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

Details

Stereochemistry ACHIRAL
Molecular Formula C21H23N7O2S
Molecular Weight 437.518
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAZOPANIB

SMILES

CN(C1=CC2=NN(C)C(C)=C2C=C1)C3=CC=NC(NC4=CC=C(C)C(=C4)S(N)(=O)=O)=N3

InChI

InChIKey=CUIHSIWYWATEQL-UHFFFAOYSA-N
InChI=1S/C21H23N7O2S/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16/h5-12H,1-4H3,(H2,22,29,30)(H,23,24,25)

HIDE SMILES / InChI
Molecular Formula C21H23N7O2S
Molecular Weight 437.518
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 http://adisinsight.springer.com/drugs/800016874 | https://www.ncbi.nlm.nih.gov/pubmed/26767042 | https://www.ncbi.nlm.nih.gov/pubmed/17620431

Pazopanib (VOTRIENT) is an orally bioavailable multi-targeted tyrosine kinase receptor inhibitor. Pazopanib inhibits vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR) -1 and -3, cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf-MAPK/ERK (MEK)-extracellular signal-regulated kinase (ERK) pathway. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Pazopanib (VOTRIENT) was developed by GlaxoSmithKline for the treatment of solid tumours and age-related macular degeneration. However, Novartis acquired all the rights to the drug from GlaxoSmithKline. Pazopanib (VOTRIENT) is indicated for the treatment of patients with advanced renal cell carcinoma and advanced soft tissue sarcoma.

CNS Activity

Originator

Approval Year

2009
334
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8228
 0.14 µM [IC50]
Inhibitor
8228
 0.13 µM [IC50]
Inhibitor
8228
 0.146 µM [IC50]
Inhibitor
8228
 0.071 µM [IC50]
Inhibitor
8228
 0.084 µM [IC50]
Inhibitor
8228
 0.074 µM [IC50]
Inhibitor
8228
 0.43 µM [IC50]
Inhibitor
8228
 0.411 µM [IC50]
Inhibitor
8228
 0.01 µM [IC50]
Inhibitor
8228
 0.03 µM [IC50]
Inhibitor
8228
 0.047 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8360
VOTRIENT

Approved Use

VOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. VOTRIENT is a kinase inhibitor indicated for the treatment of patients with: •advanced renal cell carcinoma. (1) •advanced soft tissue sarcoma who have received prior chemotherapy. (1) Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated.

Launch Date

1.25591041E12
Primary
Approved
8360
VOTRIENT

Approved Use

VOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. VOTRIENT is a kinase inhibitor indicated for the treatment of patients with: •advanced renal cell carcinoma. (1) •advanced soft tissue sarcoma who have received prior chemotherapy. (1) Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated.

