Identification
- Summary
Ferric pyrophosphate citrate is a soluble iron compound used to maintain hemoglobin levels in patients undergoing hemodialysis.
- Brand Names
- Triferic
- Generic Name
- Ferric pyrophosphate citrate
- DrugBank Accession Number
- DB13995
- Background
Ferric pyrophosphate citrate is a soluble iron replacement product. Free iron presents several side effects as it can catalyze free radical formation and lipid peroxidation as well as the presence of interactions of iron in plasma. The ferric ion is strongly complexed by pyrophosphate and citrate.1 FPC is categorized in Japan as a second class OTC drug.6 This category is given to drugs with ingredients that in rare cases may cause health problems requiring hospitalization or worst.7 It is also FDA approved since 2015.Label
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ferric pyrophosphate citrate (DB13995)
- Weight
- Average: 1321.571
Monoisotopic: 1321.556531 - Chemical Formula
- C18H24Fe4O42P6
- Synonyms
- Ferric pyrophosphate citrate
- FPC
- SFP
- Tetraferric nonahydrogen citrate pyrophosphate
- Triferic
- External IDs
- H-61
- H61
Pharmacology
- Indication
Ferric pyrophosphate citrate is indicated for the treatment of iron loss or iron deficiency to maintain hemoglobin and to reduce the prescribed dose of erythropoiesis-stimulating agent (ESA) required to maintain desired hemoglobin levels.8
Iron deficiency appears when the dietary intake does not meet the body's requirement or when there is chronic external blood loss. During acute blood loss, body iron stores are sufficient for accelerated erythropoiesis and restoration of iron homeostasis. But when the altered homeostasis remains for weeks to months then some supplement is needed. Some causes of iron deficiency include ectoparasitism, endoparasitism, hematuria, epistaxis, hemorrhagic skin, coagulopathy, thrombocytopenia, thrombocytopathia and gastrointestinal hemorrhage.2
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- Contraindications & Blackbox Warnings
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Iron supplementation typically results in increases in serum iron, transferrin-bound iron, and iron-stored in the form of ferritin in hepatocytes and macrophages. The available iron is usually used in bone marrow for the synthesis of hemoglobin.8
- Mechanism of action
The usage of ferric pyrophosphate is based on the strong complex formation between these two species. Besides, the capacity of pyrophosphate to trigger iron removal from transferrin, enhance iron transfer from transferrin to ferritin and promote iron exchange between transferrin molecules. These properties make it a very suitable compound for parenteral administration, iron delivery into circulation and incorporation into hemoglobin.1
Target Actions Organism AFerritin light chain binderHumans AFerritin heavy chain binderHumans AHemoglobin subunit alpha binderHumans AHemoglobin subunit beta binderHumans - Absorption
The results of the present studies show that ferric pyrophosphate is as well absorbed in adults. The absorption of iron depends upon the route of entry. Ferric pyrophosphate has a very high bioavailability of 83-94%.3 The AUC and Cmax have a dose-dependent pharmacokinetic response, being of 675-1840 mcg.h/dL and 113-261 mcg/dL respectively when given in a dose from 2.5 to 10 mg. The time to reach maximum dose is approximate 4.5 hours.4
- Volume of distribution
The apparent volume of distribution of ferric pyrophosphate after 4 hours of intravenous administration ranged from 0.765 to 0.859 L.Label
- Protein binding
The main action site of ferric pyrophosphate is in the serum and thus it is highly bound to its targets such as ferritin and hemoglobin.4
- Metabolism
Metabolism of ferric pyrophosphate resembles physiological processing of iron delivered into circulation after absorption by the gut. This is suggested due to the direct ability to trigger iron transfer to transferrin, between transferrin molecules and between transferrin and ferritin without the need of prior metabolism by the reticuloendothelial system.1
- Route of elimination
After metabolism as endogenous iron, the excretion of ferric pyrophosphate follows the same pattern. In the body, iron is retained and in the absence of bleeding the excretion is very small. Most of the iron is absorbed in the gut and does not reach the feces. The excretion of iron can be done in urine, feces, sweat, hair, and nails.5
- Half-life
The half-life of ferric pyrophosphate is 1.48 hours.4
- Clearance
The mean clearance rate of ferric pyrophosphate can range between 0.406 to 0.556 L/hour.4
- Adverse Effects
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Ferric pyrophosphate was showed to be clastogenic in the in vitro chromosomal aberration assay in presence of metabolic activation. It was not showed to have mutagenic or fertility effects and its carcinogenic potential have not been studied yet.Label
- 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 softwareAluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferric ammonium citrate Ferric ammonium citrate can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferric carboxymaltose Ferric carboxymaltose can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferric cation Ferric cation can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferric maltol Ferric maltol can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferric sulfate Ferric sulfate can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferrous bisglycinate Ferrous bisglycinate can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferrous fumarate Ferrous fumarate can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferrous gluconate Ferrous gluconate can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. Ferrous succinate Ferrous succinate can cause a decrease in the absorption of Ferric pyrophosphate citrate resulting in a reduced serum concentration and potentially a decrease in efficacy. 
