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Details

Stereochemistry ACHIRAL
Molecular Formula C17H15BrF2N4O3
Molecular Weight 441.227
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BINIMETINIB

SMILES

Cn1cnc2c1cc(c(c2F)Nc3ccc(cc3F)Br)C(=NOCCO)O

InChI

InChIKey=ACWZRVQXLIRSDF-UHFFFAOYSA-N
InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)

HIDE SMILES / InChI

Molecular Formula C17H15BrF2N4O3
Molecular Weight 441.227
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C84865 | https://www.ncbi.nlm.nih.gov/pubmed/23635776 | https://acr.confex.com/acr/2006/webprogram/Paper5558.html

Binimetinib (MEK162) is an oral small-molecule with potential antineoplastic activity. It is a selective mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS. MEK162 at 6 mg/kg, BID combined with BEZ235 (dual PI3K/mTOR inhibitor) resulted in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. There are three ongoing Phase 3 trials with binimetinib in advanced cancer patients: NEMO (NRAS-mutant melanoma), COLUMBUS (encorafenib in combination with binimetinib in BRAF-mutant melanoma) and BEACON CRC (encorafenib, binimetinib and cetuximab in BRAF-mutant colorectal cancer).

CNS Activity

Curator's Comment:: might be able to penetrate the blood-brain barrier, which has encouraged investigators to explore this therapeutic candidate.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
545 ng/mL
60 mg 2 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BINIMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
241 ng/mL
45 mg 2 times / day multiple, oral
dose: 45 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BINIMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1710 ng × h/mL
60 mg 2 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BINIMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
964 ng × h/mL
45 mg 2 times / day multiple, oral
dose: 45 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BINIMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
DLT: Chorioretinopathy, Dermatitis acneiform...
Disc. AE: Macular oedema, Nausea...
Other AEs: Retinal deposits, Retinopathy...
Dose limiting toxicities:
Chorioretinopathy (grade 3, 25%)
Dermatitis acneiform (grade 3, 25%)
AEs leading to
discontinuation/dose reduction:
Macular oedema (grade 3-4, 25%)
Nausea (grade 1-2, 25%)
Vomiting (grade 1-2, 50%)
Fatigue (grade 1-2, 25%)
Other AEs:
Retinal deposits (grade 3-4, 25%)
Retinopathy (grade 3-4, 25%)
Papilloedema (grade 3-4, 25%)
Retinal detachment (grade 3-4, 25%)
Retinal disorder (grade 3-4, 25%)
Acne (grade 3-4, 25%)
Skin exfoliation (grade 3-4, 25%)
Diarrhoea (grade 1-2, 25%)
Peripheral oedema (grade 1-2, 50%)
Abdominal pain (grade 1-2, 25%)
Anorexia (grade 1-2, 25%)
Dyspnoea (grade 1-2, 25%)
Sources:
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Disc. AE: Dermatitis acneiform, Acne...
Other AEs: Diarrhoea, Peripheral oedema...
AEs leading to
discontinuation/dose reduction:
Dermatitis acneiform (grade 1-2, 85%)
Acne (grade 1-2, 85%)
Skin exfoliation (grade 1-2, 85%)
Dermatitis acneiform (grade 3-4, 2%)
Acne (grade 3-4, 2%)
Skin exfoliation (grade 3-4, 2%)
Nausea (grade 1-2, 51%)
Vomiting (grade 1-2, 49%)
Fatigue (grade 1-2, 39%)
Fatigue (grade 3-4, 2%)
Other AEs:
Diarrhoea (grade 1-2, 61%)
Peripheral oedema (grade 1-2, 51%)
Anaemia (grade 1-2, 12%)
Anaemia (grade 3-4, 24%)
Abdominal pain (grade 1-2, 17%)
Abdominal pain (grade 3-4, 7%)
Anorexia (grade 1-2, 20%)
Constipation (grade 1-2, 20%)
Constipation (grade 3-4, 5%)
Dyspnoea (grade 1-2, 15%)
Dyspnoea (grade 3-4, 2%)
Pyrexia (grade 1-2, 17%)
Pyrexia (grade 3-4, 2%)
Dizziness (grade 1-2, 22%)
Pulmonary embolism (grade 4, 1 patient)
Generalised oedema (grade 4, 1 patient)
Sources:
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Disc. AE: Retinal deposits, Retinopathy...
Other AEs: Papilloedema, Retinal disorder...
AEs leading to
discontinuation/dose reduction:
Retinal deposits (grade 1-2, 27%)
Retinopathy (grade 1-2, 27%)
Chorioretinopathy (grade 1-2, 27%)
Macular oedema (grade 1-2, 27%)
Retinal detachment (grade 1-2, 27%)
Other AEs:
Papilloedema (grade 1-2, 27%)
Retinal disorder (grade 1-2, 27%)
Sources:
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Disc. AE: Chorioretinopathy, Macular oedema...
