Feraheme

Injectable Iron Supplements
Iron Supplements

For storage information, see specific product information within the How Supplied section.
Monitor serum hemoglobin, ferritin, iron, and transferrin saturation at least 1 month after the second ferumoxytol dose.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Do NOT give as an undiluted injection.

Allow at least 30 minutes between administration of ferumoxytol and medications that could potentially cause serious hypersensitivity reactions and/or hypotension such as chemotherapeutic agents or monoclonal antibodies.
Administer while the patient is in a reclined or semi-reclined position.
For patients receiving hemodialysis, administer ferumoxytol once blood pressure is stable and the patient has completed at least 1 hour of hemodialysis. Monitor for signs and symptoms of hypotension after each infusion.
Dilute in 50 to 200 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection for a final concentration of 2 to 8 mg elemental iron/mL.
Administer IV over at least 15 minutes.
Storage: Use immediately. May store at room temperature for up to 4 hours or refrigerated for up to 48 hours.

serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
acute myocardial ischemia / Early / Incidence not known
cyanosis / Early / Incidence not known
thrombosis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known

wheezing / Rapid / 3.7-3.7
hypotension / Rapid / 1.9-2.5
constipation / Delayed / 2.1-2.1
peripheral edema / Delayed / 2.0-2.0
edema / Delayed / 1.5-1.5
chest pain (unspecified) / Early / 1.3-1.3
hypertension / Early / 1.0-1.0
dyspnea / Early / 1.0-1.0
sinus tachycardia / Rapid / Incidence not known

diarrhea / Early / 4.0-4.0
rash / Early / 1.0-3.7
urticaria / Rapid / 3.7-3.7
pruritus / Rapid / 1.2-3.7
nausea / Early / 3.1-3.1
dizziness / Early / 2.6-2.6
headache / Early / 1.8-1.8
vomiting / Early / 1.5-1.5
abdominal pain / Early / 1.3-1.3
cough / Delayed / 1.3-1.3
fever / Early / 1.0-1.0
muscle cramps / Delayed / 1.0-1.0
back pain / Delayed / 1.0-1.0
syncope / Early / Incidence not known

Feraheme

Rx

Intravenous iron replacement product
Used for iron deficiency anemia in adults with chronic kidney disease
Associated with fatal and serious hypersensitivity reactions

510 mg IV every 3 to 8 days for 2 doses. Treatment may be repeated if iron deficiency persists or recurs.

Limited data indicate that ferumoxytol may be effective as an MRI contrast agent. 1 mg/kg or 1.5 mg/kg IV undiluted or diluted depending on the MR series or 4 mg/kg IV undiluted followed immediately by a saline flush have been used in magnetic resonance angiography and perfusion studies (e.g., malignant brain tumors, aortic stent-graft endoleak). One study showed that blood pool MRI using ferumoxytol resulted in more visibility of stent-graft endoleaks at 24 hours compared to CT angiography. Another study showed more accurate brain tumor perfusion assessment, with delayed enhancement 24 to 48 hours after ferumoxytol administration, compared to gadolinium.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. However, the liver is one of the main storage sites for iron, and some patients with chronic liver disease may have excessive iron storage. Administer ferumoxytol cautiously to patients with hepatic impairment.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
 

Dimercaprol: (Contraindicated) Dimercaprol forms toxic chelates with iron. These dimercaprol-iron complexes are more toxic than the metal alone, especially to the kidneys. Do not administer iron during dimercaprol treatment. Therapy with iron should generally be delayed until 24 hours after the cessation of dimercaprol therapy.
Iron: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.

Feraheme/Ferumoxytol Intravenous Inj Sol

510 mg/dose IV. Cumulative doses of 2.04 grams have been administered in clinical trials.

510 mg/dose IV. Cumulative doses of 2.04 grams have been administered in clinical trials.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Normal erythropoiesis depends on the concentration of iron and erythropoietin available in the plasma, and both are typically decreased in patients with renal failure. Exogenous administration of erythropoietin increases red blood cell production and iron utilization, contributing to iron deficiency in patients with chronic kidney disease. Ferumoxytol is a superparamagnetic iron oxide molecule coated with a polysaccharide shell. This shell aids in isolating the bioactive iron from plasma components until the iron-carbohydrate complex enters the macrophages found in the reticuloendothelial system of the liver, spleen, and bone marrow. After entering the macrophages, iron dissociates from the iron-carbohydrate complex and either enters the intracellular storage (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin. A therapeutic response to iron therapy is dependent upon the patient's iron stores and the ability to use the iron. Use of iron is influenced by the cause of the deficiency as well as other illnesses that can affect normal erythropoiesis. Iron therapy alone does not increase red blood cell production. Administration of iron only improves anemia that is associated with iron deficiency.
 