Launch Date

1.25591041E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
44.8 mg/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/31125423
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PAZOPANIB blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
50.2 mg/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/31125423
600 mg 1 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PAZOPANIB blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
58.1 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAZOPANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
821 mg × h/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/31125423
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PAZOPANIB blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
895 mg × h/L
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/31125423
600 mg 1 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PAZOPANIB blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
1037 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAZOPANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf
PAZOPANIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
PAZOPANIB
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
PAZOPANIB
Page: p. 61
Disc. AE: Proteinuria...
AEs leading to
discontinuation/dose reduction:
Proteinuria (5 patients)
Sources:
PAZOPANIB
Page: p. 61
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Disc. AE: ALT increased, AST increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (11 patient)
AST increased (11 patient)
Bilirubin increased (11 patient)
Myocardial infarction (6 patients)
Ischemic stroke (6 patients)
Transient ischemic attack (6 patients)
Fatigue (5 patients)
Diarrhea (7 patients)
Anorexia (7 patients)
Vomiting (7 patients)
Proteinuria (3 patients)
Hypertension (2 patients)
Hemorrhage (2 patients)
Confusion (12 patients)
Infection (12 patients)
Hand-and-foot syndrome (12 patients)
Edema (12 patients)
Dehydration (12 patients)
Anemia (12 patients)
Anxiety (12 patients)
Convulsion (12 patients)
Atrial fibrillation (12 patients)
Hypertension (20 patients)
Gastrointestinal disturbance (17 patients)
Liver function test abnormal (16 patients)
Fatigue (10 patients)
Hematologic disorder (4 patients)
Rash (5 patients)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
DLT: Neutropenia, Aspartate aminotransferase increased...
Other AEs: Diarrhea, Hypertension...
Dose limiting toxicities:
Neutropenia (grade 2, 1 patient)
Aspartate aminotransferase increased (grade 2, 1 patient)
Hyperbilirubinemia (grade 2, 1 patient)
Other AEs:
Diarrhea (all grades, 50%)
Hypertension (grade 3, 13%)
AST increased (grade 3, 13%)
ALT increased (all grades, 25%)
Cough (all grades, 13%)
Skin hypopigmentation (all grades, 50%)
Weight decrease (all grades, 25%)
Alopecia (all grades, 13%)
Dizziness (all grades, 13%)
Hyperbilirubinemia (all grades, 25%)
Abdominal distension (all grades, 25%)
Abdominal pain (all grades, 25%)
Fatigue (all grades, 13%)
Leukopenia (all grades, 13%)
Muscle spasms (all grades, 25%)
Upper respiratory tract infection (all grades, 13%)
Hypercholesterolemia (grade 3, 13%)
Gastrointestinal hemorrhage (grade 4, 13%)
Hypoglycemia (grade 4, 13%)
Transaminases increased (grade 4, 13%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
800 mg 1 times / day multiple, oral
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 5
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
DLT: Aspartate aminotransferase increase, Malaise...
Dose limiting toxicities:
Aspartate aminotransferase increase (grade 3, 2 patients)
Malaise (grade 3, 2 patients)
ALT increased (grade 3, 2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: advanced renal cell carcinoma
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
Other AEs: Hepatotoxicity...
Other AEs:
Hepatotoxicity (severe|grade 5)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
2000 mg 1 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
unhealthy
n = 3
Health Status: unhealthy
Population Size: 3
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
1000 mg 1 times / day multiple, oral
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
unhealthy
n = 3
Health Status: unhealthy
Population Size: 3
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
DLT: Hypertension...
Dose limiting toxicities:
Hypertension (grade 3, 1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
AEs

AEs

AESignificanceDosePopulation
Proteinuria 5 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
PAZOPANIB
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
PAZOPANIB
Page: p. 61
Fatigue 10 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
ALT increased 11 patient
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
AST increased 11 patient
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Bilirubin increased 11 patient
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Anemia 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Anxiety 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Atrial fibrillation 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Confusion 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Convulsion 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Dehydration 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Edema 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Hand-and-foot syndrome 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Infection 12 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Liver function test abnormal 16 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Gastrointestinal disturbance 17 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Hemorrhage 2 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Hypertension 2 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Hypertension 20 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Proteinuria 3 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Hematologic disorder 4 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Fatigue 5 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Rash 5 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Ischemic stroke 6 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Myocardial infarction 6 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Transient ischemic attack 6 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Anorexia 7 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Diarrhea 7 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Vomiting 7 patients
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
unhealthy, 59 years
n = 290
Health Status: unhealthy
Condition: renal cell carcinoma
Age Group: 59 years
Sex: M+F
Population Size: 290
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Page: p. 61
Alopecia all grades, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Cough all grades, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Dizziness all grades, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Fatigue all grades, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Leukopenia all grades, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Upper respiratory tract infection all grades, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
ALT increased all grades, 25%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Abdominal distension all grades, 25%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Abdominal pain all grades, 25%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Hyperbilirubinemia all grades, 25%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Muscle spasms all grades, 25%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Weight decrease all grades, 25%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Diarrhea all grades, 50%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Skin hypopigmentation all grades, 50%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Aspartate aminotransferase increased grade 2, 1 patient
DLT
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Hyperbilirubinemia grade 2, 1 patient
DLT
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Neutropenia grade 2, 1 patient
DLT
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
AST increased grade 3, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Hypercholesterolemia grade 3, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Hypertension grade 3, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Gastrointestinal hemorrhage grade 4, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Hypoglycemia grade 4, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Transaminases increased grade 4, 13%
600 mg 1 times / day multiple, oral
MTD
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 8
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
ALT increased grade 3, 2 patients
DLT
800 mg 1 times / day multiple, oral
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 5
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Aspartate aminotransferase increase grade 3, 2 patients
DLT
800 mg 1 times / day multiple, oral
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 5
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Malaise grade 3, 2 patients
DLT
800 mg 1 times / day multiple, oral
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
unhealthy, 61 years (range: 38–76 years)
n = 5
Health Status: unhealthy
Condition: Hepatocellular Carcinoma
Age Group: 61 years (range: 38–76 years)
Sex: M+F
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/21831954
Hepatotoxicity severe|grade 5
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: advanced renal cell carcinoma
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
Fatigue grade 3, 1 patient
DLT, Disc. AE
2000 mg 1 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
unhealthy
n = 3
Health Status: unhealthy
Population Size: 3
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Hypertension grade 3, 1 patient
DLT, Disc. AE
1000 mg 1 times / day multiple, oral
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
unhealthy
n = 3
Health Status: unhealthy
Population Size: 3
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022465lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_MedR.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1709

