Identification
- Summary
Ferric citrate is a phosphate binder used to control serum phosphorus levels or as an iron supplement.
- Brand Names
- Auryxia
- Generic Name
- Tetraferric tricitrate decahydrate
Commonly known or available as Ferric citrate - DrugBank Accession Number
- DB14520
- Background
Tetraferric tricitrate decahydrate is an iron containing phosphate binder used to treat hyperphosphatemia and iron deficiency anemia in adults with chronic kidney disease.6
Tetraferric tricitrate decahydrate was granted FDA approval on 5 September 2014.7
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Tetraferric tricitrate decahydrate (DB14520)
- Weight
- Average: 967.803
Monoisotopic: 967.832498 - Chemical Formula
- C18H32Fe4O31
- Synonyms
- Ferric citrate
- Ferric citrate hydrate
- External IDs
- KRX-0502
Pharmacology
- Indication
Tetraferric tricitrate decahydrate is indicated to control serum phosphorous in adults with chronic kidney disease who require dialysis.7 Tetraferric tricitrate decahydrate is also indicated to treat iron deficiency anemia in adults with chronic kidney disease who are not on dialysis.7
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- Contraindications & Blackbox Warnings
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Tetraferric tricitrate decahydrate is an iron containing product indicated to treat iron deficiency anemia and hyperphosphatemia.7 It has a wide therapeutic index, as doses can be varied significantly between patients.7 Tetraferric tricitrate decahydrate has a long duration of action in the treatment of iron deficiency anemia, due to the slow loss of iron from the body, and a moderate duration of action in the treatment of hyperphosphatemia, due to its action being dependant on residence time in the gastrointestinal tract.7 Patients should be counselled regarding the risk of iron overload.7
- Mechanism of action
Ferric (Fe3+) iron is absorbed from the gastrointestinal tract by divalent metal transporter-1, and reduced to ferrous (Fe2+) iron by ferrireductase and cytochrome b reductase 1.2 Ferrous iron is stored intracellularly in ferritin and transported into the blood by ferroportin 1.2 Transport by ferroportin 1 is coupled with oxidation to ferric iron by hephaestin or ceruloplasmin.1 Ferric iron in plasma is bound to transferrin, which carries iron to other cells.2,7 Iron is transported to mitochondria for the synthesis of heme or iron-sulfur clusters, which are integral parts of several metalloproteins like hemoglobin.1,7
Ferric iron can also bind to phosphate in the gastrointestinal tract, which precipitates as the insoluble ferric phosphate.7 Ferric phosphate remains unabsorbed and is eliminated in the feces.7 Decreased phosphate absorption gradually lowers phosphate levels in the blood.7
Target Actions Organism ATransferrin receptor protein 1 ligandHumans UIron(3+)-hydroxamate-binding protein FhuD binderEscherichia coli (strain K12) - Absorption
Ferric iron has been shown to have inferior bioavailability to ferrous iron preparations.5 Tetraferric tricitrate decahydrate has 19% the bioavailability of ferrous ascorbate.5
- Volume of distribution
Not Available
- Protein binding
Ferric iron is reduced to ferrous iron, which is carried by transferrin in serum.2,7
- Metabolism
Ferric cation is converted to ferrous iron by duodenal cytochrome B reductase.2 The heavy chain ferritin may also convert ferric iron to ferrous iron2,3
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- Route of elimination
Unabsorbed oral Tetraferric tricitrate decahydrate is eliminated in the feces.7 The absorbed iron from Tetraferric tricitrate decahydrate is generally not eliminated from the body by any route other than blood loss and exfoliation of epithelial cells.1,7