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- No interactions found.
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 - International/Other Brands
- Incremin (Pfizer)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Triferic Solution 5.44 mg/1mL Hemodialysis Rockwell Medical, Inc 2015-02-06 Not applicable US 
Triferic Solution 272 mg/50mL Hemodialysis; Intravenous Rockwell Medical, Inc 2015-09-04 Not applicable US Triferic Powder 272 mg/272mg Parenteral Ropack Inc. 2016-11-28 Not applicable US Triferic Powder 272 mg/1 Intravenous Rockwell Medical, Inc 2016-04-25 Not applicable US Triferic AVNU Solution 1.5 mg / mL Intravenous Rockwell Medical Inc Not applicable Not applicable Canada 
Triferic AVNU Solution 1.5 mg/1mL Intravenous Rockwell Medical Inc. 2020-03-30 Not applicable US Triferic AVNU Solution 1.5 mg/1mL Intravenous Holopack Verpackungstechnik GmgH 2020-06-02 Not applicable US Triferic Solution for Hemodialysis Solution 1.5 mg/1mL Intravenous Holopack Verpackungstechnik GmgH 2020-06-02 Not applicable US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- UBY79OCO9G
- CAS number
- 1802359-96-1
- InChI Key
- SXAWSYZURCZSDX-UHFFFAOYSA-B
- InChI
- InChI=1S/3C6H8O7.4Fe.3H4O7P2/c3*7-3(8)1-6(13,5(11)12)2-4(9)10;;;;;3*1-8(2,3)7-9(4,5)6/h3*13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;;;;3*(H2,1,2,3)(H2,4,5,6)/q;;;4*+3;;;/p-12
- IUPAC Name
- tetrairon(3+) bis((phosphonooxy)phosphonic acid) tris(2-hydroxypropane-1,2,3-tricarboxylate) (hydrogen phosphonooxy)phosphonate
- SMILES
- [Fe+3].[Fe+3].[Fe+3].[Fe+3].OP(O)(=O)OP(O)(O)=O.OP(O)(=O)OP(O)(O)=O.OP([O-])(=O)OP([O-])([O-])=O.OC(CC([O-])=O)(CC([O-])=O)C([O-])=O.OC(CC([O-])=O)(CC([O-])=O)C([O-])=O.OC(CC([O-])=O)(CC([O-])=O)C([O-])=O
References
- General References
- Gupta A, Amin NB, Besarab A, Vogel SE, Divine GW, Yee J, Anandan JV: Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis. Kidney Int. 1999 May;55(5):1891-8. doi: 10.1046/j.1523-1755.1999.00436.x. [Article]
- Naigamwalla DZ, Webb JA, Giger U: Iron deficiency anemia. Can Vet J. 2012 Mar;53(3):250-6. [Article]
- Fidler MC, Walczyk T, Davidsson L, Zeder C, Sakaguchi N, Juneja LR, Hurrell RF: A micronised, dispersible ferric pyrophosphate with high relative bioavailability in man. Br J Nutr. 2004 Jan;91(1):107-12. [Article]
- Pratt RD, Swinkels DW, Ikizler TA, Gupta A: Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers. J Clin Pharmacol. 2017 Mar;57(3):312-320. doi: 10.1002/jcph.819. Epub 2016 Oct 3. [Article]
- Underwood E. (1977). Trace elements in human and animal nutrition (4th ed.). Academic press.
