Physico-chemical properties of the new generation IV iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose

Neiser, Susann; Rentsch, Daniel; Dippon, Urs; Kappler, Andreas; Weidler, Peter G.; Göttlicher, Jörg; Steininger, Ralph; Wilhelm, Maria; Braitsch, Michaela; Funk, Felix; Philipp, Erik; Burckhardt, Susanna

doi:10.1007/s10534-015-9845-9

Cited by 70 publications

(91 citation statements)

References 53 publications

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“…This is consistent with studies on labile-free iron release of different preparations, showing the lowest levels with FCM [113]. Because of its high stability, FCM can be quickly administered at high dose, up to 1000 mg of elemental iron in 15 min [114].…”

Section: The Newer IV Iron Preparationssupporting

confidence: 90%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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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.

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Section: The Newer IV Iron Preparationssupporting

confidence: 90%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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“…They can be classified as non-dextran-derived and dextran-derived complexes depending on their carbohydrate shell. In non-dextran-derived complexes, such as ferric carboxymaltose, a higher molecular weight leads to a more stable complex and lower labile iron release [29, 34]. In dextran-derived complexes, however, there is no correlation between complex stability and molecular weight [29, 34, 35].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Reported Rates of Severe Hypersensitivity Reactions Associated with Ferric Carboxymaltose and Iron (III) Isomaltoside 1000 in Europe Based on Data from EudraVigilance and VigiBase™ between 2014 and 2017

Ehlken¹,

Nathell²,

Gohlke³

et al. 2018

Drug Saf

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IntroductionHypersensitivity reactions (HSRs) are among the known adverse events of intravenous (i.v.) iron products. Of these, particularly severe HSRs such as anaphylaxis are of great clinical concern due to their life-threatening potential.MethodsThis was a retrospective pharmacoepidemiological study with a case-population design evaluating the number of reported severe HSRs following administration of the two i.v. iron products—ferric carboxymaltose and iron (III) isomaltoside 1000—in relation to exposure in European countries from January 2014 to December 2017. Exposure to both products was estimated using IQVIA MIDAS sales data in European countries. Information on spontaneously reported severe HSRs was obtained from and analysed separately for the two established safety surveillance databases EudraVigilance and VigiBase™ using the MedDRA® Preferred Terms anaphylactic reaction, anaphylactic shock, anaphylactoid reaction and anaphylactoid shock associated with administration of either product.ResultsBetween 2014 and 2017, the reporting rate of severe HSRs per 100,000 defined daily doses (100 mg dose equivalents of iron) varied from 0.3 to 0.5 for ferric carboxymaltose and from 2.4 to 5.0 for iron (III) isomaltoside 1000. The reporting rate ratio for iron (III) isomaltoside 1000 versus ferric carboxymaltose was between 5.6 (95% CI 3.5–9.0) and 16.2 (95% CI 9.4–27.8).ConclusionsFindings suggest that iron (III) isomaltoside 1000 is associated with a higher reporting rate of severe HSRs related to estimated exposure than ferric carboxymaltose in European countries. Future research investigating the occurrence of severe HSRs associated with i.v. ferric carboxymaltose and iron (III) isomaltoside 1000 is needed to broaden the evidence for benefit-risk assessment.

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“…Iron in a free state might be leading to anaphylactic-like symptoms or might be the reason for the skin erythema in one of the patients (34). However, a recently published study shows that if applied according to recommendations, only a minimum of free iron emerges from ferumoxytol during intravenous injection (35) and that this amount of free iron should not have any clinical relevance (36). A previous study showed that high-rate, high-volume administration of iron-carbohydrate compounds can lead to hypotension, nausea, back and chest pain through complement activation by labile iron (37).…”

Section: Discussionmentioning

confidence: 99%

Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults

Muehe

Feng

Eyben

et al. 2016

Investigative Radiology

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Objective To assess the safety profile of ferumoxytol as an intravenous magnetic resonance (MR) imaging contrast agent in children. Materials and Methods We prospectively evaluated the safety of ferumoxytol administrations as an “off-label” contrast agent for MR imaging in non-randomized phase IV clinical trials at two centers. From September 2009 to February 2015 49 pediatric patients (21 female and 28 male, 5-18 years old) and 19 young adults (8 female and 11 male, 18-25 years old) were reported under an investigator-initiated investigational new drug (IND) investigation with institutional review board (IRB) approval, in health insurance portability and accountability act (HIPAA) compliance, and after written informed consent of the child's legal representative or the competent adult patient was obtained. Patients received either a single dose (5 mg Fe/kg) or up to 4 doses of ferumoxytol (0.7-4 mg Fe/kg) intravenously, which were approximately equivalent to 1/3 of the dose for anemia treatment. We monitored vital signs and adverse events directly for up to one hour post injection. In addition, we examined weekly vitals, hematologic, renal and liver serum panels for one month after injection in over 20 pediatric patients. At fixed time points before and after ferumoxytol injection data were evaluated for significant differences by a repeated measures linear mixed model. Results Four mild adverse events, thought to be related to ferumoxytol, were observed within one hour of 85 ferumoxytol injections: Two episodes of mild hypotension and one case of nausea in 65 injections in pediatric patients without related clinical symptoms. One young adult patient developed warmness and erythema at the injection site. All adverse events were self-resolving. No spontaneous serious adverse events were reported. At a dose of 5 mg Fe/kg or lower, intravenous ferumoxytol injection had no clinical relevance or statistically significant effect (p>0.05) on vital signs, hematological parameters, kidney function or liver enzymes within one month of the injection. Conclusion Ferumoxytol was overall well tolerated among 49 pediatric and 19 young adult patients suffering from various tumors or kidney transplants without major adverse events or signs of hematologic and kidney impairment or liver toxicity. Larger studies are needed to determine the incidence of anaphylactic reactions.

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Physico-chemical properties of the new generation IV iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose

Cited by 70 publications

References 53 publications

Modern iron replacement therapy: clinical and pathophysiological insights

Modern iron replacement therapy: clinical and pathophysiological insights

Evaluation of the Reported Rates of Severe Hypersensitivity Reactions Associated with Ferric Carboxymaltose and Iron (III) Isomaltoside 1000 in Europe Based on Data from EudraVigilance and VigiBase™ between 2014 and 2017

Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults

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