Deferiprone

Identification

Summary

Deferiprone is an iron chelator used to treat patients with transfusional iron overload caused by thalassemia syndromes.

Brand Names
Ferriprox
Generic Name
Deferiprone
DrugBank Accession Number
DB08826
Background

Deferiprone is an oral iron chelator used as a second line agent in thalassemia syndromes when iron overload from blood transfusions occurs. Thalassemias are a type of hereditary anaemia due a defect in the production of hemoglobin. As a result, erythropoiesis, the production of new red blood cells, is impaired. FDA approved on October 14, 2011.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 139.1519
Monoisotopic: 139.063328537
Chemical Formula
C7H9NO2
Synonyms
  • 1,2-Dimethyl-3-hydroxypyrid-4-one
  • 3-Hydroxy-1,2-dimethyl-4(1H)-pyridone
  • Deferiprona
  • Défériprone
  • Deferiprone
  • Deferipronum
External IDs
  • APO-066
  • APO-66
  • CP-20
  • CP20
  • DN-180-01-AF
  • L-1

Pharmacology

Indication

Deferiprone is indicated in thalassemia syndromes when first line chelation agents are not adequate to treat transfusional iron overload.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Not Available

Mechanism of action

Deferiprone is an iron chelator that binds to ferric ions (iron III) and forms a 3:1 (deferiprone:iron) stable complex and is then eliminated in the urine. Deferiprone is more selective for iron in which other metals such as zinc, copper, and aluminum have a lower affinity for deferiprone.

Absorption

Deferiprone is absorbed in the upper gastrointestinal tract. Absorption is rapid with maximum plasma concentrations occurring after 1 hour in the fasted state and after 2 hours in the fed state.

Volume of distribution

In healthy patients, the volume of distribution is 1L/kg, and in thalassemia patients, the volume of distribution is 1.6L/kg.

Protein binding

Plasma protein binding is less than 10%.

Metabolism

Deferiprone is mainly metabolized by UGT1A6 to the 3-O-glucuronide metabolite. This metabolite cannot chelate iron.

Route of elimination

Within 5-6 hours of administration, more than 90% of deferiprone is eliminated from the plasma. 75 to 90% of deferiprone is excreted in the urine as the metabolite.

Half-life

The half-life is 1.9 hours.

Clearance

Not Available

Adverse Effects
Medicalerrors
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Toxicity

Agranulocytosis and neutropenia may occur, which can lead to fatal infections. Hepatoxicity is also possible. Most common side effects that lead to discontinuation of therapy were the gastrointestinal adverse effects (diarrhea, ulcer, nausea, gastrointestinal disturbances)

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
AbacavirAbacavir may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Deferiprone which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Deferiprone which could result in a higher serum level.
AclidiniumDeferiprone may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineDeferiprone may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Deferiprone which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Deferiprone which could result in a higher serum level.
Interactions
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Food Interactions
  • Take with or without food. Food does not affect absorption.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Deferiprone LipomedTablet, film coated500 mgOralLipomed2020-12-16Not applicableEU flag
FerriproxTablet, film coated1000 mgOralChiesi Farmaceutici S.P.A.2016-09-08Not applicableEU flag
FerriproxTablet, film coated500 mgOralChiesi Farmaceutici S.P.A.2016-09-08Not applicableEU flag
FerriproxTablet500 mgOralChiesi Canada Corp.2016-03-21Not applicableCanada flag
FerriproxSolution100 mg/1mLOralChiesi USA, Inc.2015-09-09Not applicableUS flag
FerriproxTablet, film coated500 mg/1OralApoPharma USA, Inc.2011-11-25Not applicableUS flag
FerriproxTablet, film coated1000 mgOralChiesi Farmaceutici S.P.A.2016-09-08Not applicableEU flag
FerriproxSolution100 mg/mlOralChiesi Farmaceutici S.P.A.2016-09-08Not applicableEU flag
FerriproxTablet1000 mg/1OralChiesi USA, Inc.2019-08-01Not applicableUS flag
FerriproxTablet1000 mg/1OralChiesi USA, Inc.2020-05-19Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DeferiproneTablet, coated500 mg/1OralHikma Pharmaceuticals USA Inc.2021-06-03Not applicableUS flag
DeferiproneTablet500 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2019-02-08Not applicableUS flag

Categories

ATC Codes
V03AC02 — Deferiprone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as methylpyridines. These are organic compounds containing a pyridine ring substituted at one or more positions by a methyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Methylpyridines
Direct Parent
Methylpyridines
Alternative Parents
Hydroxypyridines / Dihydropyridines / Vinylogous amides / Heteroaromatic compounds / Cyclic ketones / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Aromatic heteromonocyclic compound / Azacycle / Cyclic ketone / Dihydropyridine / Heteroaromatic compound / Hydrocarbon derivative / Hydropyridine / Hydroxypyridine / Methylpyridine / Organic nitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyridone (CHEBI:68554)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
2BTY8KH53L
CAS number
30652-11-0
InChI Key
TZXKOCQBRNJULO-UHFFFAOYSA-N
InChI
InChI=1S/C7H9NO2/c1-5-7(10)6(9)3-4-8(5)2/h3-4,10H,1-2H3
IUPAC Name
3-hydroxy-1,2-dimethyl-1,4-dihydropyridin-4-one
SMILES
CN1C=CC(=O)C(O)=C1C

References

General References
  1. Roberts DJ, Brunskill SJ, Doree C, Williams S, Howard J, Hyde CJ: Oral deferiprone for iron chelation in people with thalassaemia. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004839. [Article]
  2. Victor Hoffbrand A: Deferiprone therapy for transfusional iron overload. Best Pract Res Clin Haematol. 2005 Jun;18(2):299-317. [Article]
KEGG Drug
D07416
PubChem Compound
2972
PubChem Substance
175427107
ChemSpider
2866
RxNav
11645
ChEBI
68554
ChEMBL
CHEMBL70927
ZINC
ZINC000000006226
PharmGKB
PA166118041
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Deferiprone
AHFS Codes
  • 64:00.00 — Heavy Metal Antagonists
FDA label
Download (287 KB)
MSDS
Download (76.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableHepatic Impairment1
4CompletedNot AvailableRenal Impairment1
4CompletedTreatmentBeta Thalassemia Major Anemia / Iron Overload1
4CompletedTreatmentCardiomyopathy / Iron Overload1
4CompletedTreatmentHemosiderosis / Thalassemia Major (TM)1
4CompletedTreatmentProlonged QT Interval1
4CompletedTreatmentThalassemia Major (TM) / Β Thalassemia1
4Enrolling by InvitationTreatmentIron Overload / Other Anemias / Sickle Cell Disease (SCD)1
4RecruitingTreatmentIron Overload / Other Anemias / Sickle Cell Disease (SCD)1
4Unknown StatusTreatmentΒ Thalassemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral500 mg/1
Tablet, coatedOral500 mg/1
SolutionOral
SolutionOral100 mg/ml
SolutionOral100 mg / mL
SolutionOral100 mg/1mL
TabletOral1000 mg
TabletOral1000 mg/1
TabletOral500 mg
Tablet, coatedOral500 mg
Tablet, film coatedOral
Tablet, film coatedOral1000 mg
Tablet, film coatedOral1000 mg/1
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral500 mg
Syrup
TabletOral
Capsule250 mg
Capsule500 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7049328No2006-05-232021-06-28US flag
US8703156No2014-04-222029-10-29US flag
US10780055No2018-10-252038-10-25US flag
US10940115No2018-10-252038-10-25US flag
US10940116No2018-10-252038-10-25US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)272-278Not Available
water solubilityMaximum water solubility of 16–18 g/L at 24°Not Available
pKa3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility273.0 mg/mLALOGPS
logP-0.6ALOGPS
logP0.61ChemAxon
logS0.29ALOGPS
pKa (Strongest Acidic)11.82ChemAxon
pKa (Strongest Basic)0.52ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity40.7 m3·mol-1ChemAxon
Polarizability14.05 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9803
Blood Brain Barrier+0.9381
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.7895
P-glycoprotein inhibitor INon-inhibitor0.9143
P-glycoprotein inhibitor IINon-inhibitor0.9156
Renal organic cation transporterNon-inhibitor0.8293
CYP450 2C9 substrateNon-substrate0.7463
CYP450 2D6 substrateNon-substrate0.7407
CYP450 3A4 substrateNon-substrate0.5587
CYP450 1A2 substrateNon-inhibitor0.8281
CYP450 2C9 inhibitorNon-inhibitor0.9871
CYP450 2D6 inhibitorNon-inhibitor0.9504
CYP450 2C19 inhibitorNon-inhibitor0.982
CYP450 3A4 inhibitorNon-inhibitor0.9726
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9069
Ames testNon AMES toxic0.7697
CarcinogenicityNon-carcinogens0.9563
BiodegradationReady biodegradable0.5188
Rat acute toxicity1.8734 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9539
hERG inhibition (predictor II)Non-inhibitor0.8564
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da

Drug created on December 28, 2012 19:38 / Updated on June 23, 2021 06:08