Efficacy of iron isomaltoside among anemic females of Bundelkhand region: An interventional study

Anupma Upadhyay; Syed Esam Mahmood; Meena Saxena; Kanchan Singh

doi:10.4103/ijas.ijas_4_18

ORIGINAL ARTICLE

Year : 2017 | Volume : 2 | Issue : 2 | Page : 45-48

Efficacy of iron isomaltoside among anemic females of Bundelkhand region: An interventional study

Anupma Upadhyay¹, Syed Esam Mahmood², Meena Saxena¹, Kanchan Singh¹
¹ Department of Obstetrics and Gynaecology, Government Medical College, Banda, Uttar Pradesh, India
² Department of Community Medicine, Integral Institute of Medical Sciences and Research, Lucknow, Uttar Pradesh, India

Date of Submission	25-May-2018
Date of Acceptance	15-Jul-2018
Date of Web Publication	30-Aug-2018

Correspondence Address:
Dr. Syed Esam Mahmood
Department of Community Medicine, Integral Institute of Medical Sciences and Research, Lucknow, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijas.ijas_4_18

Abstract

Introduction: More than a quarter of the world's population is anemic with about one half of the burden from iron deficiency. The prevention and treatment of iron deficiency is a major public health goal especially in women in low-income countries. Challenges in the treatment of iron deficiency include a selection of an iron replacement product that can be given as high-dose intravenous (IV) infusion in single visit with good safety profile. In this pilot study, a new IV therapeutic agent iron isomaltoside 1000 with above-desired properties was investigated to establish its efficacy in the treatment of iron deficiency anemia (IDA).
Material and Methods: This 3 months' prospective interventional hospital-based study was conducted on 42 nonpregnant women with moderate-to-severe anemia attending obstetrics and Gynecology Department at Government Medical College Banda in Bundelkhand region. Pre- and post-hemoglobin (Hb) estimation after 3 weeks of a single shot of iron isomaltoside 1000 IV infusion was done. A rise in Hb of 2 g/dl or more at 21 days was considered a satisfactory response. SPSS software 17.0 version was used for data analysis.
Results: Mean preinfusion Hb was found to be 7.139 g/dl and mean postinfusion Hb was found to be 10.088 g/dl. Thus, a rise of 2.949 g/dl in mean Hb after 3 weeks was recorded after a single infusion of iron isomaltoside among the anemic females.
Conclusion: Iron isomaltoside has demonstrated robust efficacy in patients suffering from IDA due to different etiologies. The wide dosing range allows iron correction in a single visit with minimal risk of anaphylaxis and is thus cost-effective for health-care system.

Keywords: Anemia, Bundelkhand region, iron isomaltoside

How to cite this article:
Upadhyay A, Mahmood SE, Saxena M, Singh K. Efficacy of iron isomaltoside among anemic females of Bundelkhand region: An interventional study. Imam J Appl Sci 2017;2:45-8

How to cite this URL:
Upadhyay A, Mahmood SE, Saxena M, Singh K. Efficacy of iron isomaltoside among anemic females of Bundelkhand region: An interventional study. Imam J Appl Sci [serial online] 2017 [cited 2023 May 31];2:45-8. Available from: https://www.e-ijas.org/text.asp?2017/2/2/45/240163

Introduction

Iron is an essential element as it plays an important role in many vital biological processes such as the synthesis of heme which forms the basis of hemoglobin (Hb) the oxygen-carrying protein of the blood, the formation of myoglobin, energy metabolism, neurotransmitter production, the formation of collagen, and immune system function.^[1],[2] The lack of iron is one of the principal causes of anemia in the general population. It is, therefore, not surprising that iron deficiency anemia (IDA) is associated with increased morbidity and mortality.^[2],[3]

Treatment with oral iron supplements is simple, inexpensive, and a relatively effective way of treating iron deficiency conditions but is not an ideal treatment mainly due to their gastrointestinal adverse effects (particularly when using ferrous iron compounds), poor duodenal absorption due to concomitant gastrointestinal pathologies (inflammatory bowel disease or any other cause of chronic inflammation, malignancy), and the long course of treatment needed to resolve anemia (1–2 months) and replenish body iron stores (another 3–6 months). Noncompliance to a prescribed course of oral iron is common, and even in compliant patients, poor intestinal absorption fails to compensate for the iron need in the presence of ongoing blood losses or inflammatory conditions.^[4],[5],[6]

