Ferumoxytol is an intravenous iron replacement product used to treat iron deficiency anemia (IDA) in patients with chronic kidney disease (CKD), or in patients who are unable to tolerate or who have not responded adequately to oral iron supplementation.
- Brand Names
- Generic Name
- DrugBank Accession Number
Ferumoxytol is an intravenously administered iron preparation indicated in the EU and the US for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD) 4.
It is comprised of superparamagnetic iron oxide nanoparticles which are coated by a semi-synthetic carbohydrate shell in an isotonic, neutral pH solution that may be administered at relatively high dose by rapid intravenous injection 8.
- Small Molecule
- Approved, Investigational
- Average: 231.531
- Chemical Formula
- Ferumoxytol non-stoichiometric magnetite
- External IDs
- CODE 7228
This drug is indicated for the treatment of iron deficiency anemia in adult patients who have experienced intolerance to oral iron or have experienced an unsatisfactory response to oral iron or who have chronic kidney disease (CKD) Label.Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.
- Associated Conditions
- Contraindications & Blackbox Warnings
- Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.
The pharmacodynamic effect of ferumoxytol on hematologic indexes such as Hgb (hemoglobin), serum ferritin, and TSAT (transferrin saturation) were studied and measured as primary and secondary endpoints in clinical efficacy studies 14.
Feraheme (ferumoxytol) reached the primary endpoint with statistical significance (p<0.001) in all three trials versus oral iron 14.
Ferumoxytol has been examined as a contrast agent for magnetic resonance imaging (MRI) studies. Because ferumoxytol is a very small superparamagnetic iron oxide (USPIO) with a polysaccharide coating, it may be administered via the intravenous bolus route without mast cell degranulation, which is an attributable property for magnetic resonance angiography and perfusion imaging. Unlike gadolinium, ferumoxytol crosses the blood-brain barrier at a slow pace and is considered a 'blood pool' agent. Ferumoxytol stays in the intravascular space and offers a longer time period for data acquisition during an MRI study so that data can be repeatedly obtained over a period of several minutes to hours with only small losses of intravascular signal intensity and minimal soft tissue enhancement 17.
Iron-containing proteins and enzymes are important in oxidation-reduction reactions, particularly those in the mitochondria. Iron is a part 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. In addition, iron is a cofactor for enzymes such as aconitase and tryptophan pyrrolase. Iron deficiency cause anemia and decreased oxygen delivery. This also reduces the metabolism of muscle and decreases mitochondrial activity. Iron deficiency may also cause defects in both learning or thermoregulation. Therefore, iron is important to several metabolic functions in addition to erythropoiesis 17.
- Mechanism of action
Feraheme (ferumoxytol) is comprised of a superparamagnetic iron oxide that is coated with a carbohydrate shell, aiding in the isolation the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen and the bone marrow 17.
The iron is then released from the iron-carbohydrate complex within vesicles located in the macrophages. Iron then either enters the intracellular storage of iron (e.g., ferritin) or can be transferred to plasma transferrin for its transport to erythroid precursor cells for incorporation into hemoglobin Label.
A therapeutic response to iron therapy depends upon the individual's iron stores and ability to utilize the iron. The systemic use of iron is influenced by the cause of the deficiency in addition to the illnesses/conditions that may affect erythropoiesis. Iron therapy by itself does not increase red blood cell (RBC) production. Administration of iron improves only the anemia associated with iron deficiency 17.
Iron-containing proteins and enzymes are essential in oxidation-reduction reactions, particularly those in the mitochondria. Iron is a part of myoglobin and various heme-enzymes, including the cytochromes, catalase, and peroxidase. Iron is an important component of the metalloflavoprotein _enzymes as well as the mitochondrial enzyme _alpha-glycerophosphate oxidase. In addition, iron serves as a cofactor for enzymes such as aconitase _and tryptophan _pyrrolase. Iron deficiency leads anemia and decreased oxygen delivery, but also reduces muscle metabolism and decreases mitochondrial activity 17.
