U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H15N3O4
Molecular Weight 373.3615
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEFERASIROX

SMILES

OC(=O)C1=CC=C(C=C1)N2N=C(N=C2C3=C(O)C=CC=C3)C4=C(O)C=CC=C4

InChI

InChIKey=BOFQWVMAQOTZIW-UHFFFAOYSA-N
InChI=1S/C21H15N3O4/c25-17-7-3-1-5-15(17)19-22-20(16-6-2-4-8-18(16)26)24(23-19)14-11-9-13(10-12-14)21(27)28/h1-12,25-26H,(H,27,28)

HIDE SMILES / InChI
Molecular Formula C21H15N3O4
Molecular Weight 373.3615
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17927285; https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3495a70c-870c-4968-940e-8baea152cf85; https://www.google.com/patents/US20080312302?cl=en; http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000670/WC500033929.pdf

Deferasirox (marketed as Exjade, Desirox, Deferasirox) is an iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved for this purpose in the USA by FDA in November 2005. It is approved in the European Union by the European Medicines Agency (EMA) for children 6 years and older for chronic iron overload from repeated blood transfusions. Deferasirox is highly selective for iron as Fe3+. In approximately 1-year clinical trials of patients with transfusional chronic iron overload associated with beta-thalassaemia, sickle cell disease, myelodysplastic syndrome or other rare chronic anaemias, deferasiroxhad a beneficial effect on liver iron concentrations (LIC) and serum ferritin levels. Deferasirox can cause acute renal failure, fatal in some patients and requiring dialysis in others. It was showed that most fatalities occurred in patients with multiple comorbidities in advanced stages of their hematological disorders.

CNS Activity

CNS Penetrant
2554
Curator's Comment: Deferasirox and/or its metabolites passed the blood brain barrier to a very low extent in mouse

Originator

Novartis
173
Curator's Comment: # Novartis Pharma AG

Approval Year

2005
131
Targets

Targets

Primary TargetPharmacologyConditionPotency
Chelating Agent
142
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
Approved
8429
EXJADE

Approved Use

Exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.

Launch Date

2005
Secondary
Approved
8429
EXJADE

Approved Use

Exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.

