On the relative safety of parenteral iron formulations

Chertow, Glenn M.; Mason, Phillip D.; Vaage-Nilsen, Odd; Ahlmén, J

doi:10.1093/ndt/gfh185

Cited by 137 publications

(115 citation statements)

References 16 publications

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“…98 A number of studies document that anaphylaxis, the serious adverse event associated with iron dextran, is largely due to the two high molecular weight products, Imferon, which is no longer available, and Dexferrum, which is not recommended. 40,42,48,49,53,[99][100][101][102][103][104][105][106] Iron sucrose has the least reported adverse events and high molecular weight iron dextran has the highest number of reported adverse events. Low molecular weight iron dextran and ferric gluconate fall in between these two for the number of adverse drug events.…”

Section: Resultsmentioning

confidence: 99%

“…Low molecular weight iron dextran and ferric gluconate fall in between these two for the number of adverse drug events. 40,46,48,56,60,98 Anaphylactic reactions have predominantly been reported with the use of iron dextran. 50,51 Comparisons of the iron sucrose or iron gluconate to low molecular weight iron dextran show no difference in toxicity or efficacy but considerable savings and ease of administration with low molecular weight iron dextran.…”

Section: Resultsmentioning

confidence: 99%

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Safety Issues With Intravenous Iron Products in the Management of Anemia in Chronic Kidney Disease

Hayat¹

2008

Clinical Medicine & Research

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Safety Issues With Intravenous Iron Products in the Management of Anemia in Chronic Kidney Disease

Hayat¹

2008

Clinical Medicine & Research

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“…At least two studies [2,3] have implicated the higher molecular weight iron dextran, Dexferrum, with substantially higher incidence of anaphylactic-type reactions than the lower molecular weight iron dextran, INFeD, and an editorial [4] requested that FDA remove Dexferrum from the market. However, these studies used as evidence voluntarily submitted reports of adverse drug events entered in the FDA's database.…”

Section: Discussionmentioning

confidence: 99%

“…At least two studies [2,3] have implicated the higher molecular weight iron dextran, Dexferrum, with substantially higher frequencies of life-threatening adverse drug events including anaphylactic-type reactions than the lower molecular weight iron dextran, INFeD. An editorial published in 2008 [4] stated, ''We urgently recommend avoiding use of HMW iron dextran in all clinical practice settings.…”

Section: Introductionmentioning

confidence: 99%

Use of parenteral iron products and serious anaphylactic‐type reactions

Wysowski¹,

Swartz²,

Borders-Hemphill³

et al. 2010

American J Hematol

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Controversy exists about the safety of the parenteral iron dextran products, Dexferrum and INFeD, which have been associated with rare, serious anaphylactic-type reactions. In the United States, their product labels carry boxed warnings of this adverse event; some have called for the withdrawal from marketing of the higher molecular weight Dexferrum. Between 2002 and 2007, sales of Dexferrum, INFeD, and iron gluconate Ferrlecit declined 32.5%, 21%, and 4.8%, respectively, while sales of iron sucrose Venofer increased 160%. Voluntary reports submitted to the Food and Drug Administration show anaphylactic reactions and symptoms for the four parenteral iron products. Because of underreporting, possible differential reporting, absence of iron dextran brand names, and incomplete use (denominator) data, incidence rates and relative risk estimates cannot be calculated. U.S. death certificate data show that for most years from 1979 through 2006, no more than 3 deaths per year were coded to ''adverse events in therapeutic use of iron preparations;'' brand names were not consistently recorded. Emergency department data show small numbers of visits for treatment of allergic reactions with intravenous iron preparations. The data presented herein show that allergic reactions are possible with all four parenteral iron products, and it is difficult to determine which product has the largest risk based on sales data, voluntarily submitted adverse event reports, death certificates, ED visits, and observational studies performed to date. To help differentiate risk among the parenteral iron products, the brand name of the product always should be provided on medical records, death certificates, and adverse drug reaction reports. Am. J.

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“…The accumulated data show that lowmolecular weight iron dextran does not share this higher risk. Studies ranging from dialysis database reviews to a European Medical Agency review have shown no difference in risk with low-molecular weight iron dextran versus other iron products [3][4][5].Recently, this notion of equivalent risk was challenged by a study from the FDA which purported to show a significantly higher rate of "anaphylaxis" with iron dextran compared to other iron products [6]. This study examined 688,183 non-dialysis new users of intravenous iron over 10 years in the outpatient Medicare claims database.…”

mentioning

confidence: 99%

Is low‐molecular weight iron dextran really the most risky iron?—Unconvincing data from an unconvincing study

DeLoughery

Auerbach

2016

American J Hematol

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The use of intravenous iron has expanded over the past few years as accepted indications for its use have increased. It is now recognized that intravenous iron will raise iron stores faster and more reliably in conditions in which oral iron is unlikely to work or poorly tolerated such as chronic kidney disease, inflammatory bowel disease, heavy uterine bleeding, hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu), pregnancy, and those having undergone bariatric surgery. However, the acceptance of this effective therapy by physicians has been hindered by concerns about safety of iron infusions. The use of early formulations, such as ferric hydroxide, was associated with high levels of labile free iron release and an unacceptably high incidence of serious hemodynamically significant infusion reactions. By the early 1950s, products with carbohydrate cores which bound the elemental iron more tightly, such as high-molecular weight iron dextran-ImFeron, (Fisons, Homes Chapel, England) and later DexFerrum, (American Regent, Shirley, New York)-which are no longer available, and iron sucrose, were much better tolerated but still associated with rare anaphylactic reactions. Newer formulations which release labile free iron much more slowly, such as low-molecular weight iron dextran (INFeD, Pfizer, New York, NY), ferumoxytol (Feraheme, AMAG, Waltham, MA), ferric carboxymaltose (InjectoFer, American Regent, Shirley, NY), and iron isomaltoside (Monofer, Europe only, Pharmacosmos, Haelbeck, Denmark) are much better tolerated and provide the added convenience of being able to be administered safely in complete replacement doses over 15-60 min.While there are many factors to consider in the choice of iron products-expense, numbers of infusions, effectiveness-safety is also a key factor. One iron product did stand out in risk-high-molecular weight iron dextran (DexFerrum) which has been shown in several studies to have reaction rates higher than other iron products [1][2][3]. This formulation was removed from market in 2009. The accumulated data show that lowmolecular weight iron dextran does not share this higher risk. Studies ranging from dialysis database reviews to a European Medical Agency review have shown no difference in risk with low-molecular weight iron dextran versus other iron products [3][4][5].Recently, this notion of equivalent risk was challenged by a study from the FDA which purported to show a significantly higher rate of "anaphylaxis" with iron dextran compared to other iron products [6]. This study examined 688,183 non-dialysis new users of intravenous iron over 10 years in the outpatient Medicare claims database. The anaphylaxis rate for iron dextran was compared to iron gluconate, iron sucrose, and ferumoxytol. The key finding was that the rate of anaphylaxis for iron dextran had an odds ratio 2.6 times higher reaction rate than all nondextran irons-68 vs. 23 per 100,000 persons.However, there are several issues with this study that cast doubt on the conclusion that low-molecular weight iron dextra...

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On the relative safety of parenteral iron formulations

Cited by 137 publications

References 16 publications

Safety Issues With Intravenous Iron Products in the Management of Anemia in Chronic Kidney Disease

Safety Issues With Intravenous Iron Products in the Management of Anemia in Chronic Kidney Disease

Use of parenteral iron products and serious anaphylactic‐type reactions

Is low‐molecular weight iron dextran really the most risky iron?—Unconvincing data from an unconvincing study

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