inhibitor
1579

inducer
768
inhibitor
1752
inhibitor
1837
inhibitor
1599

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1509

CYP2B6
799

CYP2C8
901

CYP2C19
1463

CYP2E1
876

P-gp
1437

UGT1A1
204

OATP1B1
781
CYP1A2
1032

CYP2C8
688

P-gp
1527
CYP2B6
538

CYP1A2
689
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C8
955
 moderate [IC50 10 uM]
weak (co-administration study)
Comment: AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%;
Page: 32.0
CYP2C19
1537
 moderate [IC50 11 uM]
no (co-administration study)
Comment: no effect
Page: 32,36
CYP3A4
1909
 moderate [IC50 11 uM]
weak (co-administration study)
Comment: pazopanib increased the AUC of CYP3A4 substrate (midazolam) by 32%; AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%;
Page: 33,37
CYP2B6
985
 moderate [IC50 15 uM]
CYP1A2
1673
 moderate [IC50 16 uM]
no (co-administration study)
Comment: no effect
Page: 32,36
CYP2E1
964
 moderate [IC50 17 uM]
CYP2D6
1875
 moderate [IC50 18 uM]
yes (co-administration study)
Comment: increased the AUC of CYP2D6 substrate (dextromethorphan) by 64%
Page: 32,37
CYP2C9
1803
 moderate [IC50 7.9 uM]
no (co-administration study)
Comment: no effect
Page: 32,36
CYP2B6
985
 moderate
CYP3A4
1909
 moderate
weak (co-administration study)
Comment: pazopanib increased the AUC of CYP3A4 substrate (midazolam) by 32%; AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%;
Page: 32,33,37
CYP1A2
1673
 no
P-gp
1626
 no
OATP1B1
796
 yes [IC50 0.79 uM]
UGT1A1
254
 yes [IC50 1.2 uM]
yes (pharmacogenomic study)
Comment: Certain UGT1A1 genotypes are associated with an increase in the risk of pazopanib induced hyperbilirubinemia.
Page: 34,4
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1709
 major
yes (co-administration study)
Comment: pazopanib AUC (0-t), Cmax, and half-life were increased 1.47, 2.21, and 2.81 fold, respectively;
Page: 32,35
CYP1A2
1032
 minor
CYP2C8
688
 minor
P-gp
1527
 yes
yes (co-administration study)
Comment: AUC(0-t) and Cmax values of pazopanib are increased by 59 and 50%, respectively, when coadministered with lapatinib;
Page: 34,35
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1632
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:71219
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71219
MolPort
MolPort-006-827-156
https://www.molport.com/shop/molecule-link/MolPort-006-827-156
Selleck Chemicals
pazopanib
http://www.selleckchem.com/products/pazopanib.html
ZINC
ZINC000011617039
http://zinc15.docking.org/substances/ZINC000011617039
eMolecules
30151586
https://www.emolecules.com/cgi-bin/more?vid=30151586
PubMed

