published within the last decade that enrolled pregnant women with iron-deficiency anemia or persistent iron deficiency (defined, where applicable, as ferritin <30 μg/L after approximately four weeks of oral iron therapy) and compared intravenous iron with oral iron or one intravenous formulation with another. Across the included trials, intravenous iron generally produced more rapid ferritin replenishment and, in many studies, a faster rise in hemoglobin than oral therapy. Oral ferrous preparations were associated with more gastrointestinal adverse effects; for example, in one study, gastrointestinal treatment-related events were reported in more women receiving oral ferrous sulfate versus those receiving ferric carboxymaltose. In another trial, nausea/vomiting occurred in greater number of oral-iron recipients versus intravenous ones, while constipation and epigastric discomfort were reported only in the oral group. By contrast, serious intravenous treatment-related events were uncommon in the larger trials.​ ​Smaller and medium-sized trials generally favored parenteral iron for hematologic recovery, but the largest pragmatic studies from India, Malawi, and Nigeria showed that biochemical superiority did not consistently translate into lower rates of late-pregnancy anemia or improved major maternal and neonatal outcomes. One head-to-head intravenous trial also suggested practical and hematologic advantages of ferric carboxymaltose over iron sucrose. From a hematology perspective, intravenous iron appears most useful when rapid restoration of iron stores is needed, when adherence to oral therapy is doubtful, or when little time remains before delivery. Future trials should standardize ferritin-based diagnostic criteria, clearly distinguish hematologic from obstetric endpoints, and better define which patients are most likely to derive clinically meaningful benefit from parenteral iron.

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Iron deficiency (ID) is a common and clinically significant comorbidity in patients with heart failure (HF), contributing to reduced exercise capacity, poor quality of life, and increased hospitalization risk. Although intravenous (IV) iron therapy has demonstrated efficacy in improving functional outcomes, the comparative effectiveness of IV vs. oral (per os, or PO) iron supplementation remains uncertain. We conducted a systematic review and network meta-analysis (NMA) of 13 randomized controlled trials (RCTs) evaluating IV iron (ferric carboxymaltose, ferric derisomaltose, iron sucrose), PO iron (ferrous sulfate, ferrous fumarate, polysaccharide, sucrosomial, ferric polymaltose), and placebo in HF patients with ID, analyzed as route-specific class effects. Outcomes analyzed included six-minute walk distance (6MWD), ferritin, transferrin saturation (TSAT), HF hospitalization, all-cause mortality, and cardiovascular (CV) mortality. We used a Hartung-Knapp random-effects framework with Sidik-Jonkman variance, assessed heterogeneity and inconsistency using I2, τ2, design-by-treatment interaction, and node-splitting. Risk of bias was assessed independently by two reviewers using Risk of Bias 2 (RoB 2), and certainty of evidence for all outcomes was graded using GRADE adapted for NMA. Because most contrasts included fewer than 10 RCTs, formal tests for publication bias were not feasible, and potential small-study effects were considered qualitatively in the GRADE assessments. Trials that reported outcomes only as medians and interquartile ranges (IQRs), or baseline values without follow-up data, were excluded from quantitative pooling and described narratively. IV iron significantly improved 6MWD compared to placebo (mean difference (MD) +26.0 m; 95% confidence interval (CI): 18.1 to 33.9), increased ferritin (MD +237.2 μg/L), and reduced the risk of HF hospitalization (risk ratio (RR) 0.79; 95% CI: 0.66 to 0.93), with moderate to high certainty. PO iron showed a comparable, but not statistically significant, mean improvement in 6MWD (MD +35.1 m; 95% CI: -5.2 to +75.4), with wider CIs and inconsistent ferritin and TSAT gains. Neither IV nor PO iron was associated with a significant reduction in all-cause or CV mortality, although a trend toward benefit was observed with IV therapy. Numerical SUCRA values favored IV iron for HF hospitalization (77.9 vs. 57.6 for PO, 14.5 for placebo), ferritin (100.0 vs. 50.0 vs. 0.0), and TSAT (74.0 vs. 75.8 vs. 0.2), while PO iron ranked slightly higher for 6MWD (76.3 vs. 73.7 vs. 0.0). Included PO formulations encompassed both traditional preparations (ferrous sulfate/fumarate, polysaccharide) and newer agents such as sucrosomial iron and ferric polymaltose. Adverse events were comparable across groups: IV iron was not associated with excess mortality or serious adverse events, and PO iron was primarily limited by gastrointestinal intolerance. Sensitivity analyses restricting outcomes to trials with 3-12 months of follow-up showed consistent results, while longer studies mainly influenced event counts rather than the direction of effect. Our findings support the use of IV iron as the preferred strategy to improve symptoms and reduce hospitalizations in HF patients with ID, whereas PO iron may be considered when IV therapy is inaccessible. Further large-scale trials are needed to clarify long-term mortality impact and the role of newer PO formulations.

