Identification

Name
Tetraferric tricitrate decahydrate
Commonly known or available as Ferric citrate
Accession Number
DB14520
Description

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
Thumb
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

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

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

TargetActionsOrganism
UIron(3+)-hydroxamate-binding protein FhuD
binder
Escherichia coli (strain K12)
ATransferrin receptor protein 1
ligand
Humans
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

Hover over products below to view reaction partners

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
Learn about our commercial Adverse Effects data.
Learn More
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

Affected organisms
Not Available
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.
DrugInteraction
Alendronic acidTetraferric tricitrate decahydrate can cause a decrease in the absorption of Alendronic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
AlmasilateAlmasilate can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy.
AluminiumAluminium can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphateAluminium 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 hydroxideAluminum hydroxide can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy.
AsenapineAsenapine can cause a decrease in the absorption of Tetraferric tricitrate decahydrate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium carbonateCalcium 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 PhosphateTetraferric 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 dihydrateTetraferric 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.
CarbidopaTetraferric tricitrate decahydrate can cause a decrease in the absorption of Carbidopa resulting in a reduced serum concentration and potentially a decrease in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Take with food.

Products

Active Moieties
NameKindUNIICASInChI Key
Ferric cationionic91O4LML61120074-52-6VTLYFUHAOXGGBS-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AuryxiaTablet, coated210 mg/1OralKeryx Biopharmaceuticals, Inc.2014-09-17Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Maxine Vitamin and Mineral SupplementTetraferric tricitrate decahydrate (8.3 mg) + Beta carotene (833.3 unit) + Biotin (50 mcg) + Calcium (166.66 mg) + Calcium ascorbate (83.3 mg) + Choline (4.16 mg) + Chromium (16.66 mcg) + Copper (.5 mg) + Cyanocobalamin (25 mcg) + Folic acid (.13 mg) + Inositol (4.16 mg) + Iodine (.025 mg) + Magnesium (83.33 mg) + Manganese (1.66 mg) + Nicotinamide (3.3 mg) + Calcium pantothenate (8.33 mg) + Potassium (16.5 mg) + Pyridoxine hydrochloride (8.33 mg) + Riboflavin (3.3 mg) + Selenium (16.66 mcg) + Thiamine hydrochloride (3.3 mg) + Vitamin A (833.3 unit) + Vitamin D (66.6 unit) + Vitamin E (66.6 unit) + Zinc (4.17 mg)TabletOralNf Formulas Inc.1988-12-312000-07-05Canada

Categories

ATC Codes
V03AE08 — Ferric citrate
Drug Categories
Classification
Not classified

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
  1. 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. [PubMed:24778671]
  2. 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. [PubMed:25053935]
  3. 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. [PubMed:23548912]
  4. Yuen HW, Becker W: Iron Toxicity . [PubMed:29083637]
  5. 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. [PubMed:1174047]
  6. Pennoyer A, Bridgeman MB: Ferric citrate (auryxia) for the treatment of hyperphosphatemia. P T. 2015 May;40(5):329-39. [PubMed:25987821]
  7. FDA Approved Drug Products: Auryxia (ferric citrate) tablets [Link]
  8. Spectrum Chemical: Ferric Citrate MSDS [Link]
ChemSpider
34993203
ChEMBL
CHEMBL3301597

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingSupportive CareChronic Kidney Disease (CKD) / End Stage Renal Disease (ESRD)1
4Active Not RecruitingSupportive CareHyperphosphataemia1
4CompletedOtherChronic Renal Failure (CRF) / End Stage Renal Disease (ESRD) / Hyperphosphataemia / Phosphorus Metabolism Disorders1
4CompletedTreatmentChronic Kidney Disease (CKD) / Iron Deficiency Anemia (IDA)1
4RecruitingNot AvailableChronic Inflammation / End Stage Renal Disease (ESRD) / Hyperphosphataemia1
3CompletedPreventionHyperphosphataemia / Renal Failure1
3CompletedTreatmentAnemia of Chronic Kidney Disease1
3CompletedTreatmentChronic Kidney Disease (CKD) / Hyperphosphataemia / Impaired kidney function / Iron Deficiency Anemia (IDA)1
3CompletedTreatmentEnd Stage Renal Disease (ESRD) / ESRD / Hyperphosphataemia1
3CompletedTreatmentEnd Stage Renal Disease (ESRD) / ESRD / Hyperphosphataemia / Renal Failure1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, coatedOral210 mg/1
TabletOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8846976No2014-09-302024-02-18Us
US8093423No2012-01-102026-04-21Us
US5753706No1998-05-192017-02-03Us
US8338642No2012-12-252024-02-18Us
US9050316No2015-06-092024-02-18Us
US8901349No2014-12-022024-02-18Us
US8754258No2014-06-172024-02-18Us
US7767851No2010-08-032024-02-18Us
US8754257No2014-06-172024-02-18Us
US8609896No2013-12-172024-02-18Us
US8299298No2012-10-302024-02-18Us
US9387191No2016-07-122030-07-21Us
US9328133No2016-05-032024-02-18Us
US9757416No2017-09-122024-02-18Us
US10300039No2019-05-282030-07-21Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.503 mg/mLALOGPS
logP1.42ALOGPS
logP-1.3ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.05ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area143.45 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity78.69 m3·mol-1ChemAxon
Polarizability13.97 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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
  1. 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. [PubMed:12046920]
  2. 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. [PubMed:2254301]
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
  1. 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. [PubMed:16564538]
  2. Geisser P, Burckhardt S: The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011 Jan 4;3(1):12-33. doi: 10.3390/pharmaceutics3010012. [PubMed:24310424]
  3. 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. [PubMed:25053935]

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
  1. 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. [PubMed:25053935]
  2. FDA Approved Drug Products: Auryxia (ferric citrate) tablets [Link]

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
  1. 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. [PubMed:24778671]
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
  1. 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. [PubMed:11005764]
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
  1. 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. [PubMed:11005764]

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
  1. 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. [PubMed:23548912]
  2. FDA Approved Drug Products: Auryxia (ferric citrate) tablets [Link]
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
  1. 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. [PubMed:23548912]
  2. FDA Approved Drug Products: Auryxia (ferric citrate) tablets [Link]

Drug created on July 12, 2018 10:50 / Updated on June 13, 2020 10:24

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates