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Objective: This study investigates the safety and efficacy of ferric derisomaltose (FDI) and its effect on blood transfusion requirements in women with severe anaemia secondary to heavy menstrual bleeding (HMB). Methods: Medical records of women aged =18 years who were admitted to Tuen Mun Hospital with severe iron deficiency anaemia (a haemoglobin level of <8.0 g/dL and a mean corpuscular volume of <80 fL) secondary to HMB in the periods before (1 July 2014 to 30 June 2018) and after (1 July 2018 to 30 June 2022) the introduction of FDI were retrospectively reviewed. Results: In total, 1373 and 983 patients were admitted before and after the introduction of FDI, respectively. The mean number of blood units transfused per patient decreased from the pre-FDI period to the post-FDI period (2.02 vs 1.19, p<0.001). The decrease remained significant after adjusting for age, ethnicity, baseline haemoglobin, and leiomyoma. In 384 patients who received FDI, 55 (14.3%) had a hypersensitivity reaction (HSR), 41 of which were mild. There were no cases of cardiac or respiratory arrest or allergic reaction necessitating adrenaline administration. The occurrence of an HSR was not associated with the number of known drug allergies (p=0.076), ethnicity (p=0.563), or age (p=0.06). After FDI administration, the mean haemoglobin level increased from 6.2 g/dL to 10.6 g/dL (p<0.001), whereas the mean ferritin increased from 22.5 µg/L to 149 µg/L (p<0.001) at 3 to 4 weeks. Conclusion: Intravenous FDI is safe and effective for treating severe iron deficiency anaemia secondary to HMB. FDI significantly reduces the requirement for blood transfusions. 14.3% of patients had an HSR. FDI mitigates the burden on blood transfusion services and supports patient blood management principles. [ABSTRACT FROM AUTHOR]

[Display omitted] The complex nature of intravenous (IV) iron formulations makes manufacturing and characterising similars challenging. This study examined whether simple in vitro tests can distinguish the high-dose IV iron formulation, Monofer® (ferric derisomaltose [FDI]), from the first intended copies of FDI, Rapifer® (FDI intended similar A [FDIIS-A]) and Tosiron® (FDI intended similar B [FDIIS-B]), approved in India and Pakistan, respectively. Neither intended similar is available in Europe or the United States. Iron content, pH, density, non-volatile residue, carbohydrate content, molecular weight distribution, complex robustness (measured using acid hydrolysis half-life [t ½ ]) and free (dialysable) iron content were examined. Mean results from three batches of FDIIS-A were compared with mean values calculated from three batches of Monofer®. Due to product withdrawal, only one batch of FDIIS-B was available for comparison with Monofer®. Iron content was similar for all formulations (∼100 mg/mL). The chromatograms (obtained using gel permeation chromatography) of FDIIS-A and FDIIS-B differed from that of Monofer®. FDIIS-A was substantially less robust than Monofer® (t ½ : 15 h versus 40.3 h); t ½ for FDIIS-B was not tested. Free iron content was substantially higher in FDIIS-A (0.091 % w/v) and FDIIS-B (1.0 % w/v) versus Monofer® (<0.003 % w/v). Where tested, remaining parameters varied between the formulations (insufficient sample quantities prevented all tests being conducted for all intended similars). For all tests, greater inter-batch variability was seen for FDIIS-A versus Monofer®. Simple in vitro tests demonstrated that, aside from total iron content, the first intended similars of FDI bear little resemblance to their originator drug. It is clear that the efficacy and safety profile of Monofer® cannot be extrapolated to the two intended similars. The results call for increased regulatory scrutiny of intended IV iron similars. [ABSTRACT FROM AUTHOR]

Abstract Background Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients. Methods This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators’ discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions. Results The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg. Conclusions The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study. Trial registration ClinicalTrials.gov NCT02546154 , 10 September 2015.

Hyeok Jun Goh,1 Ki Soo Lee,1 Tae Hyo Kim,1 Kyu Nam Kim,2 Hyun Jin Lim,2 Kyu Shik Kim,3 Won Jae Yang,4 Jung Ki Jo3 1Department of Urology, Dong-A University, College of Medicine, Busan, Korea; 2Department of Anesthesia and Pain Medicine, Hanyang University, College of Medicine, Seoul, Korea; 3Department of Urology, Hanyang University, College of Medicine, Seoul, Korea; 4Department of Urology, Soonchunghyang University Hospital, Seoul, KoreaCorrespondence: Jung Ki JoDepartment of Urology, Hanyang University, College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, KoreaTel +821025196241Email victorjo38@hanyang.ac.krPurpose: Postoperative anemia is associated with increased morbidity and mortality in patients undergoing surgery. Anemia is also a common feature during sepsis. Therefore, here, we aimed to investigate the safety and efficacy of intravenous iron isomaltoside 1000 (Monofer®) in patients undergoing elective urologic surgery and in those with urosepsis.Materials and Methods: This multicenter study was conducted through the review of the medical records of patients with postoperative anemia undergoing elective urologic surgery or with urosepsis in a multicenter hospital. Patients received a single intravenous iron isomaltoside (IIM), and their hemoglobin (Hb) level was evaluated before and after administration of IIM. Safety data included adverse effects and hypersensitivity reactions. In addition, the patients were divided into three groups (200 mg, 400 mg, and 600 mg IIM) to compare Hb changes before and after the administration of IIM.Results: The study analyzed 52 men and 30 women with a mean age of 67 years. There was a significant difference between pre-treatment Hb and post-treatment Hb according to the type of the surgery after administration (p=0.01) of IIM in patients with postoperative anemia, and the mean preoperative Hb before IIM administration was 8.5 g/dL and that after IIM administration was 9.9 g/dL (p=0.006) in patients with urosepsis. The mean preoperative Hb changed from 10 g/dL to 11 g/dL after administration (p< 0.001) of IIM in the whole cohort. There were no side effects due to the administration of intravenous IIM.Conclusion: A single perioperative intravenous injection of IIM 1000 significantly increased the Hb level in patients with anemia who underwent urologic elective surgery. Moreover, this treatment can be considered to have potential clinical benefits for anemia caused by sepsis.Keywords: anemia, iron, iron isomaltoside 1000, urosepsis

