Intravenous iron: do we adequately understand the short‐ and long‐term risks in clinical practice?

Rund, Deborah

doi:10.1111/bjh.17202

Cited by 17 publications

(15 citation statements)

References 116 publications

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“…Another example of successful medical use of MNPs is the drug Ferumoxytol (commercial names Ferahem ® in the United States, Rienso ® in the EU) [ 187 – 189 ]. It was originally approved by the FDA in 2009 for the treatment of anemia in patients with renal failure for whom conventional drugs were either toxic or ineffective [ 190 ].…”

Section: Progress In Medical Application Of Magnetic Nanoparticlesmentioning

confidence: 99%

Magnetic Nanoparticles in Medicine: Progress, Problems, and Advances

Koksharov

Губин

Taranov

et al. 2022

J. Commun. Technol. Electron.

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The review presents an analysis of the current state of research related to the design, development, and practical application of methods for biomedical radioelectronics and nanomedicine, including the use of magnetic nanoparticles. The important role of rational scientific physical approaches and experimental methods in the design of efficient and safe magnetic nanoparticle-based agents for therapy, controlled targeted drug delivery, and diagnostics, including spatial imaging, is emphasized. Examples of successful practical application of magnetic nanoparticles in medicine based on these methods are given, and an analysis of the main problems and prospects of this area of science is conducted.

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Section: Progress In Medical Application Of Magnetic Nanoparticlesmentioning

confidence: 99%

Magnetic Nanoparticles in Medicine: Progress, Problems, and Advances

Koksharov

Губин

Taranov

et al. 2022

J. Commun. Technol. Electron.

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“…However, adverse events are usually a secondary outcome parameter and the trials were not powered on infrequent adverse events. Mild to moderate hypersensitivity reactions or other mild adverse events (excluding hypophosphatemia) occur more frequently but the incidence rates vary widely, depending on terminology and the type of intravenous iron formulation [ 135 ]. A universal approach with a standardized method grading hypersensitivity reactions in adequately powered prospective studies could provide a more definite answer as to whether the different intravenous iron formulations truly differ in the incidence of adverse events.…”

Section: Hypersensitivity Reactionsmentioning

confidence: 99%

High-Dose Intravenous Iron with Either Ferric Carboxymaltose or Ferric Derisomaltose: A Benefit-Risk Assessment

Boots

Quax

2022

Drug Saf

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The intravenous iron formulations ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) offer the possibility of administering a large amount of iron in one infusion. This results in faster correction of anemia and the formulations being better tolerated than oral iron formulations. This triad of logistic advantages, improved patient convenience, and fast correction of anemia explains the fact that intravenous iron formulations nowadays are frequently prescribed worldwide in the treatment of iron deficiency anemia. However, these formulations may result in hypophosphatemia by inducing a strong increase in active fibroblast growth factor-23 (FGF-23), a hormone that stimulates renal phosphate excretion. This effect is much more pronounced with FCM than with FDI, and therefore the risk of developing hypophosphatemia is remarkably higher with FCM than with FDI. Repeated use of FCM may result in severe osteomalacia, which is characterized by bone pain, Looser zones (pseudofractures), and low-trauma fractures. Intravenous iron preparations are also associated with other adverse effects, of which hypersensitivity reactions are the most important and are usually the result of a non-allergic complement activation on nanoparticles of free labile iron—Complement Activation-Related Pseudo-Allergy (CARPA). The risk on these hypersensitivity reactions can be reduced by choosing a slow infusion rate. Severe hypersensitivity reactions were reported in < 1% of prospective trials and the incidence seems comparable between the two formulations. A practical guideline has been developed based on baseline serum phosphate concentrations and predisposing risk factors, derived from published cases and risk factor analyses from trials, in order to establish the safe use of these formulations.

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“…In each case, specific conditions are applied and appropriate protocols need to be designed. For example, intravenous trimaltol iron complex formulations may have to be designed to benefit IDA cancer and other categories of patients [ 28 , 214 , 215 , 216 ]. Mixed chelator iron complexes of maltol and ascorbate may also be designed for increasing the efficacy of gastrointestinal iron uptake for the treatment of IDA.…”

Section: Potential Applications Of Maltol and Maltol Metal Complexes In Medicinementioning

confidence: 99%

New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications

Kontoghiorghes¹,

Kolnagou²,

Demetriou³

et al. 2021

IJMS

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The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980–1981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978–1981), which were intended for clinical use, including the treatment of iron deficiency anaemia (IDA). Iron deficiency anaemia is a global health problem affecting about one-third of the world’s population. Many (and different) ferrous and ferric iron complex formulations are widely available and sold worldwide over the counter for the treatment of IDA. Almost all such complexes suffer from instability in the acidic environment of the stomach and competition from other dietary molecules or drugs. Natural and synthetic lipophilic KHP chelators, including maltol, have been shown in in vitro and in vivo studies to form stable iron complexes, to transfer iron across cell membranes, and to increase iron absorption in animals. Trimaltol iron, sold as Feraccru or Accrufer, was recently approved for clinical use in IDA patients in many countries, including the USA and in EU countries, and was shown to be effective and safe, with a better therapeutic index in comparison to other iron formulations. Similar properties of increased iron absorption were also shown by lipophilic iron complexes of 8-hydroxyquinoline, tropolone, 2-hydroxy-4-methoxypyridine-1-oxide, and related analogues. The interactions of the KHP iron complexes with natural chelators, drugs, metal ions, proteins, and other molecules appear to affect the pharmacological and metabolic effects of both iron and the KHP chelators. A new era in the treatment of IDA and other possible clinical applications, such as theranostic and anticancer formulations and metal radiotracers in diagnostic medicine, are envisaged from the introduction of maltol, KHP, and similar lipophilic chelators.

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Intravenous iron: do we adequately understand the short‐ and long‐term risks in clinical practice?

Cited by 17 publications

References 116 publications

Magnetic Nanoparticles in Medicine: Progress, Problems, and Advances

Magnetic Nanoparticles in Medicine: Progress, Problems, and Advances

High-Dose Intravenous Iron with Either Ferric Carboxymaltose or Ferric Derisomaltose: A Benefit-Risk Assessment

New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications

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