- Half-life
Not Available
- Clearance
Data regarding the clearance of iron is not readily available. However, iron loss due to exfoliation of epithelial cells is approximately 1mg/day.1
- 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.- Toxicity
Patients experiencing an overdose of iron may present with nausea, vomiting, abdominal pain, diarrhea, fluid and blood loss, hypovolemia, hematemesis, perforation, and peritonitis.4 Mild overdoses can be treated with symptomatic and supportive measures.4 More severe overdoses may require more intense treatment including chelating agents, and intravenous fluids.4 Activated charcoal is not expected to be beneficial in the case of iron overdose.4
The acute oral LD50 in rats is 1487mg/kg and in mice is 1520mg/kg.8 The acute dermal LD50 in rabbits is 2000mg/kg.8
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- 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 Integrate drug-drug
interactions in your softwareAlendronic acid Tetraferric tricitrate decahydrate can cause a decrease in the absorption of Alendronic acid resulting in a reduced serum concentration and potentially a decrease in efficacy. Almasilate Almasilate can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminium phosphate Aluminium phosphate can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Asenapine Asenapine can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium carbonate Calcium carbonate can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium Phosphate Tetraferric tricitrate decahydrate 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 Tetraferric tricitrate decahydrate can cause a decrease in the absorption of Calcium phosphate dihydrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Carbidopa Tetraferric tricitrate decahydrate can cause a decrease in the absorption of Carbidopa resulting in a reduced serum concentration and potentially a decrease in efficacy. Cefdinir Tetraferric tricitrate decahydrate can cause a decrease in the absorption of Cefdinir resulting in a reduced serum concentration and potentially a decrease in efficacy. 
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- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Ferric cation ionic 91O4LML611 20074-52-6 VTLYFUHAOXGGBS-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Auryxia Tablet, film coated 210 mg/1 Oral Akebia Therapeutics, Inc. 2014-09-17 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Maxine Vitamin and Mineral Supplement Tetraferric tricitrate decahydrate (8.3 mg / tab) + Beta carotene (833.3 unit / tab) + Biotin (50 mcg / tab) + Calcium (166.66 mg / tab) + Calcium ascorbate (83.3 mg / tab) + Choline (4.16 mg / tab) + Chromium (16.66 mcg / tab) + Copper (.5 mg / tab) + Cyanocobalamin (25 mcg / tab) + Folic acid (.13 mg / tab) + Inositol (4.16 mg / tab) + Iodine (.025 mg / tab) + Magnesium (83.33 mg / tab) + Manganese (1.66 mg / tab) + Nicotinamide (3.3 mg / tab) + Calcium pantothenate (8.33 mg / tab) + Potassium (16.5 mg / tab) + Pyridoxine hydrochloride (8.33 mg / tab) + Riboflavin (3.3 mg / tab) + Selenium (16.66 mcg / tab) + Thiamine hydrochloride (3.3 mg / tab) + Vitamin A (833.3 unit / tab) + Vitamin D (66.6 unit / tab) + Vitamin E (66.6 unit / tab) + Zinc (4.17 mg / tab) Tablet Oral Nf Formulas Inc. 1988-12-31 2000-07-05 Canada 
Categories
- ATC Codes
- V03AE08 — Ferric citrate
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Q91187K011
- CAS number
- Not Available
- InChI Key
- UISKQNNAQKPSDO-UHFFFAOYSA-E
- InChI
- InChI=1S/3C6H7O7.4Fe.10H2O/c3*7-3(8)1-6(13,5(11)12)2-4(9)10;;;;;;;;;;;;;;/h3*1-2H2,(H,7,8)(H,9,10)(H,11,12);;;;;10*1H2/q3*-1;4*+3;;;;;;;;;;/p-9
- IUPAC Name