- KEGG [Link]
- Nippon [Link]
- FDA Reports [Link]
- External Links
- ChemSpider
- 34994433
- ChEMBL
- CHEMBL3833317
- Wikipedia
- Iron(III)_pyrophosphate
- FDA label
- Download (336 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment End Stage Renal Disease (ESRD) 1 3 Recruiting Treatment End Stage Renal Disease (ESRD) 1 2 Not Yet Recruiting Treatment Iron Deficiency Anemia (IDA) 1 2 Terminated Treatment Iron-refractory, Iron-deficiency Anemia (IRIDA) 1 1 Completed Treatment Anemia / Chronic Kidney Disease (CKD) / Peritoneal dialysis therapy 1 1 Completed Treatment End Stage Renal Disease (ESRD) 2 1 Completed Treatment Iron-refractory, Iron-deficiency Anemia (IRIDA) 1 1, 2 Completed Treatment End Stage Renal Disease (ESRD) 4
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Powder Intravenous 272 mg/1 Powder Parenteral 272 mg/272mg Solution Hemodialysis 5.44 mg/1mL Solution Hemodialysis; Intravenous 272 mg/50mL Solution Intravenous 1.5 mg / mL Solution Intravenous 1.5 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6779468 No 2004-08-24 2016-12-31 US US7816404 No 2010-10-19 2029-04-17 US US6689275 No 2004-02-10 2016-12-31 US US7857977 No 2010-12-28 2027-09-08 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 309.6ºC at 760 mmHg 'MSDS-online' water solubility Soluble FDA label - Predicted Properties
Property Value Source Water Solubility 7.6 mg/mL ALOGPS logP -0.72 ALOGPS logP -1.3 Chemaxon logS -1.4 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 1 Chemaxon Polar Surface Area 140.62 Å2 Chemaxon Rotatable Bond Count 21 Chemaxon Refractivity 68.14 m3·mol-1 Chemaxon Polarizability 14.23 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Iron ion binding
- Specific Function
- Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a ro...
- Gene Name
- FTL
- Uniprot ID
- P02792
- Uniprot Name
- Ferritin light chain
- Molecular Weight
- 20019.49 Da
References
- Gupta A, Amin NB, Besarab A, Vogel SE, Divine GW, Yee J, Anandan JV: Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis. Kidney Int. 1999 May;55(5):1891-8. doi: 10.1046/j.1523-1755.1999.00436.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Iron ion binding
- Specific Function
- Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after ...
- Gene Name
- FTH1
- Uniprot ID
- P02794
- Uniprot Name
- Ferritin heavy chain
- Molecular Weight
- 21225.47 Da
References
- Gupta A, Amin NB, Besarab A, Vogel SE, Divine GW, Yee J, Anandan JV: Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis. Kidney Int. 1999 May;55(5):1891-8. doi: 10.1046/j.1523-1755.1999.00436.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Oxygen transporter activity
- Specific Function
- Involved in oxygen transport from the lung to the various peripheral tissues.
- Gene Name
- HBA1
- Uniprot ID
- P69905
- Uniprot Name
- Hemoglobin subunit alpha
- Molecular Weight
- 15257.405 Da
References
- Gupta A, Amin NB, Besarab A, Vogel SE, Divine GW, Yee J, Anandan JV: Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis. Kidney Int. 1999 May;55(5):1891-8. doi: 10.1046/j.1523-1755.1999.00436.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Oxygen transporter activity
- Specific Function
- Involved in oxygen transport from the lung to the various peripheral tissues.LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.Spinorphin: functions as an...
- Gene Name
- HBB
- Uniprot ID
- P68871
- Uniprot Name
- Hemoglobin subunit beta
- Molecular Weight
- 15998.34 Da
References
- Gupta A, Amin NB, Besarab A, Vogel SE, Divine GW, Yee J, Anandan JV: Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis. Kidney Int. 1999 May;55(5):1891-8. doi: 10.1046/j.1523-1755.1999.00436.x. [Article]
Drug created at February 23, 2018 20:10 / Updated at February 21, 2021 18:54