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Ferric Carboxymaltose

A Review of its Use in Iron-Deficiency Anaemia

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Summary

Abstract

Ferric carboxymaltose (Ferinject®), a novel iron complex that consists of a ferric hydroxide core stabilized by a carbohydrate shell, allows for controlled delivery of iron to target tissues. Administered intravenously, it is effective in the treatment of iron-deficiency anaemia, delivering a replenishment dose of up to 1000 mg of iron during a minimum administration time of ≤15 minutes. Results of several randomized trials have shown that intravenously administered ferric carboxymaltose rapidly improves haemoglobin levels and replenishes depleted iron stores in various populations of patients with iron-deficiency anaemia, including those with inflammatory bowel disease, heavy uterine bleeding, postpartum irondeficiency anaemia or chronic kidney disease. It was well tolerated in clinical trials. Ferric carboxymaltose is, therefore, an effective option in the treatment of iron-deficiency anaemia in patients for whom oral iron preparations are ineffective or cannot be administered.

Pharmacological Properties

Ferric carboxymaltose is a macromolecular ferric hydroxide carbohydrate complex, which allows for controlled delivery of iron within the cells of the reticuloendothelial system and subsequent delivery to the iron-binding proteins ferritin and transferrin, with minimal risk of release of large amounts of ionic iron in the serum. Intravenous administration of ferric carboxymaltose results in transient elevations in serum iron, serum ferritin and transferrin saturation, and, ultimately, in the correction of haemoglobin levels and replenishment of depleted iron stores.

The total iron concentration in the serum increased rapidly in a dose-dependent manner after intravenous administration of ferric carboxymaltose. Ferric carboxymaltose is rapidly cleared from the circulation and is distributed primarily to the bone marrow (≈80%) and also to the liver and spleen. Repeated weekly administration of ferric carboxymaltose does not result in accumulation of transferrin iron in patients with iron-deficiency anaemia.

Therapeutic Efficacy

Intravenously administered ferric carboxymaltose was effective in the treatment of iron-deficiency anaemia in several 6- to 12-week, randomized, open-label, controlled, multicentre trials in various patient populations, including those with inflammatory bowel disease, heavy uterine bleeding or postpartum irondeficiency anaemia, and those with chronic kidney disease not undergoing or undergoing haemodialysis. In most trials, patients received either ferric carboxymaltose equivalent to an iron dose of ≤1000mg (or 15mg/kg in those weighing <66kg) administered over ≤15 minutes (subsequent doses administered at 1-week intervals) or oral ferrous sulfate at a dose equivalent to 65 mg iron three times daily or 100mg iron twice daily. In one trial, patients with chronic kidney disease undergoing haemodialysis received 200 mg of iron intravenously either as ferric carboxymaltose or iron sucrose administered into the haemodialysis line two to three times weekly. In all trials, ferric carboxymaltose was administered until each patient had received his or her calculated total iron replacement dose.

Haemoglobin-related outcomes improved in patients with iron-deficiency anaemia receiving ferric carboxymaltose. Treatment with ferric carboxymaltose was associated with rapid and sustained increases from baseline in haemoglobin levels. Ferric carboxymaltose was considered to be as least as effective as ferrous sulfate with regard to changes from baseline in haemoglobin levels or the proportion of patients achieving a haematopoietic response at various timepoints. In general, improvements in haemoglobin levels were more rapid with ferric carboxymaltose than with ferrous sulfate. In patients with chronic kidney disease undergoing haemodialysis, ferric carboxymaltose was at least as effective as iron sucrose.

Ferric carboxymaltose also replenished depleted iron stores and improved health-related quality-of-life (HR-QOL) in patients with iron-deficiency anaemia. Recipients of ferric carboxymaltose demonstrated improvements from baseline in serum ferritin levels and transferrin saturation, as well as improvements from baseline in HR-QOL assessment scores. Ferric carboxymaltose was at least as effective as ferrous sulfate with regard to endpoints related to serum ferritin levels, transferrin saturation and HR-QOL.

Tolerability

Ferric carboxymaltose was well tolerated in clinical trials in patients with irondeficiency anaemia, with most drug-related adverse events considered to be mild to moderate in severity. Commonly reported drug-related adverse events include headache, dizziness, nausea, abdominal pain, constipation, diarrhoea, rash and injection-site reactions.

The incidence of drug-related adverse events in patients receiving intravenous ferric carboxymaltose was generally similar to that in patients receiving oral ferrous sulfate. In general, rash and local injection-site reactions were more common with ferric carboxymaltose, whereas gastrointestinal adverse events were more frequent with ferrous sulfate. In patients with chronic kidney disease undergoing haemodialysis, a lower proportion of ferric carboxymaltose than iron sucrose recipients experienced at least one drug-related adverse event.

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Authors and Affiliations

  1. Wolters Kluwer Health ¦ Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, Auckland, 0754, New Zealand

    Katherine A. Lyseng-Williamson & Gillian M. Keating

  2. Wolters Kluwer Health, Philadelphia, Pennsylvania, USA

    Katherine A. Lyseng-Williamson & Gillian M. Keating

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  1. Katherine A. Lyseng-Williamson
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  2. Gillian M. Keating
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Correspondence to Katherine A. Lyseng-Williamson.

Additional information

Various sections of the manuscript reviewed by: I. Cavill, Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom; C. Gasche, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; F. Gomollón, Gastroenterology Service, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; I.E. Koutroubakis, Department of Gastroenterology, University Hospital Heraklion, Heraklion, Greece; T.J. Littlewood, Department of Haematology, John Radcliffe Hospital, Oxford, United Kingdom; F. Locatelli, Department of Nephrology, Dialysis and Renal Transplantation, A. Manzoni Hospital, Lecco, Italy; W.Y. Qunibi, Department of Medicine, University of Texas Health Sciences Center, San Antonio, Texas, USA; M.H. Seid, Lyndhurst Gynecologic Associates, Winston-Salem, North Carolina, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘ferric carboxymaltose’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Wolters Kluwer Health ∣ Adis). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘ferric carboxymaltose’. Searches were last updated 16 April 2009.

Selection: Studies in patients with iron-deficiency anaemia who received ferric carboxymaltose. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Ferric carboxymaltose, iron-deficiency anaemia, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Lyseng-Williamson, K.A., Keating, G.M. Ferric Carboxymaltose. Drugs 69, 739–756 (2009). https://doi.org/10.2165/00003495-200969060-00007

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