Intravenous iron, indicated for iron deficiency in adults patients with chronic kidney disease.
Initial dose is 510 mg followed by a second 510 mg intravenous injection 3 to 8 days later.
Hypersensitivity reactions reported iN 0.2% of infusions.
Adverse reactions include pruritus, rash, urticaria and wheezing occur in 3.7% of subjects.
Patients are monitored to for 30 minutes following injection to be available for treatment of hypersensitivity reactions.
There have been 79 anaphylactic reactions following intravenous injections since 2009, and patients with drug allergies should avoid this drug.
An intravenous iron preparation for treatment of the anemia of chronic kidney disease (CKD).
A carbohydrate-coated, superparamagnetic iron oxide nanoparticle.
There is little free iron present in the preparation, so that doses of 510 mg can be administered safely in as little as 17 seconds.
Studies have shown a greater proportion of both predialysis and hemodialysis patients who received ferumoxytol have hemoglobin level increases from baseline of 1 g/dl or more compared with those who received oral iron.
In a prospective, double-blind, crossover study of more than 700 patients with CKD stages 1–5 that compared the safety of ferumoxytol with normal saline injection, revealed the rates of treatment-related adverse events were 5.2% and 4.5%, respectively.
Most common adverse events occur at the injection site with bruising, pain, swelling, and erythema.
Dizziness, nausea, pruritus, headache, and fatigue occur in less than 2% of patients.
Intravenous ferumoxytol is safely and rapidly administered, and is more effective than oral iron therapy in increasing hemoglobin levels in anemic patients with CKD.
Intravenous iron therapy can decrease the required dosage of epoetin alfa in anemic patients who require hemodialysis.
CKD is an inflammatory condition, and is often associated with sequestration and impaired release of iron from macrophages of the reticuloendothelial system in the liver, spleen, and bone marrow.
This reticuloendothelial blockade causes a functional iron deficiency in which iron is present but not usable for hemoglobin synthesis.
Providing adequate bioavailable iron to correct deficits, replace ongoing losses, and overcome reticulo-endothelial blockade is required to successfully treat anemia of CKD.
The prevalence of iron deficiency in patients with CKD is 25–70%.
Oral Iron therapy may have intolerable gastrointestinal side effects, and patients my not adhere to treatments.
Hepcidin produced by the liver during CKD inhibits oral iron absorption in the small intestine, limiting bioavailability.
Iintravenous iron treatments may be required to overcome reticuloendothelial blockade and deliver sufficient quantity of iron to support erythropoiesis.
The currently available intravenous iron products—low-molecular-weight iron dextran, high-molecular-weight iron dextran, sodium f2242ic gluconate,, and iron sucrose have problems associated with their use, including arthralgias, hypotension, dyspnea, and rate-of-administration limitations.
Ferumoxytol is approved for the treatment of iron deficiency anemia in adults with CKD.
The dosage regimen is an intravenous dose of 510 mg, followed by a second dose 3–8 days later.
Ferumoxytol is given undiluted at a rate of up to 1 ml/second (30 mg/sec).
This regimen may be repeated after 1 month if the hematologic response is inadequate.
Has been studied only in adults with CKD or in healthy subjects.
A superparamagnetic iron oxide nanoparticle.
Formulation contains 30 mg of elemental iron/ml, with mannitol 44 mg/ml for isotonicity.
Ferumoxytol dosages are stated in terms of the elemental iron content.
Ferumoxytol contains or releases less free iron than other available parenteral iron preparations, and explains why ferumoxytol can safely and rapidly be administered intravenously in relatively high doses without acute adverse reactions.
After intravenous injection it is distribute throughout the intravascular compartment and is removed by phagocytes in the liver, spleen, and bone.
Iron is released intracellularly and either stored intracellularly or can be released from the cell and bound by transf2242in in the plasma.
This iron-transf2242in complex can bind to transf2242in receptors on the cell membrane of erythroid precursors, and then be internalized and subsequently incorporated into hemoglobin.
It is detected in red blood cells within 24 hours after injection.
Over half of the injected dose is detected in red blood cells 2–4 weeks after injection.
The rate of plasma clearance of parenteral iron products is dependent on their molecular weight.
The lower the molecular weight of the iron compound, the faster the plasma clearance.
Pharmaco-kinetic parameters are dose dependent, with an increasing half-life and a decreasing total body clearance as the dose increases.
It’s large molecular weight, makes the drug not dialyzable.
Associated with mild constipation, tingling, chills, gastrointestinal upset, injection-site pain, and pruritic erythematous rash.
10.6% of patients in the ferumoxytol group compared with 24% of patients in an oral iron group had adverse events related to study drug.
Among treatment-related adverse events, constipation was seen in 0.5% of ferumoxytol-treated patients and 8% of oral iron–treated patients, whereas diarrhea was seen in 1.4% of the ferumoxytol-treated patients and 5.3% of the oral iron–treated patients.
Nausea and dizziness was each seen in 1.8% of the ferumoxytol group with no reports of vomiting, whereas nausea and vomiting were seen in 4% and 2.7% of the oral iron group, respectively, with no episodes of dizziness.
In patients receiving long-term hemodialysis of greater than 90 days there were drug-related adverse events in 8.2% of the ferumoxytol group and 15.9% of the oral iron group.
In a study of patients receiving ferumoxytol or receiving 0.9% sodium chloride injection, the rate of drug-related adverse events was 5.2% after ferumoxytol administration and 4.5% after sodium chloride administration.
Adverse events were most commonly related to the injection site, including bruising, pain, swelling, warmth, erythema, and puncture-site hemorrhage, and occurred with 1.5% of the ferumoxytol doses versus 1.2% of sodium chloride doses.
The other most common drug-related adverse effects included dizziness, pruritus, headache, fatigue, and nausea, which occurs in less than 1% of patients.
With the exception of body iron status parameters, no significant biochemical changes or changes in vital signs are seen.
Trials show a regimen of intravenous ferumoxytol 510 mg for two doses over 5 ± 3 days compared with oral iron therapy of f2242ous fumarate 200 mg/day for 21 days is more effective in increasing hemoglobin levels in patients with all stages of CKD, and a greater proportion of patients have increases in hemoglobin level of 1 g/dl or more.
No direct comparisons of ferumoxytol with other parenteral iron preparations have been done.
It may be safely administered intravenously at a much more rapid rate (30 mg/sec) than currently available iron products.
With respect to other available intravenous iron preparations; a higher rate of reactions to high-molecular-weight iron dextran compared with low-molecular-weight iron dextran, sodium f2242ic gluconate, and iron sucrose.
Sodium f2242ic gluconate and iron sucrose had the lowest rate of adverse drug reactions and life-threatening events.
The incidence of major adverse drug reactions with iron sucrose and sodium f2242ic gluconate is about 2/100,000 100-mg doses of each drug administered; about 4/100,000 100-mg doses for low-molecular-weight iron dextran; and 12/100,000 100-mg doses for high-molecularweight iron dextran.
The incidence of life-threatening adverse drug reactions was 0.6, 0.9, 3.3, and 11.3/million 100-mg doses for iron sucrose, sodium f2242ic gluconate, low-molecular-weight iron dextran, and high-molecular-weight iron dextran, respectively.
The patient should be observed for adverse reactions for 30 minutes after administration of the full dose.
Has the smallest amount of free iron of all the available injectable iron preparations.