- tetrairon(3+) tris(2-oxidopropane-1,2,3-tricarboxylate) decahydrate
- SMILES
- O.O.O.O.O.O.O.O.O.O.[Fe+3].[Fe+3].[Fe+3].[Fe+3].[O-]C(=O)CC([O-])(CC([O-])=O)C([O-])=O.[O-]C(=O)CC([O-])(CC([O-])=O)C([O-])=O.[O-]C(=O)CC([O-])(CC([O-])=O)C([O-])=O
References
- General References
- Abbaspour N, Hurrell R, Kelishadi R: Review on iron and its importance for human health. J Res Med Sci. 2014 Feb;19(2):164-74. [Article]
- Waldvogel-Abramowski S, Waeber G, Gassner C, Buser A, Frey BM, Favrat B, Tissot JD: Physiology of iron metabolism. Transfus Med Hemother. 2014 Jun;41(3):213-21. doi: 10.1159/000362888. Epub 2014 May 12. [Article]
- Pfaffen S, Abdulqadir R, Le Brun NE, Murphy ME: Mechanism of ferrous iron binding and oxidation by ferritin from a pennate diatom. J Biol Chem. 2013 May 24;288(21):14917-25. doi: 10.1074/jbc.M113.454496. Epub 2013 Apr 2. [Article]
- Yuen HW, Becker W: Iron Toxicity . [Article]
- Heinrich HC: Bioavailability of trivalent iron in oral iron preparations. Therapeutic efficacy and iron absorption from simple ferric compounds and high- or low-molecular weight ferric hydroxide-carbohydrate complexes. Arzneimittelforschung. 1975 Mar;25(3):420-6. [Article]
- Pennoyer A, Bridgeman MB: Ferric citrate (auryxia) for the treatment of hyperphosphatemia. P T. 2015 May;40(5):329-39. [Article]
- FDA Approved Drug Products: Auryxia (ferric citrate) tablets [Link]
- Spectrum Chemical: Ferric Citrate MSDS [Link]
- External Links
- ChemSpider
- 34993203
- ChEMBL
- CHEMBL3301597
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Supportive Care Chronic Kidney Disease (CKD) / End Stage Renal Disease (ESRD) 1 4 Completed Other End Stage Renal Disease (ESRD) / Hyperphosphataemia / Phosphorus Metabolism Disorders / Renal Failure, Chronic Renal Failure 1 4 Completed Supportive Care Hyperphosphataemia 1 4 Completed Treatment Chronic Kidney Disease (CKD) / Iron Deficiency Anemia (IDA) 1 4 Completed Treatment Hyperphosphataemia / Impaired Renal Function / Iron Deficiency Anemia (IDA) 1 4 Terminated Other Chronic Inflammation / End Stage Renal Disease (ESRD) / Hyperphosphataemia 1 3 Completed Prevention Hyperphosphataemia / Kidney Failure 1 3 Completed Treatment Anemia of Chronic Kidney Disease 2 3 Completed Treatment Chronic Kidney Disease (CKD) / Hyperphosphataemia / Impaired Renal Function / Iron Deficiency Anemia (IDA) 1 3 Completed Treatment End Stage Renal Disease (ESRD) / Hyperphosphataemia 4
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 210 mg/1 Syrup Oral 107.7 mg/5ml Tablet, film coated Oral 1 G Tablet Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8846976 No 2014-09-30 2024-02-18 US US8093423 No 2012-01-10 2026-04-21 US US5753706 No 1998-05-19 2017-02-03 US US8338642 No 2012-12-25 2024-02-18 US US9050316 No 2015-06-09 2024-02-18 US US8901349 No 2014-12-02 2024-02-18 US US8754258 No 2014-06-17 2024-02-18 US US7767851 No 2010-08-03 2024-02-18 US US8754257 No 2014-06-17 2024-02-18 US US8609896 No 2013-12-17 2024-02-18 US US8299298 No 2012-10-30 2024-02-18 US US9387191 No 2016-07-12 2030-07-21 US US9328133 No 2016-05-03 2024-02-18 US US9757416 No 2017-09-12 2024-02-18 US US10300039 No 2019-05-28 2030-07-21 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.503 mg/mL ALOGPS logP 1.42 ALOGPS logP -1.3 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 3.05 Chemaxon pKa (Strongest Basic) -4.2 Chemaxon Physiological Charge -3 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 143.45 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 78.69 m3·mol-1 Chemaxon Polarizability 13.97 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Virus receptor activity
- Specific Function
- Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferri...