Launch Date

2005
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
220 μM
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/26093827
30 mg/kg 1 times / day multiple, oral
dose: 30 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DEFERASIROX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
46.5 μM
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/20097723
1000 mg/kg 1 times / day steady-state, oral
dose: 1000 mg/kg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEFERASIROX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3172 μM × h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/26093827
30 mg/kg 1 times / day multiple, oral
dose: 30 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DEFERASIROX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
688 μM × h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/20097723
1000 mg/kg 1 times / day steady-state, oral
dose: 1000 mg/kg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEFERASIROX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
48.556 uM*h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01709838
10 mg/kg 1 times / day steady, oral
dose: 10 mg/kg
route of administration: oral
experiment type: steady
co-administered:
DEFERASIROX plasma
Homo sapiens
6.513 uM*h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01709838
10 mg/kg 1 times / day steady, oral
dose: 10 mg/kg
route of administration: oral
experiment type: steady
co-administered:
DEFERASIROX plasma
Homo sapiens
44.652 uM*h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01709838
10 mg/kg 1 times / day steady, oral
dose: 10 mg/kg
route of administration: oral
experiment type: steady
co-administered:
DEFERASIROX plasma
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/26093827
30 mg/kg 1 times / day multiple, oral
dose: 30 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DEFERASIROX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.4 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/20097723
1000 mg/kg 1 times / day steady-state, oral
dose: 1000 mg/kg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEFERASIROX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Disc. AE: Abnormal liver function tests, Drug-induced hepatitis...
AEs leading to
discontinuation/dose reduction:
Abnormal liver function tests (2 patients)
Drug-induced hepatitis (2 patients)
Skin rash (1 patient)
Glycosuria (1 patient)
Proteinuria (1 patient)
Henoch-Schonlein purpura (1 patient)
Hyperactivity (1 patient)
Insomnia (1 patient)
Drug fever (1 patient)
Cataract (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
90 mg/kg single, oral
Overdose
Dose: 90 mg/kg
Route: oral
Route: single
Dose: 90 mg/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
unhealthy, 20 years
n = 1
Health Status: unhealthy
Age Group: 20 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Fanconi syndrome (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
30 mg/kg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
unhealthy, 23.1 years (range: 10 -51 years)
n = 30
Health Status: unhealthy
Condition: thalassemia major
Age Group: 23.1 years (range: 10 -51 years)
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
Other AEs: Gastrointestinal symptom NOS, Skin rash...
Other AEs:
Gastrointestinal symptom NOS (mild, 40%)
Skin rash (18%)
ALT increased
AST increased
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
130 mg single, intravenous
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/18508948
healthy, 30.5 years (range: 18-45 years)
n = 17
Health Status: healthy
Age Group: 30.5 years (range: 18-45 years)
Sex: M
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/18508948
Sources:
https://pubmed.ncbi.nlm.nih.gov/18508948
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, > 2 years
Health Status: unhealthy
Age Group: > 2 years
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Other AEs: Toxicity renal, Hepatotoxicity...
Other AEs:
Toxicity renal
Hepatotoxicity
Gastrointestinal hemorrhage
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
40 mg/kg single, oral
Highest studied dose
Dose: 40 mg/kg
Route: oral
Route: single
Dose: 40 mg/kg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
healthy
Health Status: healthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
60 mg/kg 1 times / day steady, oral
Overdose
Dose: 60 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Disc. AE: Hepatitis...
AEs leading to
discontinuation/dose reduction:
Hepatitis (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy
n = 1
Health Status: unhealthy
Condition: iron overloaded beta-thalassemia
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Other AEs: Diarrhea, Nausea...
Other AEs:
Diarrhea (1 patient)
Nausea (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Cataract 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Drug fever 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Glycosuria 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Henoch-Schonlein purpura 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Hyperactivity 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Insomnia 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Proteinuria 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Skin rash 1 patient
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Abnormal liver function tests 2 patients
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Drug-induced hepatitis 2 patients
Disc. AE
20 mg/kg 1 times / day steady, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, 17.1 years (range: 2 -53 years)
n = 296
Health Status: unhealthy
Age Group: 17.1 years (range: 2 -53 years)
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Fanconi syndrome 1 patient
90 mg/kg single, oral
Overdose
Dose: 90 mg/kg
Route: oral
Route: single
Dose: 90 mg/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
unhealthy, 20 years
n = 1
Health Status: unhealthy
Age Group: 20 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
Nausea 1 patient
90 mg/kg single, oral
Overdose
Dose: 90 mg/kg
Route: oral
Route: single
Dose: 90 mg/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
unhealthy, 20 years
n = 1
Health Status: unhealthy
Age Group: 20 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
Vomiting 1 patient
90 mg/kg single, oral
Overdose
Dose: 90 mg/kg
Route: oral
Route: single
Dose: 90 mg/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
unhealthy, 20 years
n = 1
Health Status: unhealthy
Age Group: 20 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28556939/
ALT increased
30 mg/kg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
unhealthy, 23.1 years (range: 10 -51 years)
n = 30
Health Status: unhealthy
Condition: thalassemia major
Age Group: 23.1 years (range: 10 -51 years)
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
AST increased
30 mg/kg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
unhealthy, 23.1 years (range: 10 -51 years)
n = 30
Health Status: unhealthy
Condition: thalassemia major
Age Group: 23.1 years (range: 10 -51 years)
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
Skin rash 18%
30 mg/kg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
unhealthy, 23.1 years (range: 10 -51 years)
n = 30
Health Status: unhealthy
Condition: thalassemia major
Age Group: 23.1 years (range: 10 -51 years)
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
Gastrointestinal symptom NOS mild, 40%
30 mg/kg 1 times / day steady, oral
Highest studied dose
Dose: 30 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
unhealthy, 23.1 years (range: 10 -51 years)
n = 30
Health Status: unhealthy
Condition: thalassemia major
Age Group: 23.1 years (range: 10 -51 years)
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/31229401
Gastrointestinal hemorrhage
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, > 2 years
Health Status: unhealthy
Age Group: > 2 years
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Hepatotoxicity
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, > 2 years
Health Status: unhealthy
Age Group: > 2 years
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Toxicity renal
20 mg/kg 1 times / day multiple, oral
Recommended
Dose: 20 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy, > 2 years
Health Status: unhealthy
Age Group: > 2 years
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Hepatitis 1 patient
Disc. AE
60 mg/kg 1 times / day steady, oral
Overdose
Dose: 60 mg/kg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg/kg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Diarrhea 1 patient
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy
n = 1
Health Status: unhealthy
Condition: iron overloaded beta-thalassemia
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Nausea 1 patient
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
unhealthy
n = 1
Health Status: unhealthy
Condition: iron overloaded beta-thalassemia
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203560Orig1s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1767
inhibitor
1852

