Ferric derisomaltose 100mg/2ml solution for injection ampoules

BACKGROUND: Intravenous 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. AIM: The 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). METHOD: A 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. RESULTS: Data 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. CONCLUSION: HSR 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

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.

Abstract licence: CC BY

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.

Abstract licence: CC BY

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.

Abstract licence: CC BY