Other AEs: Retinal deposits, Retinopathy...
AEs leading to
discontinuation/dose reduction:
Chorioretinopathy (grade 1-2, 11%)
Macular oedema (grade 1-2, 11%)
Retinal detachment (grade 1-2, 11%)
Dermatitis acneiform (grade 1-2, 75%)
Acne (grade 1-2, 75%)
Skin exfoliation (grade 1-2, 75%)
Dermatitis acneiform (grade 3-4, 2%)
Acne (grade 3-4, 2%)
Skin exfoliation (grade 3-4, 2%)
Nausea (grade 1-2, 61%)
Vomiting (grade 1-2, 52%)
Diarrhoea (grade 1-2, 39%)
Fatigue (grade 1-2, 41%)
Fatigue (grade 3-4, 5%)
Other AEs:
Retinal deposits (grade 1-2, 11%)
Retinopathy (grade 1-2, 11%)
Papilloedema (grade 1-2, 11%)
Retinal disorder (grade 1-2, 11%)
Peripheral oedema (grade 1-2, 45%)
Anaemia (grade 1-2, 11%)
Anaemia (grade 3-4, 7%)
Abdominal pain (grade 1-2, 16%)
Abdominal pain (grade 3-4, 2%)
Anorexia (grade 1-2, 18%)
Constipation (grade 1-2, 14%)
Dyspnoea (grade 1-2, 11%)
Dyspnoea (grade 3-4, 5%)
Pyrexia (grade 1-2, 16%)
Dizziness (grade 1-2, 11%)
Sources:
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Left ventricular dysfunction, Serous retinopathy...
Other AEs: Fatigue, Pyrexia...
AEs leading to
discontinuation/dose reduction:
Left ventricular dysfunction (6%)
Serous retinopathy (5%)
Left ventricular dysfunction (3%)
Serous retinopathy (3%)
Colitis (2%)
Hemorrhage (2%)
Headache (1%)
Other AEs:
Fatigue (grade 3-4, 3%)
Pyrexia (grade 3-4, 4%)
Peripheral edema (grade 3-4, 1%)
Fatigue (all grades, 43%)
Pyrexia (all grades, 18%)
Peripheral edema (all grades, 13%)
Nausea (grade 3-4, 2%)
Diarrhea (grade 3-4, 3%)
Vomiting (grade 3-4, 2%)
Abdominal pain (grade 3-4, 4%)
Nausea (all grades, 41%)
Diarrhea (all grades, 36%)
Vomiting (all grades, 30%)
Abdominal pain (all grades, 28%)
Constipation (all grades, 22%)
Rash (grade 3-4, 1%)
Rash (all grades, 22%)
Dizziness (grade 3-4, 3%)
Dizziness (all grades, 15%)
Visual impairment (all grades, 20%)
Serous retinopathy (grade 3-4, 3%)
Serous retinopathy (all grades, 20%)
Hemorrhage (grade 3-4, 3%)
Hemorrhage (all grades, 19%)
Hypertension (grade 3-4, 6%)
Hypertension (all grades, 11%)
Anemia (grade 3-4, 3.6%)
Anemia (all grades, 36%)
Leukopenia (all grades, 13%)
Lymphopenia (grade 3-4, 2.1%)
Lymphopenia (all grades, 13%)
Neutropenia (grade 3-4, 3.1%)
Neutropenia (all grades, 13%)
Creatinine increased (grade 3-4, 3.6%)
Creatinine increased (all grades, 93%)
Creatine phosphokinase increased (grade 3-4, 5%)
Creatine phosphokinase increased (all grades, 58%)
Gamma-glutamyltransferase increased (grade 3-4, 11%)
Gamma-glutamyltransferase increased (all grades, 45%)
ALT increased (grade 3-4, 6%)
ALT increased (all grades, 29%)
AST increased (grade 3-4, 2.6%)
AST increased (all grades, 27%)
Alkaline phosphatase increased (grade 3-4, 0.5%)
Alkaline phosphatase increased (all grades, 21%)
Hyponatremia (grade 3-4, 3.6%)
Hyponatremia (all grades, 18%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain grade 1-2, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Anorexia grade 1-2, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Diarrhoea grade 1-2, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dyspnoea grade 1-2, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Fatigue grade 1-2, 25%
Disc. AE
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Nausea grade 1-2, 25%
Disc. AE
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Peripheral oedema grade 1-2, 50%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Vomiting grade 1-2, 50%
Disc. AE
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Chorioretinopathy grade 3, 25%
DLT, Disc. AE
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dermatitis acneiform grade 3, 25%
DLT, Disc. AE
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Acne grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Papilloedema grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinal deposits grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinal detachment grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinal disorder grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinopathy grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Skin exfoliation grade 3-4, 25%
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Macular oedema grade 3-4, 25%