substrate
1217
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C8
911

CYP1A2
1524

CYP2A6
707

CYP2C19
1478

CYP2E1
882

CYP3A4/5
278

OATP transporters
1

P-gp
1461
UGT1A1
418

UGT1A3
422

CYP1A1
349

CYP1A2
1054

UGT1A7
236

UGT1A9
380

MRP1
107

MRP2
205
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OATP transporters
1
 no
no (co-administration study)
Comment: no significant interaction with digoxin
Page: 32.0
P-gp
1650
 no
no (co-administration study)
Comment: no significant interaction with digoxin or cyclosporinA
Page: 33.0
CYP2C8
965
 weak [IC50 100 uM]
yes (co-administration study)
Comment: concomitant administration of deferasirox and repaglinide resulted in increased repaglinide AUC 2.3-fold and Cmax by 62%; IC50 from p26 of clnical pharmacology review
Page: 27.0
CYP1A2
1692
 weak [IC50 175 uM]
yes (co-administration study)
Comment: concomitant administration of deferasirox and theophylline resulted in a 2X increase in theophylline but not change in Cmax; IC50 from p26 of clnical pharmacology review
Page: 27.0
CYP2A6
739
 weak [IC50 200 uM]
CYP2D6
1891
 weak [IC50 200 uM]
CYP3A4/5
335
 weak [IC50 200 uM]
yes (co-administration study)
Comment: concomitant administration of deferasirox and midazolam resulted in decreased midazolam exposure by 17%
Page: 27.0
CYP2C9
1819
 weak [IC50 210 uM]
CYP2C19
1553
 weak [IC50 330 uM]
CYP2E1
970
 weak [IC50 >500 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
UGT1A3
422
 major
UGT1A1
418
 major
yes (co-administration study)
Comment: concomitant administration of deferasirox and rifampicin resulted in decreased deferasirox AUC by 44%
Page: 7.0
MRP1
107
 no
no (co-administration study)
Comment: cyclosporinA or verapamil did not affect deferasirox permeability; no significant interaction with digoxin
Page: 33.0
MRP2
205
 no
no (co-administration study)
Comment: cyclosporinA or verapamil did not affect deferasirox permeability; no significant interaction with digoxin
Page: 33.0
CYP1A1
349
 yes
CYP1A2
1054
 yes
CYP2D6
1217
 yes
UGT1A7
236
 yes
UGT1A9
380
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:49005
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:49005
MolPort
MolPort-006-392-553
https://www.molport.com/shop/molecule-link/MolPort-006-392-553
Selleck Chemicals
Deferasirox(Exjade)
http://www.selleckchem.com/products/Deferasirox(Exjade).html
ZINC
ZINC000001481815
http://zinc15.docking.org/substances/ZINC000001481815
eMolecules
10606743
https://www.emolecules.com/cgi-bin/more?vid=10606743
PubMed

PubMed

TitleDatePubMed
A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.
2007 Feb
Iron chelators ICL670 and 311 inhibit HIV-1 transcription.
2007 Oct 25
Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation.
2010 Dec
The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors.
2010 Jul-Aug
Effects of deferasirox on renal function and renal epithelial cell death.
2011 Jun 10
Comparison of various iron chelators used in clinical practice as protecting agents against catecholamine-induced oxidative injury and cardiotoxicity.
2011 Nov 18
Efficacy of Deferasirox (Exjade®) in Modulation of Iron Overload in Patients with β-Thalassemia Intermedia.
2015
Hypersensitivity reaction with deferasirox.
2015 Apr-Jun
Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload.
2015 Jun 18
Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.
2016 Jun
Patents

Patents

20070092500
1
20070116729
157
EP1556013B1
1
EP2590630B1
1
EP2621471A2
1
JP2010031022A
1
JP2010525083A
52
JP2011512383A
1
JP2013538845A
1
US 4567202 A
1
US8772503
1
WO2009067557A1
1
WO2012003987A1
1
WO2014136079A1
1

