Evaluation of Hypersensitivity Reactions to Ferric Carboxymaltose in Iron - Deficiency Anemia Patients: A Multicenter Randomized Trial

Iron deficiency anaemia is a widespread nutritional condition affecting physical and psychological well - being globally. While oral iron therapy is the standard treatment, its effectiveness can vary due to multiple factors. This has led to the emergence of intravenous iron therapies, such as Ferric Carboxymaltose (FCM), as an alternative for patients with inadequate responses to oral iron. Concerns regarding hypersensitivity reactions have arisen with intravenous iron, necessitating a detailed investigation. In this study, we evaluate the safety and efficacy of FCM compared to oral iron therapy in adult patients with iron deficiency anaemia and heart failure. Our research encompasses animal and human trials, with guinea pig tests revealing a 0% hypersensitivity rate for FCM. Additionally, a clinical trial involving 100 human subjects from various regions demonstrates no instances of hypersensitivity reactions. These findings suggest that FCM is a safe alternative for patient...

Iron deficiency anaemia is a well - known form of nutritional anaemia globally. Iron deficiency anaemia can affect both physical as well as psychological functioning of human beings. Although, oral iron is considered as the first - line therapeutic regimen of iron deficiency anaemia, the absorption of oral iron might vary by several factors. This has led to the development of intravenous iron therapy, especially Ferric Carboxymaltose (FCM), which is a novel non - dextran form of intravenous iron approved for patients with iron deficiency anaemia and have insufficient response to oral iron therapy.1 To demonstrate the efficacy and safety profile of FCM in comparison to oral iron to the adult patients who have iron deficiency anaemia and heart failure, previousmulticentre, open label, randomized, single - dose, two - treatment, parallel arm bioequivalence study has been performed. Several trials have described the sustained improvement of patient outcomes in cases with heart failure as well2 . However, the question arises regarding the safety profile of the drug Ferric Carboxymaltose, whether this is non - hypersensitive after its administration to human subjects or not. Several iron infusion complexes are available to treat iron deficiency anaemia. Iron dextran is associated with elevated risks of potentially threatened anaphylactic reactions; whereas FCM if administered in a single dosage is comparatively safe.3 - 4Hypersensitivity is recognized as an immunologically mediated allergic reaction occurring against substances, chemicals, cosmetics, or pharmaceutical products. In order to assess or evaluate toxic characteristics of a drug, it is important to determine its potential of triggering hypersensitivity reactions before - hand. Intravenous administration of iron may cause hypersensitivity reaction. Clinical research has shown that intravenous iron preparation though well - tolerated in patients still caused death in some cases. There are reports on anaphylactic shock and death related to FCM infusion as well.3It has been reported that the risk of hypersensitivity reactions associated with FCM is comparatively lower than iron dextran preparation due to non - dextran carbohydrate moiety of FCM. The reports suggest that annual exposure of iron dextran has been decreased globally in between the years of 2008 and 2017, whereas, the annual exposure of FCM has been increased over the same period and the cumulative global exposures of these two drugs are represented in the figure below. From 2008 to 2017 the global exposure of iron dextran has been decreased from 14.4 million to 9.7 million, while the global exposure of FCM has been increased from 0.6 million to 24.2 million (Fig.2). Also, the global reported rate of hypersensitivity reactions (anaphylactic shock) is much higher for iron dextran compared to FCM (Fig.3).5 The present study focuses on determination of efficacy and safety profile of FCM sponsored by Eskag Pharma Pvt. Ltd. To determine hypersensitivity potential of the drug Ferric Carboxymaltose sponsored by Eskag Pharma Pvt Ltd, Following this event, the present clinical trial is conducted by incorporating human subjects from four different regions in Kolkata and Howrah to identify whether Ferric Carboxymaltose drug is also non - hypersensitive to human subjects. A total of 100 population are included in the study from the regions of Behala, Basirhat, Howrah, and ID & BG. All of them are infused with diluted drug concentration to observe whether they develop any kind of analyphlactic shock, respiratory troubles, restlessness, or not. The pre - trial and post - trial physiological conditions of the human population are recorded.animal tests have been done with guinea pigs. The evaluation of hypersensitivity reactions of Ferric Carboxymaltose injection, sponsored by Eskag Pharma Pvt. Ltd., was conducted at Bioscience Research Foundation in male and female guinea pigs using Magnusson and Kligman method following the rules of Drugs and Cosmetics - Schedule Y Guideline, 2019. None of the animals of the test group showed any sort of allergic reactions after application of Ferric Carboxymaltose injection. It proved the hypersensitivity activity rate of Ferric Carboxymaltose drug to be 0% and the drug has been classified as non - allergic under experimental conditions. 2. Study Design 2.1. Overview A multicenter, randomized trialis designed to assess hypersensitivity profile of intravenous FCM drug for the treatment of iron deficiency anaemia. In accordance with the instruction of the sponsor Eskag Pharma on the basis of their clinical experience, it has been recommended that the rate of iron infusion should be 50% at initiation, and the rate should not be increased until it is ascertained to be well - tolerated by the patient in 15 - 20 minutes. For the ease of recognition as well as appropriate management of hypersensitivity reactions to FCM formulation (...