PubMed

TitleDatePubMed
Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
2005 Mar 10
[Angiogenesis targeting in breast cancer].
2007
American Society of Clinical Oncology--43rd annual meeting. Research into therapeutics: Part 4.
2007 Aug
Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors.
2007 Feb
[Angiogenesis and renal cell carcinoma].
2007 Jul
Targeted therapy for renal cell carcinoma: a new treatment paradigm.
2007 Jul
Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity.
2007 Jul
Pazopanib: a novel multitargeted tyrosine kinase inhibitor.
2007 Mar
Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies.
2007 Mar 1
Evolving role of novel targeted agents in renal cell carcinoma.
2007 Sep
Neovascular age-related macular degeneration: potential therapies.
2008
New drugs for ovarian cancer.
2008 Feb
Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma.
2008 Feb
HER-2 positive breast cancer: what else beyond trastuzumab-based therapy?
2008 Jun
Update on novel therapeutic agents for cervical cancer.
2008 Sep
Targeted therapy in the treatment of metastatic renal cell cancer.
2009
Emerging pharmacologic therapies for wet age-related macular degeneration.
2009
Impact of anti-angiogenic treatments on metastatic renal cell carcinoma.
2009 Dec
Tyrosine kinase inhibitors and the thyroid.
2009 Dec
Synergistic proapoptotic effects of the two tyrosine kinase inhibitors pazopanib and lapatinib on multiple carcinoma cell lines.
2009 Dec 3
Apical ballooning syndrome during treatment with a vascular endothelial growth factor receptor antagonist.
2009 Jan 24
Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma.
2009 Jun 29
Tumoral angiogenesis and breast cancer.
2009 Mar
Targeted therapies in metastatic renal cancer in 2009.
2009 May
Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma.
2009 May 15
Pazopanib: an antiangiogenic drug in perspective.
2009 Nov
Selective inhibition of retinal angiogenesis by targeting PI3 kinase.
2009 Nov 17
Pazopanib for the treatment of renal cell carcinoma and other malignancies.
2009 Sep
Response to a novel multitargeted tyrosine kinase inhibitor pazopanib in metastatic Merkel cell carcinoma.
2009 Sep 10
VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation.
2009 Sep 18
Analytical control of genotoxic impurities in the pazopanib hydrochloride manufacturing process.
2009 Sep 8
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.
2010
Targeted therapies in epithelial ovarian cancer.
2010
Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.
2010 Feb 20
Pazopanib.
2010 Jan
New therapeutic strategies for renal cell carcinoma.
2010 Jan-Feb
[Antiangionic drugs in soft tissue sarcoma].
2010 Jun
Recent advances and future directions in the management of metastatic renal cell carcinoma.
2010 Mar
Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.
2010 May
Targeted therapy and hand-foot skin reaction in advanced renal cell carcinoma.
2010 May
The complexity of the complicity of mast cells in cancer.
2010 May
Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model.
2010 May 11
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors.
2010 May 5
Patents