Iron deficiency may also lead to defects in both learning and body thermoregulation. Therefore, iron is imperative to several metabolic functions in addition to erythropoiesis 17.
After intravenous administration, ferumoxytol replaces iron stores with less frequent side effects compared to the use of oral iron therapy. In addition, this agent generates T1 relaxation, producing a magnetic field and enhancing T2 relaxation, thereby darkening contrast media-containing structures in magnetic resonance imaging (MRI). Due to small particle size, ferumoxytol remains in the intravascular space for a prolonged period and so may be used as a blood pool agent 9.
T1 and T2, in radiology, refer to the timing of radiofrequency pulse sequences used to make images. The timing used to create T1 images results in images which emphasize fat tissue. The timing of radiofrequency pulse sequences utilized to create T2 images results in images which emphasize fat AND water within the body 16.
Bioavailability studies were not conducted as ferumoxytol has been developed for IV administration only 7.
Iron therapy dosage is individualized according to specific goals for blood iron concentrations, iron storage parameters (e.g., ferritin, transferrin saturation), and serum hemoglobin concentrations. Iron toxicity is possible with excessive or unnecessary iron therapy. Systemic iron is stored in ferritin and hemosiderin, which are utilized for future production of hemoglobin. The absorption of iron depends on the route of administration. The tissue that first clears parenterally ingested iron from the plasma determines its bioavailability. If the reticuloendothelial system clears iron effectively, only small amounts will become available over time to the bone marrow. Transferrin accepts iron from the intestinal tract and also from sites of hemoglobin storage and destruction 17.
- Volume of distribution
The population mean estimates for volume of distribution of the central compartment (V(1)), maximum elimination rate (V(max)), and ferumoxytol concentration at which rate of metabolism would be one-half of V(max) (K(m)) were 2.71 l, 14.3 mg/hr, and 77.5 mg/L, respectively 9.
- Protein binding
Ferumoxytol metabolism is not dependent on renal function. It is removed from the circulation by the reticuloendothelial system of the liver, spleen, and bone marrow 13.
Iron, bound to transferrin, is then transported in the plasma and distributed to the bone marrow for the synthesis of hemoglobin, to the reticuloendothelial system for storage, and to all cells for enzymes containing iron, and to placental cells if needed to meet fetal needs. Transferrin eventually becomes available for recycling. In normal adults, 90% of metabolized iron is conserved and reutilized repeatedly 17.
- Route of elimination
Iron can either become a component of intracellular ferritin or be transferred to erythroid precursor cells 12.
The pharmacokinetic (PK) behavior of Feraheme has been studied in healthy subjects and in patients with stage 5D of chronic kidney disease, on hemodialysis 9.
Feraheme showed dose-dependent, capacity-limited elimination from the plasma with a half-life of approximately 15 hours in humans 9.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
The FDA has Feraheme (ferumoxytol) may cause serious hypersensitivity reactions, including anaphylaxis and/or anaphylactoid reactions. Serious hypersensitivity reactions were reported in 0.2% (3/1,726) of subjects administered Feraheme. Some other reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria or wheezing) were reported in 3.7% (63/1,726) of these subjects. It is necessary to monitor patients for signs and symptoms of hypersensitivity for at least 30 minutes following Feraheme injection and limit administration of the drug only to when personnel and therapies are readily available for the treatment of hypersensitivity reactions Label.
Ferumoxytol was not tested for carcinogenic effects. In general genotoxicity tests, ferumoxytol showed no evidence of mutagenic activity in an in vitro Ames test or clastogenic activity in either an in vitro chromosomal aberration assay or an in vivo micronucleus assay. No adverse effects on fertility were observed in animal studies. Ferumoxytol had no effect on male or female fertility or general reproductive function in rats Label.
Feraheme may cause significant hypotension. In a clinical study with Feraheme in patients with IDA, regardless of etiology, moderate hypotension was reported in 0.2% of subjects receiving Feraheme administered as intravenous infusion for at least 15 minutes Label.