Iron-containing proteins and enzymes are important in oxidation-reduction reactions, especially those of the mitochondria. Iron is a component of myoglobin and several heme-enzymes, including the cytochromes, catalase, and peroxidase. Iron is an essential component of the metalloflavoprotein enzymes and the mitochondrial enzyme alpha-glycerophosphate oxidase. Furthermore, iron is a cofactor for enzymes such as aconitase and tryptophan pyrrolase. Iron deficiency not only causes anemia and decreased oxygen delivery, it also reduces the metabolism of muscle and decreases mitochondrial activity. Iron deficiency also can lead to defects in learning or thermoregulation. Thus, iron is important to several metabolic functions in addition to erythropoiesis.
 
Ferumoxytol has been studied as a contrast agent for magnetic resonance imaging (MRI). Because ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) with a polysaccharide coating, it can be administered via intravenous bolus without mast cell degranulation, which is an attributable property for magnetic resonance angiography and perfusion imaging. Unlike gadolinium, ferumoxytol crosses the blood brain barrier slowly and is considered a 'blood pool' agent. Ferumoxytol remains in the intravascular space and provides a longer time window for data acquisition during MRI so that data can be repeatedly acquired over a period of minutes to hours with little loss of intravascular signal intensity and minimal soft tissue enhancement.

Ferumoxytol is administered intravenously. Ferumoxytol exhibits dose-dependent, capacity-limited elimination from plasma with a half-life of approximately 15 hours. The maximum plasma concentration (Cmax) and terminal half-life of ferumoxytol increase while clearance decreases with increasing ferumoxytol dose. Volume of distribution is consistent with plasma volume.
 
Iron therapy dosage is individualized according to patient goals for serum iron concentrations, iron storage parameters (e.g., ferritin, transferrin saturation), and serum hemoglobin concentrations. Iron toxicity may occur with excessive or unnecessary iron therapy. Systemic iron is stored in ferritin and hemosiderin, which are used for future production of hemoglobin. The absorption of iron depends upon the route of administration. The tissue that first clears parenterally administered iron from the bloodstream determines the bioavailability. If the reticuloendothelial system clears iron, only small amounts will be available over time to the bone marrow. Transferrin accepts iron from the intestinal tract or from sites of storage or hemoglobin destruction. Iron, which is bound to transferrin, is then transported in plasma and distributed to the bone marrow for hemoglobin synthesis, to the reticuloendothelial system for storage, to all cells for enzymes containing iron, and to placental cells if needed to meet fetal needs. Transferrin eventually becomes available for reuse. There is no destructive metabolism of iron because it takes place in a closed system. In normal adults, ninety percent of metabolized iron is conserved and reutilized repeatedly. Very little iron is eliminated. In normal, healthy adults, some daily loss of iron occurs through normal skin, hair, and nail loss, and GI losses. Menstruating women have an increased loss as do other persons with loss of blood.

After two, 510 mg doses of ferumoxytol administered IV within 24 hours, ferumoxytol clearance was 69.1 ml/hr, volume of distribution was 3.16 L, and the Cmax and Tmax were 26 mcg/ml and 0.32 hr, respectively. Infusion rate did not affect pharmacokinetic parameters.

Fetal adverse reactions, including fetal bradycardia, have been associated with maternal hypersensitivity reactions to parenteral iron products, especially during the second and third trimester of pregnancy. Data with ferumoxytol use in human pregnancy are insufficient to inform a drug-associated risk of adverse developmental outcomes. Untreated iron deficiency anemia is associated with a risk to the mother and fetus including postpartum anemia, preterm delivery, and low birth weight. In animal studies, maternal doses equivalent to 2 times the recommended human dose during organogenesis did not result in adverse maternal or fetal effects. However, maternally toxic doses of 6 times the recommended human dose administered during organogenesis did result in decreased fetal weights and fetal malformations.

There are no data on the presence of ferumoxytol in human milk, the effects on the breast-fed child, or the effects on milk production. Ferumoxytol has been detected in the milk of lactating rats; however, the clinical relevance of this finding is not clear. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ferumoxytol and any potential adverse effects on the breast-fed child from ferumoxytol or the underlying maternal condition.