Patents

20040242578
3
JP2011528326A
16
JP2013536243A
5
JP2013537228A
5

Sample Use Guides

In Vivo Use Guide
800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). Baseline moderate hepatic impairment – 200 mg orally once daily. Not recommended in patients with severe hepatic impairment.
Route of Administration: Oral
In Vitro Use Guide
Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 uM, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects
Substance Class Chemical
Created
by admin
on Thu Jul 06 21:30:50 UTC 2023
Edited
by admin
on Thu Jul 06 21:30:50 UTC 2023
Record UNII
7RN5DR86CK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PAZOPANIB
DASH   EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
PAZOPANIB [VANDF]
Common Name English
PAZOPANIB [EMA EPAR]
Common Name English
5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)(METHYL)AMINO)PYRIMIDIN-2-YL)AMINO)-2-METHYLBENZENESULFONAMIDE
Systematic Name English
GW786034
Code English
pazopanib [INN]
Common Name English
PAZOPANIB [MI]
Common Name English
BENZENESULFONAMIDE, 5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)METHYLAMINO)-2-PYRIMIDINYL)AMINO)-2-METHYL-
Systematic Name English
Pazopanib [WHO-DD]
Common Name English
NSC-752782
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 705819
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
NCI_THESAURUS C1967
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
EMA ASSESSMENT REPORTS VOTRIENT (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
FDA ORPHAN DRUG 383912
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
WHO-ATC L01XE11
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
WHO-VATC QL01XE11
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
LIVERTOX NBK548110
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
NCI_THESAURUS C1742
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
NDF-RT N0000175605
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
FDA ORPHAN DRUG 293809
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
Code System Code Type Description
EVMPD
SUB29175
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
ChEMBL
CHEMBL477772
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
PUBCHEM
10113978
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
NDF-RT
N0000182137
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
HSDB
8210
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
WIKIPEDIA
PAZOPANIB
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
MESH
C516667
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
DRUG CENTRAL
4118
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
NDF-RT
N0000182141
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
NDF-RT
N0000187062
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY Cytochrome P450 2C8 Inhibitors [MoA]
RXCUI
714438
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY RxNorm
NSC
752782
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
CAS
444731-52-6
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
EPA CompTox
DTXSID8048733
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
MERCK INDEX
M8430
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY Merck Index
CHEBI
71219
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
LACTMED
Pazopanib
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
FDA UNII
7RN5DR86CK
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
SMS_ID
100000090733
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
DAILYMED
7RN5DR86CK
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
DRUG BANK
DB06589
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
INN
8681
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
IUPHAR
5698
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
NCI_THESAURUS
C74547
Created by admin on Thu Jul 06 21:30:50 UTC 2023 , Edited by admin on Thu Jul 06 21:30:50 UTC 2023
PRIMARY
Related Record Type Details
OATP1B1
TRANSPORTER -> SUBSTRATE
VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2
TARGET -> INHIBITOR
Structure of PAZOPANIB HYDROCHLORIDE MONOHYDRATE
SALT/SOLVATE -> PARENT
Structure of PAZOPANIB HYDROCHLORIDE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of GSK-1268992
METABOLITE INACTIVE -> PARENT
LESS THAN 10%
PLASMA
Structure of GSK-1071306
METABOLITE INACTIVE -> PARENT
In plasma and blood, individual circulating metabolites represented less than 10% total radioactivity
PLASMA
Structure of GSK-1268997
METABOLITE ACTIVE -> PARENT
Only one of these metabolites (GSK1268997) has been shown to inhibit the proliferation of VEGF-stimulated human umbilical vein endothelial cells with potency similar to pazopanib. The other metabolites show at least 10- to 20-fold less activity than the parent compound in the same cellular assay.
Structure of GSK-1268992
METABOLITE INACTIVE -> PARENT
FECAL
Structure of GSK-1268997
METABOLITE ACTIVE -> PARENT
The majority of radiolabeled material recovered in feces constituted unchanged pazopanib, accounting for a mean of 67% of the administered radioactivity activity dose. Pazopanib metabolites GSK1268992 and GSK1268997 accounted for means of approximately 6% and 2% of the administered radioactivity dose, respectively.
FECAL
Structure of GSK-1268997
METABOLITE ACTIVE -> PARENT
Renal elimination of pazopanib is accounted for less than 4% of bodily excretion of the administered dose (Table 9). The majority of the radioactivity (82.2%) was recovered in feces by 120 hours (Table 9). Pazopanib undergoes moderate liver metabolism.
FECAL; PLASMA; URINE
Structure of GSK-1268992
METABOLITE INACTIVE -> PARENT
Four pazopanib metabolites (GSK1268992, GSK1268997, GSK1071306, and GW700201) have been identified. Only one of these metabolites (GSK1268997) has been shown to inhibit the proliferation of VEGF-stimulated human umbilical vein endothelial cells with potency similar to pazopanib. The other metabolites show at least 10- to 20-fold less activity than the parent compound in the same cellular assay.
Structure of GSK-1268992
METABOLITE INACTIVE -> PARENT
Renal elimination of pazopanib is accounted for less than 4% of bodily excretion of the administered dose (Table 9). The majority of the radioactivity (82.2%) was recovered in feces by 120 hours (Table 9). Pazopanib undergoes moderate liver metabolism. Pazopanib was the major drug-related component in human plasma representing 84% and 91% of the AUC(0-∞) in two of the three subjects that received 400 mg radiolabeled pazopanib.
FECAL; PLASMA; URINE
Structure of GSK-1071306
METABOLITE INACTIVE -> PARENT
Four pazopanib metabolites (GSK1268992, GSK1268997, GSK1071306, and GW700201) have been identified. Only one of these metabolites (GSK1268997) has been shown to inhibit the proliferation of VEGF-stimulated human umbilical vein endothelial cells with potency similar to pazopanib.
Related Record Type Details
Structure of PAZOPANIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Structure of PAZOPANIB
Elimination
PHARMACOKINETIC
NIH
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