- Gene Name
- TFRC
- Uniprot ID
- P02786
- Uniprot Name
- Transferrin receptor protein 1
- Molecular Weight
- 84870.665 Da
References
- Hemadi M, Ha-Duong NT, El Hage Chahine JM: The mechanism of iron release from the transferrin-receptor 1 adduct. J Mol Biol. 2006 May 12;358(4):1125-36. Epub 2006 Mar 13. [Article]
- Geisser P, Burckhardt S: The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011 Jan 4;3(1):12-33. doi: 10.3390/pharmaceutics3010012. [Article]
- Waldvogel-Abramowski S, Waeber G, Gassner C, Buser A, Frey BM, Favrat B, Tissot JD: Physiology of iron metabolism. Transfus Med Hemother. 2014 Jun;41(3):213-21. doi: 10.1159/000362888. Epub 2014 May 12. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Part of the ABC transporter complex FhuCDB involved in iron(3+)-hydroxamate import. Binds the iron(3+)-hydroxamate complex and transfers it to the membrane-bound permease. Required for the transpor...
- Gene Name
- fhuD
- Uniprot ID
- P07822
- Uniprot Name
- Iron(3+)-hydroxamate-binding protein FhuD
- Molecular Weight
- 32997.965 Da
References
- Clarke TE, Rohrbach MR, Tari LW, Vogel HJ, Koster W: Ferric hydroxamate binding protein FhuD from Escherichia coli: mutants in conserved and non-conserved regions. Biometals. 2002 Jun;15(2):121-31. [Article]
- Koster W, Braun V: Iron (III) hydroxamate transport into Escherichia coli. Substrate binding to the periplasmic FhuD protein. J Biol Chem. 1990 Dec 15;265(35):21407-10. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Ferric-chelate reductase that reduces Fe(3+) to Fe(2+). Present at the brush border of duodenal enterocytes where it probably reduces dietary Fe(3+) thereby facilitating its transport into the mucosal cells. Uses ascorbate as electron donor. May be involved in extracellular ascorbate recycling in erythrocyte membranes. May also act as a ferrireductase in airway epithelial cells.
- Specific Function
- Ferric-chelate reductase activity
- Gene Name
- CYBRD1
- Uniprot ID
- Q53TN4
- Uniprot Name
- Cytochrome b reductase 1
- Molecular Weight
- 31641.005 Da
References
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- 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
- TF
- Uniprot ID
- P02787
- Uniprot Name
- Serotransferrin
- Molecular Weight
- 77063.195 Da
References
- Abbaspour N, Hurrell R, Kelishadi R: Review on iron and its importance for human health. J Res Med Sci. 2014 Feb;19(2):164-74. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Virus receptor activity
- Specific Function
- Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Wil...
- Gene Name
- ITGB3
- Uniprot ID
- P05106
- Uniprot Name
- Integrin beta-3
- Molecular Weight
- 87056.975 Da
References
- Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD: Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G767-74. doi: 10.1152/ajpgi.2000.279.4.G767. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Zinc ion binding
- Specific Function
- Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently wit...
- Gene Name
- CALR
- Uniprot ID
- P27797
- Uniprot Name
- Calreticulin
- Molecular Weight
- 48141.2 Da
References
- Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD: Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G767-74. doi: 10.1152/ajpgi.2000.279.4.G767. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Zinc ion transmembrane transporter activity
- Specific Function
- Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium and lead. Involved in apical iron uptake into duodenal enterocytes. Involved in iro...
- Gene Name
- SLC11A2
- Uniprot ID
- P49281
- Uniprot Name
- Natural resistance-associated macrophage protein 2
- Molecular Weight
- 62265.195 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- May be involved in iron export from duodenal epithelial cell and also in transfer of iron between maternal and fetal circulation. Mediates iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin).
- Specific Function
- Ferrous iron transmembrane transporter activity
- Gene Name
- SLC40A1
- Uniprot ID
- Q9NP59
- Uniprot Name
- Solute carrier family 40 member 1
- Molecular Weight
- 62541.55 Da
References
Drug created at July 12, 2018 16:50 / Updated at January 08, 2021 01:07