Background: Postpartum anaemia adversely affects maternal mood, cognition, and maternal-infant interactions. Intravenous iron isomaltoside is effective and safe for non-pregnant patients with iron deficiency anaemia, but data on its use in Hong Kong women during peripartum period are limited. This study aims to determine the effectiveness and safety of iron isomaltoside (Monofer) in women with postpartum haemorrhage or anaemic symptoms. Methods: Records of women who received iron isomaltoside (Monofer) when haemoglobin (Hb) level was <7g/dL (or ≥7g/dL when concomitant with anaemic symptoms) irrespective of mode of delivery between April 2018 and March 2021 were reviewed. Primary outcome measures included response to iron isomaltoside treatment (measured by pre- and post-treatment Hb levels), resolution of anaemic symptoms, and the number and types of adverse reactions related to treatment. Secondary outcome measures included associations between patient characteristics and Hb response. Results: 126 women were included for analysis. Most were nulliparous, delivered vaginally, and had minor postpartum haemorrhage. Most had a baseline Hb level of <10.0 (mean, 7.36) g/dL, but only 53.2% of them had anaemic symptoms. No women experienced serious adverse events. Only four (3.2%) women had mild adverse events of rash (n=3) or pruritis (n=1). At the 6-week follow-up, the mean Hb level increased 4.39 g/dL to 11.8 g/dL (p<0.001), with only one woman reporting anaemic symptoms. 12 (9.5%) of 126 women had some form of haemoglobinopathy (usually thalassemia trait) and had lower Hb levels even before pregnancy. Compared with women with normal Hb pattern, women with haemoglobinopathy had lower post-treatment Hb responses (p=0.001). Hb response was positively associated with delivery blood loss (r=0.188) and negatively associated with baseline Hb level (r= -0.279). Conclusion: Iron isomaltoside (Monofer) is effective and safe for postpartum anaemia. It enables rapid improvement in Hb level and anaemic symptoms, even for those with haemoglobinopathy. [ABSTRACT FROM AUTHOR]

Abstract Background Iron deficiency is common in pregnancy. If left untreated, iron deficiency can lead to iron deficiency anaemia, which is a condition related to maternal and neonatal morbidity. The prevalence of iron deficiency increases through the trimesters, which means that women with iron deficiency in the beginning of pregnancy also have a great risk of developing iron deficiency anaemia during pregnancy. Standard treatment is oral iron in individualised intensified doses based on screening values in 1st trimester. Maternal symptoms of iron deficiency and iron deficiency anaemia include fatigue, reduced physical performance, and restless legs syndrome (RLS). Severe anaemia may cause dizziness, dyspnea, palpitation, orthostatism, and syncope, and it decreases the woman’s ability to cope with blood loss during delivery. The anaemia may also compromise contractility in the uterine musculature increasing the risk for prolonged labour, caesarean section, and postpartum haemorrhage. Foetal iron deficiency may cause low birthweight and adversely affect foetal and early childhood brain development with long-term deficits. Methods In this randomised comparative, open-label, single-centre, phase IV trial, 200 pregnant women between 14 and 21 weeks of gestation who have iron deficiency after 4 weeks of standard treatment will be randomised 1:1 to either a single 1000 mg dose of intravenously administered ferric derisomaltose/iron isomaltoside 1000 or a fixed dose of 100 mg oral ferrous fumarate containing 60 mg ascorbic acid. The primary endpoint is to prevent iron deficiency anaemia defined by a low level of haemoglobin throughout the trial. Other endpoints include other haematological indices of iron deficiency and anaemia, clinical outcomes by questionnaires, and collection of adverse events. Explorative endpoints by medical record follow-up include complications up to 7 days after delivery. Discussion This trial will provide evidence on how to prevent iron deficiency anaemia. The trial population represents a clinical reality where pregnant women often have sustained iron deficiency despite an increased oral iron dose. Thus, this evidence can be used to consider the optimal 2nd line of treatment in iron-deficient pregnant women. Trial registration European Union Drug Regulating Authorities Clinical Trials Database 2017-000776-29. Registered on 3 May 2017. ClinicalTrials.gov NCT03188445 . Registered on 15 June 2017.