Treatment with intravenous (IV) iron is clearly superior to oral iron and presents several advantages such as faster and higher increase in Hb levels and replenishment of body iron stores. For these reasons, modern formulations of IV iron have emerged as safe and effective alternatives for IDA management.^{[7],[8],[9],[10],[11]} The main clinical indications for IV iron treatment are intolerance to oral iron or noncompliance to an oral regimen, in acquired or hereditary decreased intestinal iron absorption (intestinal malabsorption syndromes), in cases with severe IDA (Hb <7 g/dL) because of continuous or uncontrolled blood loss and/or increased iron needs and in cases of functional iron deficiency (anemia of chronic kidney disease (CKD), inflammatory diseases, and anemia of cancer). The usual benchmark for successful iron supplementation is a 2 g/dL increase in the Hb level in 3 weeks.^[12] The newest IV iron agent iron isomaltoside 1000 has a special matrix-like structure with 10 iron molecules per one isomaltoside pentamer in a strongly bound structure that enables a controlled and slow release of bioavailable iron with little risk of free iron toxicity.^[13] This allows iron isomaltoside 1000 to be administered safely as a rapid high-dose IV infusion offering considerable dose flexibility including the possibility of providing full iron repletion in a single infusion the so-called one dose iron repletion. In recent trials, a review of the safety of IV iron preparations, particularly in patients with CKD, by Kalra and Bhandari concluded that high-molecular weight iron dextrans are associated with increased risks, so their use for IV therapy should be avoided. The second- and third-generation IV irons are considered equally efficacious in treating iron deficiency in equivalent doses, but iron isomaltoside seems to have a lower frequency of serious and severe hypersensitivity reactions.^[14] With this background, this study was undertaken to establish the efficacy of iron isomaltoside in correcting IDA in nonpregnant anemic women in District Banda.

Materials and Methods

This pilot study was conducted on 42 nonpregnant women with moderate-to-severe anemia according to the World Health Organization criteria attending outpatient department and inpatient department of obstetrics and Gynecology Department at Government Medical College Banda in Bundelkhand region for 3 months in 2017. Searches were undertaken to provide insight into high-dose IV iron administration which included papers reporting studies undertaken with the new preparation, dosing parameters, and product specification from the manufacturer's summaries of product characteristics were inspected so that comment could be made on the appropriateness of the formulation for use. The protocol was approved by the Institutional Ethical Committee. Written informed consent was obtained from all participants.

Inclusion criteria

Women >18 years with moderate-to-severe but well-compensated IDA caused by different etiologies were recruited.

Exclusion criteria

Pregnancy, age <18 years, any hematological disorder other than IDA, known hypersensitivity, and resistance to injectable iron compounds, severe anemia in decompensated state requiring blood transfusion and anemia due to acute blood loss, i.e., postpartum hemorrhage (PPH). After inclusion in the study detailed history of each patient was taken including age, medical history, obstetrical history, menstrual history, family history, and history of intolerance or unresponsiveness to oral iron therapy. The detailed physical examination was carried out. Complete blood count (CBC) was done on peripheral venous blood collected from cubital vein by CBC cell counter (MEDONIC M SERIES, 3 PART). The 1000 mg infusion was diluted in 100 ml 0.9% normal saline and given over approximately 15 min. During the study, other iron supplementations (except from diet) were withheld. All patients were followed, and CBC repeated 3 weeks after therapy and rise in hematological parameters noted. A rise in Hb of 2 g/dl or more at 21 days was considered a satisfactory response. SPSS software 17.0 version (IBM, United States) was used for data analysis.

Results

Mean preinfusion Hb was found to be 7.139 g/dl and mean postinfusion Hb was found to be 10.088 g/dl. Thus, a rise of 2.949 g/dl in mean Hb in 3 weeks was recorded after a single infusion of iron isomaltoside among the anemic females [Figure 1] and [Figure 2].

