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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 2  |  Issue : 2  |  Page : 45-48

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


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 Submission25-May-2018
Date of Acceptance15-Jul-2018
Date of Web Publication30-Aug-2018

Correspondence Address:
Dr. Syed Esam Mahmood
Department of Community Medicine, Integral Institute of Medical Sciences and Research, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijas.ijas_4_18

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  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 2018 Sep 20];2:45-8. Available from: http://www.e-ijas.org/text.asp?2017/2/2/45/240163




  Introduction Top


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 Top


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 Top


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 Top


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 Top


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.



 
  References Top

1.
Muñoz M, Villar I, García-Erce JA. An update on iron physiology. World J Gastroenterol 2009;15:4617-26.  Back to cited text no. 1
    
2.
Hersko C. Prevalence and causes of iron deficiency anaemia. In: Beaumont C, Beris P, Beuzard Y, Brugnara C, editors. Disorders of Iron Homeostasis, Erythrocytes, Erythropoiesis. Paris: European School of Haematology; 2006. p. 409-19.  Back to cited text no. 2
    
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Auerbach M, Ballard H. Clinical use of intravenous iron: Administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program 2010;2010:338-47.  Back to cited text no. 3
    
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Brugnara C, Beris P. Iron therapy. In: Beaumont C, Beris P, Beuzard Y, Brugnara C, editors. Disorders of Erythropoiesis, Erythrocytes and Iron Metabolism. Paris: European School of Haematology; 2009. p. 512-28.  Back to cited text no. 4
    
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Gisbert JP, Gomollón F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol 2008;103:1299-307.  Back to cited text no. 5
    
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Cook JD. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol 2005;18:319-32.  Back to cited text no. 6
    
7.
Muñoz M, Gómez-Ramírez S, García-Erce JA. Intravenous iron in inflammatory bowel disease. World J Gastroenterol 2009;15:4666-74.  Back to cited text no. 7
    
8.
Erichsen K, Ulvik RJ, Nysaeter G, Johansen J, Ostborg J, Berstad A, et al. Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scand J Gastroenterol 2005;40:1058-65.  Back to cited text no. 8
    
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Gasche C, Waldhoer T, Feichtenschlager T, Male C, Mayer A, Mittermaier C, et al. Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia. Am J Gastroenterol 2001;96:2382-7. Erratum: Am J Gastroenterol 2001;96:2296-8.  Back to cited text no. 9
    
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Schröder O, Mickisch O, Seidler U, de Weerth A, Dignass AU, Herfarth H, et al. Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease – A randomized, controlled, open-label, multicenter study. Am J Gastroenterol 2005;100:2503-9.  Back to cited text no. 10
    
11.
Lindgren S, Wikman O, Befrits R, Blom H, Eriksson A, Grännö C, et al. Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: A randomized, controlled, evaluator-blind, multicentre study. Scand J Gastroenterol 2009;44:838-45.  Back to cited text no. 11
    
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Okam MM, Koch TA, Tran MH. Iron deficiency anemia treatment response to oral iron therapy: A pooled analysis of five randomized controlled trials. Haematologica 2016;101:e6-7.  Back to cited text no. 12
    
13.
Zager RA, Johnson AC, Hanson SY, Wasse H. Parenteral iron formulations: A comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis 2002;40:90-103.  Back to cited text no. 13
    
14.
Kalra PA, Bhandari S. Safety of intravenous iron use in chronic kidney disease. Curr Opin Nephrol Hypertens 2016;25:529-35.  Back to cited text no. 14
    
15.
Jahn MR, Andreasen HB, Fütterer S, Nawroth T, Schünemann V, Kolb U, et al. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm 2011;78:480-91.  Back to cited text no. 15
    
16.
Holm C, Thomsen LL, Norgaard A, Langhoff-Roos J. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: Study protocol for a randomised controlled trial. Trials 2015;16:5.  Back to cited text no. 16
    
17.
Holm C, Thomsen LL, Norgaard A, Langhoff-Roos J. Iron content in breast milk from mothers treated with a high single dose infusion of iron isomaltoside 1000(Monofer). Int J Gynecol Obstet 2015;131 Suppl 5:E119. Erratum: Int J Gynecol Obstet. 2015;131 Suppl 5:E118.  Back to cited text no. 17
    
18.
Wikström B, Bhandari S, Barany P, Kalra PA, Ladefoged S, Wilske J, et al. Iron isomaltoside 1000: A new intravenous iron for treating iron deficiency in chronic kidney disease. J Nephrol 2011;24:589-96.  Back to cited text no. 18
    
19.
Kalra PA, Bhandari S, Saxena S, Agarwal D, Wirtz G, Kletzmayr J, et al. A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney disease patients with anaemia. Nephrol Dial Transplant 2016;31:646-55.  Back to cited text no. 19
    
20.
Reinisch W, Staun M, Tandon RK, Altorjay I, Thillainayagam AV, Gratzer C, et al. A randomized, open-label, non-inferiority study of intravenous iron isomaltoside 1,000 (Monofer) compared with oral iron for treatment of anemia in IBD (PROCEED). Am J Gastroenterol 2013;108:1877-88.  Back to cited text no. 20
    
21.
Dermana R, Thomsenb LL, Auerbachc M. Iron isomaltoside (Monofer®) versus iron sucrose (Venofer®)-a comparative phase 3 trial in patients with iron deficiency anaemia. Abstr Eur J Obstet Gynecol Reprod Biol 2016;206:e128-93.  Back to cited text no. 21
    


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