Excessive therapy with parenteral iron may lead to excess storage of iron with a possibility of iatrogenic hemosiderosis. Frequently monitor the hematologic response during parenteral iron therapy. It is advised not to administer Feraheme to patients with iron overload Label.
A note on MRI studies
Administration of Feraheme may transiently affect the diagnostic ability of MR imaging. Anticipated MR imaging studies should be done before the administration of Feraheme. Alteration of MRI imaging studies may persist for up to 12 weeks after the last Feraheme dose Label.
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Calcium Phosphate Ferumoxytol can cause a decrease in the absorption of Calcium Phosphate resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium phosphate dihydrate Ferumoxytol can cause a decrease in the absorption of Calcium phosphate dihydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Carbidopa Ferumoxytol can cause a decrease in the absorption of Carbidopa resulting in a reduced serum concentration and potentially a decrease in efficacy. Cinoxacin Ferumoxytol can cause a decrease in the absorption of Cinoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy. Ciprofloxacin Ferumoxytol can cause a decrease in the absorption of Ciprofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy. Deferiprone The serum concentration of Deferiprone can be decreased when it is combined with Ferumoxytol. Delafloxacin Ferumoxytol can cause a decrease in the absorption of Delafloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy. Dimercaprol Dimercaprol may increase the nephrotoxic activities of Ferumoxytol. Dipotassium phosphate Ferumoxytol can cause a decrease in the absorption of Dipotassium phosphate resulting in a reduced serum concentration and potentially a decrease in efficacy. Enoxacin Ferumoxytol can cause a decrease in the absorption of Enoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more
- Food Interactions
- No interactions found.
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- Active Moieties
Name Kind UNII CAS InChI Key Iron unknown E1UOL152H7 7439-89-6 XEEYBQQBJWHFJM-UHFFFAOYSA-N
- International/Other Brands
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Feraheme Solution 30 mg / mL Intravenous Amag Pharmaceuticals Inc 2012-05-01 2016-09-26 Feraheme Injection 510 mg/17mL Intravenous AMAG Pharmaceuticals, Inc. 2009-07-13 Not applicable Feridex Solution 11.2 mg/1mL Intravenous Bayer 2008-03-10 Not applicable
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ferumoxytol Injection 510 mg/17mL Intravenous Sandoz Inc 2021-07-15 Not applicable
- Drug Categories
- Compounds used in a research, industrial, or household setting
- Ferric Compounds
- Ferrous Compounds
- Hematologic Agents
- Iron Compounds
- Magnetic Resonance Contrast Activity
- Organometallic Compounds
- Paramagnetic Contrast Agent
- Parenteral Iron Replacement
- Parenteral Nutrition Solutions
- Pharmaceutical Preparations
- Pharmaceutical Solutions
- Not classified
- Affected organisms
- Humans and other mammals
- CAS number
- InChI Key
- IUPAC Name
- diiron(3+) lambda2-iron(2+) tetraoxidandiide
- General References
- Neuwelt EA, Varallyay CG, Manninger S, Solymosi D, Haluska M, Hunt MA, Nesbit G, Stevens A, Jerosch-Herold M, Jacobs PM, Hoffman JM: The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. Neurosurgery. 2007 Apr;60(4):601-11; discussion 611-2. [Article]
- Landry R, Jacobs PM, Davis R, Shenouda M, Bolton WK: Pharmacokinetic study of ferumoxytol: a new iron replacement therapy in normal subjects and hemodialysis patients. Am J Nephrol. 2005 Jul-Aug;25(4):400-10. Epub 2005 Jul 28. [Article]
