The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose

Funk, Felix; Ryle, Peter R.; Canclini, Camillo; Neiser, Susann; Geisser, Peter

doi:10.1055/s-0031-1296299

Cited by 54 publications

(70 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Animal studies have shown it to be rapidly eliminated from the plasma, giving minimal risk of large amounts of ionic iron in the plasma. In iron deficient rats, most of the iron has been incorporated into new erythrocytes by 28 d (Funk et al, 2010).…”

Section: Fast Acting Intravenous Iron Preparationsmentioning

confidence: 99%

UK guidelines on the management of iron deficiency in pregnancy

et al. 2012

View full text Add to dashboard Cite

SummaryIron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach. Keywords: iron, iron depletion, iron deficiency, anaemia, pregnancy.The guideline group was selected by the British Society for Haematology, Obstetric Haematology Group (BSH OHG) and British Committee for Standards in Haematology (BCSH), to be representative of UK-based medical experts. MEDLINE and EMBASE were searched systematically for publications from 1966 until 2010 using the terms iron, anaemia, transfusion and pregnancy. Opinions were also sought from experienced obstetricians and practice development midwives. The writing group produced the draft guideline, which was subsequently considered by the members of the BSH Obstetric Haematology Group and revised by consensus by members of the General Haematology Task Force of the BCSH. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH and the BSH Committee and comments incorporated where appropriate. Criteria used to quote levels of recommendation and grades of evidence are as outlined in the Procedure for Guidelines Commissioned by the BCSH. Summary of key recommendations• Anaemia is defined by Hb <110 g/l in the first trimester, <105 g/l in the second and third trimesters and <100 g/l in the postpartum period.• Full blood count (FBC) should be assessed at booking and at 28 weeks.• All women should be given dietary information to maximize iron intake and absorption.• Routine iron supplementation for all women in pregnancy is not recommended in the UK.• Unselected screening with routine use of serum ferritin is generally not recommended although individual centres with a particularly high prevalence of 'at risk' women may find this useful.• For anaemic women, a trial of oral iron should be considered as the first line diagnostic test, whereby an increment demonstrated at 2 weeks is a positive result.• Women with known haemoglobinopathy should have serum ferritin checked and offered oral supplements if their ferritin level is <30 lg/l. • Women with unknown haemoglobinopathy status with a normocyti...

show abstract

Section: Fast Acting Intravenous Iron Preparationsmentioning

confidence: 99%

UK guidelines on the management of iron deficiency in pregnancy

et al. 2012

View full text Add to dashboard Cite

show abstract

“…2, the pharmacokinetic of IV iron is substantially different from that of oral iron. Once injected in the bloodstream (hence circumventing problems in intestinal absorption), IV iron is mainly taken up by macrophages, which subsequently release the element through ferroportin [101]. However, less stable complexes can release variable amount of ferric iron directly in the circulation before macrophage uptake.…”

Section: The Chemistry Of Different IV Iron Preparations and Its Relamentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

View full text Add to dashboard Cite

Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

show abstract

“…Together, the toxicity studies undertaken in rats and dogs show that iron accumulation resulting from administration of sucroferric oxyhydroxide is low and below toxic levels, even with long-term use at high doses [42]. Moreover, at clinically-relevant doses of  40 mg Fe/kg/day, sucroferric oxyhydroxide was not associated with significant increases in liver, spleen or kidney iron values compared with controls after 2 years of administration in rats or after 39 weeks of administration in dogs.…”

Section: Preclinical Data Reviewmentioning

confidence: 99%

“…In humans, iron is stored in ferritin, which consists of an iron (III)-oxyhydroxide core stabilised by a protein shell, and it is transported in transferrin, a glycoprotein consisting of a single polypeptide chain with two iron-binding sites [41, 42]. Iron is mainly stored in the liver and spleen in hepatocytes and macrophages, but the maintenance of iron levels is regulated by absorption in the small intestine [38, 43].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide

Cozzolino

Funk²,

Rakov³

et al. 2015

CDM

Self Cite

View full text Add to dashboard Cite

Sucroferric oxyhydroxide (VELPHORO®) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phosphate binders do not provide the optimal combination of good efficacy, adequate tolerability and low pill burden, sucroferric oxyhydroxide constitutes a promising alternative. Among the attributes of an ideal phosphate binder is minimal absorption and, hence, low risk of systemic toxicity. Accordingly, the iron-releasing properties and absorption, distribution, metabolism and excretion (ADME) profile of sucroferric oxyhydroxide, as well as the possibility of iron accumulation and toxicity, were investigated in a series of preclinical studies. The effect of sucroferric oxyhydroxide on the progression of vascular calcification was also investigated. Sucroferric oxyhydroxide exhibited a high phosphate-binding capacity and low iron-releasing properties across the physiological pH range found in the gastrointestinal tract. In the ADME studies, uptake of 59Fe-radiolabelled sucroferric oxyhydroxide was low in rats and dogs (<1% from a 50 mg Fe/kg bodyweight dose), with the majority of absorbed iron located in red blood cells. Long-term (up to 2 years) administration of sucroferric oxyhydroxide in rats and dogs was associated with modest increases in tissue iron levels and no iron toxicity. Moreoever, in uraemic rats, sucroferric oxyhydroxide was associated with reduced progression of vascular calcification compared with calcium carbonate. In conclusion, sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity.

show abstract

The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose

Cited by 54 publications

References 5 publications

UK guidelines on the management of iron deficiency in pregnancy

UK guidelines on the management of iron deficiency in pregnancy

Modern iron replacement therapy: clinical and pathophysiological insights

Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide

Contact Info

Product

Resources

About