Figure 1: Scatter diagram showing mean preinfusion hemoglobin levels. X-axis denotes numbers of patients and Y-axis denotes preinfusion hemoglobin levels

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Figure 2: Scatter diagram showing mean postinfusion hemoglobin levels. X-axis denotes number of patients and Y-axis denotes postinfusion hemoglobin levels

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Out of the 41 nonpregnant anemic females included in this study, majority were from rural background, (61%) and belonged to lower socioeconomic status (56.1%). A higher percentage of the anemic females was married (90.2%) and was aged above 30 years (48.8%). A higher proportion of the anemic women had parity <3 [Table 1].

Table 1: Sociodemographic characteristics (n=41)

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Discussion

The objective of this study was to evaluate the efficacy of iron isomaltoside in nonpregnant patients with IDA of Bundelkhand region. Iron isomaltoside induced significant increase (2.949 g/dl) in mean Hb level by single infusion within 3 weeks in this study. Isomaltoside 1000, the carbohydrate component in iron isomaltoside 1000, has a mean molecular weight of 1000 Da and consists predominantly of 3–5 glucose units. The carbohydrate isomaltoside is linear and unbranched with a low immunogenic potential. Iron isomaltoside 1000 has strongly bound iron within the iron isomaltoside formulation, which enables a controlled slow release of bioavailable iron to the iron-binding proteins with minimal risk of free iron toxicity.^[15]

Holm et al.^[16] conducted a randomized controlled trial later presented at the XXI FIGO world congress 2015^[17] to compare the efficacy of an IV high single dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with PPH. The primary outcome was the aggregated change in physical fatigue within 12 weeks' postpartum, which showed a statistical difference in favor of iron isomaltoside. This is in support to our study results. Wikström et al.^[18] investigated safety profile and efficacy of iron isomaltoside in CKD patients and concluded that iron isomaltoside administered to CKD patients as repeated bolus injections or single high-dose infusion was well tolerated and resulted in improved markers of iron status and anemia. This is again in agreement to our study results. Another open-label randomized clinical trial conducted in CKD patients by Kalra et al.^[19] compared IV iron isomaltoside to oral iron sulfate in reducing renal-related anemia, and concluded that Iron isomaltoside was noninferior to iron sulfate in increasing Hb from baseline to week 4 (P< 0.001). The study by Kalra et al.^[19] is again in favor of our study findings. Similar encouraging results have also been reported using this new IV iron for treating IDA in Inflammatory Bowel Disease patients by Reinisch et al.^[20] In another trial by Dermana et al. patients with IDA were randomized 2:1 to either iron isomaltoside or iron sucrose and significantly more IDA patients experienced hematologic response with iron isomaltoside and had a faster response than iron sucrose when treating a broad range of underlying causes of IDA.^[21] This is again in agreement with our study. The majority of the nonpregnant anemic females included in this study were from rural background and belonged to lower socioeconomic status. This can be attributed to the fact that rural females belonging to low socioeconomic status usually have nutritional anemia due to low dietary intake of iron, folic acid, and Vitamin B₁₂, poor bioavailability of iron in phytate-rich Indian diet and chronic blood loss due to infections such as malaria and hookworm. A higher percentage of the anemic females was married and was aged above 30 years in this study. This can be related to multiple conceptions and blood loss during menstruation. Inadequate iron, folic acid supplementation during pregnancy, is another possible reason for anemia among them. A higher proportion of the anemic women had parity <3. This may be because of small sample size included in this study. Further studies with bigger sample size are required.

Conclusion

The recognition of the high prevalence of IDA and its association with wide range of clinical situations, highlight the growing need for an IV iron preparation that should ideally be capable of delivering a wide dosing range to allow iron correction in a single or low number of visits, a rapid infusion and minimal potential side effects including low labile iron release and minimal risk of anaphylaxis. Furthermore, they should be convenient for the patient and the health-care professional and cost-effective. Iron isomaltoside fulfills these requirements and has been shown to be effective in treating IDA across multiple therapeutic groups. It has a low immunogenic potential, and it is use does not appear to be associated with clinically significant hypophosphatemia and is not constrained by the aluminum or sodium content in its formulation. Thus, we recommend further large population-based studies to be undertaken to establish iron isomaltoside as high dose, single visit iron repletion therapeutic agent. This will further strengthen the National Health Policy to formulate effective plans to combat this public health problem.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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