Sample Use Guides

In Vivo Use Guide
The recommended initial dose of Exjade (deferasitox) for patients 2 years of age and older is 20 mg per kg body weight orally, once daily. After commencing therapy, monitor serum ferritin monthly and adjust the dose of Exjade, if necessary, every 3-6 months based on serum ferritin trends. Make dose adjustments in steps of 5 or 10 mg per kg and tailor adjustments to the individual patient's response and therapeutic goals. In patients not adequately controlled with doses of 30 mg per kg (e.g., serum ferritin levels persistently above 2500 mcg/L and not showing a decreasing trend over time), doses of up to 40 mg per kg may be considered. Doses above 40 mg per kg are not recommended.
Route of Administration: Oral
In Vitro Use Guide
Cell proliferation was measured using the MTT assay after human DMS-53 small-cell lung carcinoma and SK-N-MC neuroepithelioma cells were treated with deferasirox for 72 hours at 37°C. Cellular growth assays demonstrated the antiproliferative activity of deferasirox against DMS-53 and SK-N-MC cell lines with IC50 values of12uM and 14uM respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:13:29 GMT 2023
Edited
by admin
on Sat Dec 16 16:13:29 GMT 2023
Record UNII
V8G4MOF2V9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DEFERASIROX
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid
Systematic Name English
BENZOIC ACID, 4-(3,5-BIS(2-HYDROXYPHENYL)-1H-1,2,4-TRIAZOL-1-YL)-
Common Name English
DEFERASIROX [VANDF]
Common Name English
ICL670A
Code English
OSVERAL
Brand Name English
ICL670
Code English
EXJADE
Brand Name English
deferasirox [INN]
Common Name English
DEFERASIROX [USAN]
Common Name English
DEFERASIROX [USP-RS]
Common Name English
DEFERASIROX [EMA EPAR]
Common Name English
JADENU SPRINKLE
Brand Name English
DEFERASIROX [HSDB]
Common Name English
DEFERASIROX [MART.]
Common Name English
ICL-670A
Code English
JADENU
Brand Name English
Deferasirox [WHO-DD]
Common Name English
DEFERASIROX [JAN]
Common Name English
DEFERASIROX [EP MONOGRAPH]
Common Name English
DEFERASIROX [ORANGE BOOK]
Common Name English
DEFERASIROX [MI]
Common Name English
ICL-670
Code English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS EXJADE (AUTHORIZED: BETA-THALASSEMIA)
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
FDA ORPHAN DRUG 161002
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
NDF-RT N0000000144
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
NCI_THESAURUS C62357
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
NDF-RT N0000175522
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
WHO-VATC QV03AC03
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
LIVERTOX NBK548039
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
WHO-ATC V03AC03
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
FDA ORPHAN DRUG 354411
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
Code System Code Type Description
NDF-RT
N0000187062
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY Cytochrome P450 2C8 Inhibitors [MoA]
INN
8193
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
PUBCHEM
214348
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
DAILYMED
V8G4MOF2V9
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
NDF-RT
N0000185506
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
SMS_ID
100000089570
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
EVMPD
SUB21981
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
WIKIPEDIA
Deferasirox
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
EPA CompTox
DTXSID1048596
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
MERCK INDEX
m4131
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY Merck Index
MESH
C415250
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
LACTMED
Deferasirox
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
CHEBI
49005
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
EU-Orphan Drug
EU/3/02/092(EXPIRED)
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in September 2016 at the end of the period of market exclusivity. On 13 March 2002, orphan designation (EU/3/02/092) was granted by the European Commissin to Novartis Europharm Limited, United Kingdom, for 4-(3,5-bis-(hydroxy-phenyl)-1,2,4)triazol-1-yl)-benzoic acid for the treatment of chronic iron overload requiring chelation therapy.
NCI_THESAURUS
C48384
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
NDF-RT
N0000182138
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY Cytochrome P450 1A2 Inhibitors [MoA]
ChEMBL
CHEMBL550348
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
RS_ITEM_NUM
1165656
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
FDA UNII
V8G4MOF2V9
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
RXCUI
614373
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY RxNorm
CAS
201530-41-8
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
HSDB
7844
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
DRUG CENTRAL
3128
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
DRUG BANK
DB01609
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
USAN
QQ-72
Created by admin on Sat Dec 16 16:13:31 GMT 2023 , Edited by admin on Sat Dec 16 16:13:31 GMT 2023
PRIMARY
Related Record Type Details
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
CYTOCHROME P450 2C8
METABOLIC ENZYME -> INHIBITOR
WEAK
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A7
METABOLIC ENZYME -> SUBSTRATE
MINOR
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 1A1
METABOLIC ENZYME -> SUBSTRATE
Structure of FERRIC CATION
TARGET->LIGAND
Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio.
BINDING
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> SUBSTRATE
MAJOR
CYTOCHROME P450 2D6
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 1A1
METABOLIC ENZYME -> INHIBITOR
WEAK
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
Structure of DEFERASIROX ACYL-.BETA.-D-GLUCURONIDE
METABOLITE -> PARENT
PLASMA; URINE
Structure of 5-HYDROXYDEFERASIROX SULFATE
METABOLITE -> PARENT
FECAL; URINE
Structure of 5'-HYDROXYDEFERASIROX
METABOLITE -> PARENT
Presumably by CYP2D6
FECAL
Structure of 5-HYDROXYDEFERASIROX
METABOLITE -> PARENT
Presumably by CYP1A
FECAL
Structure of DEFERASIROX 2-GLUCURONIDE
METABOLITE -> PARENT
URINE
Related Record Type Details
Structure of 2-(2-HYDROXYPHENYL)-4H-1,3-BENZOXAZIN-4-ONE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of 2-(3,5-BIS(2-HYDROXYPHENYL)-1H-1,2,4-TRIAZOL-1-YL)BENZOIC ACID
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of DISALICYLAMIDE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of DEFERASIROX ETHYL ESTER
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of 4-HYDRAZINOBENZOIC ACID
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of 3-(3,5-BIS(2-HYDROXYPHENYL)-1H-1,2,4-TRIAZOL-1-YL)BENZOIC ACID
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
Structure of DEFERASIROX
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
NIH
NCATS
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