Modern iron replacement therapy: clinical and pathophysiological insights

Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

doi:10.1007/s12185-017-2373-3

Cited by 142 publications

(142 citation statements)

References 134 publications

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“…There is great interest in the development of compounds better tolerated than iron salts; numerous compounds have been proposed (eg, sucrosomial iron, heme iron polypeptide, iron containing nanoparticles), but studies are limited. 79 Sucrosomial iron has been tested in patients with CKD, 80 but the mechanism of absorption and the real benefits are uncertain. In the same condition, the phosphate binder iron ferric citrate simultaneously corrects both hyperphosphatemia and iron deficiency; its double effect is being tested in a clinical trial in CKD.…”

Section: Oral Iron Supplementationmentioning

confidence: 99%

Iron deficiency

Camaschella¹

2019

Blood

407

415

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Iron deficiency anemia affects >1.2 billions individuals worldwide, and iron deficiency in the absence of anemia is even more frequent. Total-body (absolute) iron deficiency is caused by physiologically increased iron requirements in children, adolescents, young and pregnant women, by reduced iron intake, or by pathological defective absorption or chronic blood loss. Adaptation to iron deficiency at the tissue level is controlled by iron regulatory proteins to increase iron uptake and retention; at the systemic level, suppression of the iron hormone hepcidin increases iron release to plasma by absorptive enterocytes and recycling macrophages. The diagnosis of absolute iron deficiency is easy unless the condition is masked by inflammatory conditions. All cases of iron deficiency should be assessed for treatment and underlying cause. Special attention is needed in areas endemic for malaria and other infections to avoid worsening of infection by iron treatment. Ongoing efforts aim at optimizing iron salts–based therapy by protocols of administration based on the physiology of hepcidin control and reducing the common adverse effects of oral iron. IV iron, especially last-generation compounds administered at high doses in single infusions, is becoming an effective alternative in an increasing number of conditions because of a more rapid and persistent hematological response and acceptable safety profile. Risks/benefits of the different treatments should be weighed in a personalized therapeutic approach to iron deficiency.

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Section: Oral Iron Supplementationmentioning

confidence: 99%

Iron deficiency

Camaschella¹

2019

Blood

407

415

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“…Although iron is thought to be safe enough to be available over the counter, its use is associated with many problems [7]. Up to 30–70% of patients will have complaints of gastrointestinal upset.…”

Section: Risks Of Oral Ironmentioning

confidence: 99%

“…There are multiple products to choose from when giving intravenous iron (Tables 1, 2). All iron products are composed of a polynuclear iron core with a surrounding shell of carbohydrates for stabilization [7]. It is the composition of the carbohydrate shell that differentiates the iron products from each other.…”

Section: Risks Of Intravenous Ironmentioning

confidence: 99%

Safety of Oral and Intravenous Iron

DeLoughery

2019

Acta Haematol

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As the adverse effects of iron deficiency are better recognized, the use of oral and intravenous iron has increased dramatically. Oral iron is often poorly tolerated, with up to 70% or more of patients noting gastrointestinal issues; this may affect adherence to therapy. In addition, many patients will not respond to oral iron due to their underlying illness. Intravenous iron is being used more frequently to replete iron stores. True anaphylaxis is very rare, but complement-mediated infusion reactions may be seen in up to 1 in every 200 patients. Previous concerns about intravenous iron increasing the risk of infection or cardiovascular disease are unfounded.

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“…iron is generally considered safe, iron infusions can cause hypersensitivity reactions (HSRs) [11, 12]. As these reactions may range from mild to fatal, HSRs are of great clinical concern, especially anaphylaxis [13, 14]. Anaphylaxis is the umbrella term for an acute reaction defined as follows: a severe, life-threatening generalized or systemic hypersensitivity reaction.…”

Section: Introductionmentioning

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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Modern iron replacement therapy: clinical and pathophysiological insights

Cited by 142 publications

References 134 publications

Iron deficiency

Iron deficiency

Safety of Oral and Intravenous Iron

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

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