Physicochemical properties of ferumoxytol, a new intravenous iron preparation

Balakrishnan, Vaidyanathapuram S.; Madhumathi, R; Kausz, Annamaria T.; Brenner, Louis; Pereira, Brian J.G.; Frigo, Timothy B.; Lewis, J. M.

doi:10.1111/j.1365-2362.2009.02130.x

Cited by 127 publications

(126 citation statements)

References 27 publications

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“…Over the last several decades, a number of iron oxides with varying carbohydrate shells have been introduced that permit delivery of iron intravenously with very low rates of serious adverse events (SAEs). Two iron preparations, ferric gluconate, and iron sucrose can be administered at low doses over relatively short periods of time, but doses more than 250 mg (ferric gluconate) and 300 mg (iron sucrose) are not recommended [2] due to high rates of infusion reactions, presumably due to free iron release from less tightly bound carbohydrate carriers [3][4][5]. Subsequently, multiple clinic visits are required to provide patients with a 1 g treatment course of IV iron.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

et al. 2013

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For the majority of patients with iron deficiency anemia (IDA), a full course of intravenous (IV) iron is 1 g. Most IV irons require 5–10 administrations of 100–300 mg. We have successfully employed 1 g low molecular weight iron dextran over 1 hr. For further convenience for patients and physicians, we explored the administration of 1.02 g of ferumoxytol over 15 min instead of the approved 2 × 510 mg injections. Sixty patients with IDA, (hemoglobin <11 g/dL, transferrin saturation [TSAT] ≤20%, and ferritin <100 ng/mL) with an inadequate response or intolerance to oral iron, received 1020 mg ferumoxytol over 15 min. Vital signs were measured for 1 hr. Adverse events (AEs) were collected via telephone at 1, 2, and 7 days. Follow‐up visits occurred at 4 and 8 weeks for efficacy assessments. The primary endpoint was safety and tolerability. Secondary efficacy endpoints included mean change in hemoglobin, TSAT, and red cell distribution width. No serious adverse events (SAEs) occurred. Fifty‐eight patients received the planned dose. Twenty‐six out of sixty (43.3%) patients reported AEs of which 13 were mild and transient during infusion. All resolved within minutes. Fourteen patients reported self‐limited arthralgias, myalgias, and/or headache within 24–48 hr. At Baseline, the mean hemoglobin was 9.4 g/dL. The mean increments at Week 4 and 8 were 2.1 and 2.6 g/dL, respectively. Ferumoxytol, administered as 1.02 g infusion over 15 min was well tolerated with no SAEs and demonstrated excellent efficacy. If corroborated in future studies this represents an improved method of treating IDA. Am. J. Heamtol. 88:944–947, 2013. © 2013 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

et al. 2013

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“…[61][62][63] Not surprisingly, IVI formulations have been shown to induce oxidative stress, inflammation and cellular toxicity, pro-oxidant cell signaling, tissue inflammation, cellular iron deposition, and cytotoxicity in cell culture models, animal models, and acutely in human participants [63][64][65][66][67] with more labile compounds inducing more toxicity than those with larger carbohydrate shells. 68,69 IVI has also been associated with immune dysfunction, augmentation of bacterial growth, and increased Gram-positive bacteria growth in vitro.…”

Section: In Vitro Safety Signalsmentioning

confidence: 99%

Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

Charytan

Pai

Chan

et al. 2015

Journal of the American Society of Nephrology

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Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysisdependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population.

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“…The presence of sharp peaks at 10°, 20°, and 40° is consistent with the crystalline mannitol included in the ferumoxytol formulation (ferumoxytol for injection contains 44 mg/mL of mannitol). A mean diameter of 6.4 nm for ferumoxytol cores was calculated using the line broadening of the X-ray diffraction patterns, and it was confirmed by TEM 29,30 (see Figure 1). The hydrodynamic diameter of ferumoxytol, as determined by DLS, was approximately 23 nm, which properly reflects the presence of carbohydrate coating around the iron oxide core.…”

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confidence: 99%

Nanopharmaceuticals (part 2): products in the pipeline

Weissig¹,

Guzmán-Villanueva²

2015

IJN

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In part I of this review we assessed nanoscience-related definitions as applied to pharmaceuticals and we discussed all 43 currently approved drug formulations, which are widely publicized as nanopharmaceuticals or nanomedicines. In continuation, here we review the currently ongoing clinical trials within the broad field of nanomedicine. Confining the definition of nanopharmaceuticals to therapeutic formulations, in which the unique physicochemical properties expressed in the nanosize range, when man-made, play the pivotal therapeutic role, we found an apparently low number of trials, which reflects neither the massive investments made in the field of nanomedicine nor the general hype associated with the term “nano.” Moreover, after an extensive search for information through clinical trials, we found only two clinical trials with materials that show unique nano-based properties, ie, properties that are displayed neither on the atomic nor on the bulk material level.

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Physicochemical properties of ferumoxytol, a new intravenous iron preparation

Abstract: In vitro observations from these experiments suggest that ferumoxytol has a favourable profile in terms of tendency to release free iron, in comparison with currently available intravenous iron preparations.

Cited by 127 publications

References 27 publications

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

Nanopharmaceuticals (part 2): products in the pipeline

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Physicochemical properties of ferumoxytol, a new intravenous iron preparation

Abstract: In vitro observations from these experiments suggest that ferumoxytol has a favourable profile in terms of tendency to release free iron, in comparison with currently available intravenous iron preparations.

Cited by 127 publications

References 27 publications

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

Nanopharmaceuticals (part 2): products in the&nbsp;pipeline

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Product

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Nanopharmaceuticals (part 2): products in the pipeline