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Ulcerative colitis and Crohn's disease, two types of inflammatory bowel disease (IBD), often cause anemia, primarily due to iron deficiency and chronic inflammation. Anemia negatively affects patients' daily functioning and quality of life, causing symptoms including headaches, exhaustion, and dyspnea. In IBD, iron deficiency arises from reduced intake, chronic blood loss, and impaired absorption. While oral iron supplements are commonly used, their poor absorption and gastrointestinal side effects limit their effectiveness, especially in IBD patients. The European Crohn's and Colitis Organization (ECCO) recommends intravenous iron, such as ferric carboxymaltose (FCM), as iron deficiency anemia in IBD can be managed using a safe and efficient substitute. With regard to treating iron deficiency anemia in patients with IBD, the purpose of this study is to investigate the safety and effectiveness of intravenous ferric carboxymaltose. We conducted a thorough search of medical databases, such as the Cochrane library, PubMed, and ResearchGate, to gather relevant literature. Using the databases, we found a total of 297 relevant articles. The identified studies have been screened, eligibility criteria have been introduced, and 14 research studies were selected for inclusion. This review adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, with quality assessments conducted using the Cochrane risk of bias 2 scale for randomized tests and the Newcastle-Ottawa scale for observational examination. We reviewed 14 research articles involving 2,493 patients. Among these, five were randomized controlled trials (RCTs), and the remaining nine were observational studies. The primary outcomes assessed were the therapeutic response (defined as hemoglobin ≥2 g/dL rise or normalization, improvement in iron profile parameters) and any adverse effects after FCM is administered to IBD patients. FCM was found to be highly effective in improving hemoglobin and iron profile parameters, with a generally good safety profile. Ferric carboxymaltose was the most efficient and well-tolerated intravenous (IV) iron formulation, proving safer and more effective than other iron therapies in patients suffering from IBD. However, severe hypophosphatemia can lead to serious complications, including heart failure, pulmonary failure, rhabdomyolysis, fractures, and osteomalacia, which may worsen its long-term impact. Therefore, the risk of hypophosphatemia associated with prolonged FCM use requires careful monitoring and further research to ensure its long-term safety and assess its effects on patients' quality of life.

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Abstract Introduction For heart failure (HF) with iron deficiency (ID), the benefits of intravenous iron might differ according to kidney function. Methods IRONMAN was a randomised, open-label trial of intravenous ferric derisomaltose (FDI) versus usual care (UC) in patients with HF, left ventricular ejection fraction ≤45%, and ID (transferrin saturation <20% and/or ferritin <100 µg/L). The primary composite endpoint of recurrent hospitalisation for HF and cardiovascular (CV) death was lower in those assigned to FDI. Analysis according to baseline estimated glomerular filtration rate (eGFR) is now reported, with outcomes assessed in 3 categories of eGFR. Results Of 1,137 patients randomised, eGFR was <45 mL/min/1.73 m2 for 435 (38%), 45–59 mL/min/1.73 m2 for 295 (26%), and ≥60 mL/min/1.73 m2 for 407 (36%). Patients with eGFR <45 mL/min/1.73 m2 were older and had more severe HF and more events. For the primary outcome, the primary endpoint rates per 100 patient-years for FDI versus UC across eGFR categories were 164 and 213 (rate ratio [RR]: 0.77 [95% CI: 0.57, 1.03]), 84 and 105 (RR: 0.79 [95% CI: 0.51, 1.22]), 88 and 93 (RR: 0.98 [95% CI: 0.62, 1.54]), respectively, but no statistically significant interaction between eGFR category and treatment effect was observed (pinteraction = 0.67). When eGFR was <45 mL/min/1.73 m2, FDI was associated with more favourable effects on Minnesota Living with Heart Failure score at 4 months (p < 0.001; pinteraction = 0.01 by eGFR class) and trends to greater reductions in first hospitalisation for HF or CV death (hazard ratio [HR]: 0.76 [95% CI: 0.58, 0.99]; pinteraction = 0.53) and first hospitalisation for myocardial infarction, stroke or HF, or CV death (HR: 0.71 [95% CI: 0.55, 0.92]; pinteraction = 0.29), although tests for interaction by eGFR class were not significant. Conclusion For patients with HF and ID, those with eGFR <45 mL/min/1.73 m2 are more symptomatic, have worse outcomes, and might receive greater benefit from FDI. Analysis of other randomised trials, ideally an individual patient data meta-analysis, are required to confirm these findings.

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Abstract Background Iron deficiency affects nearly half of patients with heart failure with reduced ejection fraction and is associated with impaired functional capacity, recurrent hospitalizations, and increased mortality. Intravenous iron therapy improves exercise tolerance, but the comparative effectiveness of different formulations remains uncertain. Objectives To compare the efficacy of ferric carboxymaltose, ferric derisomaltose, and iron sucrose in patients with heart failure with reduced ejection fraction and iron deficiency using a network meta-analysis. Methods We systematically searched PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science through August 2025 for randomized controlled trials of intravenous ferric carboxymaltose, ferric derisomaltose, or iron sucrose versus placebo. Fifteen randomized controlled trials published between 2007 and 2025 enrolling 7,761 patients were included. The primary outcomes were hospitalization for heart failure, all-cause mortality, and cardiovascular mortality. Secondary outcomes included change in six-minute walk distance, serum ferritin, and transferrin saturation. A frequentist random-effects network meta-analysis was performed, and treatment rankings were assessed using surface under the cumulative ranking curve probabilities. Results Twelve trials reported hospitalization for heart failure, showing significant reduction with ferric carboxymaltose (risk ratio 0.80, 95% confidence interval 0.69–0.92) and nonsignificant trends with ferric derisomaltose (0.80, 0.61–1.04) and iron sucrose (0.41, 0.15–1.07). No formulation reduced all-cause or cardiovascular mortality. Functional capacity improved with all formulations (mean difference +21.1 to +54.0 meters versus placebo), though heterogeneity was high. Ferritin and transferrin saturation increased significantly across all formulations, with the largest ferritin gain from ferric derisomaltose (+329 µg/L) and the most consistent transferrin saturation improvement from ferric carboxymaltose (+7.1%). Conclusions In patients with heart failure with reduced ejection fraction and iron deficiency, intravenous iron therapy—particularly ferric carboxymaltose—reduces hospitalization for heart failure, improves functional capacity, and corrects iron indices. Mortality benefits remain uncertain. These findings support guideline-endorsed use of intravenous iron, with ferric carboxymaltose as the best-studied option, while further outcome data for ferric derisomaltose and iron sucrose are needed.

Abstract licence: CC BY 4.0