- Schwenk MH: Ferumoxytol: a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease. Pharmacotherapy. 2010 Jan;30(1):70-9. doi: 10.1592/phco.30.1.70. [Article]
- McCormack PL: Ferumoxytol: in iron deficiency anaemia in adults with chronic kidney disease. Drugs. 2012 Oct 22;72(15):2013-22. doi: 10.2165/11209880-000000000-00000. [Article]
- Feraheme Product Info [Link]
- FDA Orders Stricter Warnings for Ferumoxytol (Feraheme ) [Link]
- EMA label [Link]
- Ferumoxytol [Link]
- Ferumoxytol pubChem [Link]
- Plasma Pharmacokinetics of Two Consecutive Doses of Ferumoxytol in Healthy Subjects [Link]
- Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging [Link]
- Ferumoxytol, Davisplus [Link]
- Ferumoxytol-Enhanced Magnetic Resonance Imaging in Late-Stage CKD [Link]
- Feraheme-ferumoxytol [Link]
- Cardiovascular magnetic resonance T2* for tissue iron assessment in the heart [Link]
- T1 and T2 images, Radiology Masterclass [Link]
- Feraheme PDR [Link]
- FDA label
- Download (97.6 KB)
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Iron Deficiency Anemia (IDA) 1 4 Completed Treatment Chronic Kidney Disease (CKD) / Iron Deficiency Anemia Treatment 1 4 Completed Treatment Inflammation / Iron Deficiency Anemia (IDA) / Stress Oxidative 1 4 Enrolling by Invitation Diagnostic Osteonecrosis 1 4 Recruiting Diagnostic Pediatric Congenital Heart Disease 1 4 Recruiting Treatment Anemia 1 4 Recruiting Treatment Anemia of Pregnancy / Iron Deficiency Anemia (IDA) / Pregnancy Related 1 4 Recruiting Treatment Heavy Menstrual Bleeding / Iron Deficiency Anemia (IDA) 1 3 Active Not Recruiting Treatment Iron Deficiency Anemia of Pregnancy 1 3 Completed Treatment Anemia 3
- Not Available
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 510 mg/17mL Solution Intravenous 30 mg / mL Solution Intravenous 11.2 mg/1mL Injection, solution Intravenous 30 MG/ML
- Not Available
Patent Number Pediatric Extension Approved Expires (estimated) Region US8501158 No 2013-08-06 2020-03-08 US8591864 No 2013-11-26 2020-03-08 US6599498 No 2003-07-29 2023-06-30 US7553479 No 2009-06-30 2020-03-08 US7871597 No 2011-01-18 2020-03-08 US8926947 No 2015-01-06 2020-03-08
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source logP -0.77 ChemAxon pKa (Strongest Acidic) 4.58 ChemAxon Physiological Charge 2 ChemAxon Hydrogen Acceptor Count 0 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 0 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 0 m3·mol-1 ChemAxon Polarizability 1.78 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.893 Blood Brain Barrier + 0.9831 Caco-2 permeable - 0.5852 P-glycoprotein substrate Non-substrate 0.8626 P-glycoprotein inhibitor I Non-inhibitor 0.9243 P-glycoprotein inhibitor II Non-inhibitor 0.979 Renal organic cation transporter Non-inhibitor 0.9406 CYP450 2C9 substrate Non-substrate 0.8648 CYP450 2D6 substrate Non-substrate 0.8885 CYP450 3A4 substrate Non-substrate 0.7664 CYP450 1A2 substrate Non-inhibitor 0.8662 CYP450 2C9 inhibitor Non-inhibitor 0.8859 CYP450 2D6 inhibitor Non-inhibitor 0.9369 CYP450 2C19 inhibitor Non-inhibitor 0.8911 CYP450 3A4 inhibitor Non-inhibitor 0.9708 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9446 Ames test Non AMES toxic 0.5943 Carcinogenicity Carcinogens 0.6372 Biodegradation Ready biodegradable 0.7981 Rat acute toxicity 2.4005 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9107 hERG inhibition (predictor II) Non-inhibitor 0.9799
- Mass Spec (NIST)
- Not Available
- Not Available
- Pharmacological action
- General Function
- Transferrin receptor binding
- Specific Function
- Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from si...
- Gene Name
- Uniprot ID
- Uniprot Name
- Molecular Weight
- 77063.195 Da
- EMA label [Link]
Drug created at March 19, 2008 16:17 / Updated at October 07, 2021 12:08