Disc. AE
80 mg 2 times / day steady, oral
Highest studied dose
Dose: 80 mg, 2 times / day
Route: oral
Route: steady
Dose: 80 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Anaemia grade 1-2, 12%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dyspnoea grade 1-2, 15%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Abdominal pain grade 1-2, 17%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Pyrexia grade 1-2, 17%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Anorexia grade 1-2, 20%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Constipation grade 1-2, 20%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dizziness grade 1-2, 22%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Fatigue grade 1-2, 39%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Vomiting grade 1-2, 49%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Peripheral oedema grade 1-2, 51%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Nausea grade 1-2, 51%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Diarrhoea grade 1-2, 61%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Acne grade 1-2, 85%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dermatitis acneiform grade 1-2, 85%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Skin exfoliation grade 1-2, 85%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dyspnoea grade 3-4, 2%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Pyrexia grade 3-4, 2%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Acne grade 3-4, 2%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dermatitis acneiform grade 3-4, 2%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Fatigue grade 3-4, 2%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Skin exfoliation grade 3-4, 2%
Disc. AE
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Anaemia grade 3-4, 24%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Constipation grade 3-4, 5%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Abdominal pain grade 3-4, 7%
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Generalised oedema grade 4, 1 patient
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Pulmonary embolism grade 4, 1 patient
60 mg 2 times / day steady, oral
MTD
Dose: 60 mg, 2 times / day
Route: oral
Route: steady
Dose: 60 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Papilloedema grade 1-2, 27%
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Retinal disorder grade 1-2, 27%
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Chorioretinopathy grade 1-2, 27%
Disc. AE
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Macular oedema grade 1-2, 27%
Disc. AE
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Retinal deposits grade 1-2, 27%
Disc. AE
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Retinal detachment grade 1-2, 27%
Disc. AE
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Retinopathy grade 1-2, 27%
Disc. AE
60 mg 2 times / day steady, oral
MTD
unhealthy, 58 years (range: 30–86 years)
Anaemia grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dizziness grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dyspnoea grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Papilloedema grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinal deposits grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinal disorder grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinopathy grade 1-2, 11%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Chorioretinopathy grade 1-2, 11%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Macular oedema grade 1-2, 11%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Retinal detachment grade 1-2, 11%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Constipation grade 1-2, 14%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Abdominal pain grade 1-2, 16%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Pyrexia grade 1-2, 16%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Anorexia grade 1-2, 18%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Diarrhoea grade 1-2, 39%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Fatigue grade 1-2, 41%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Peripheral oedema grade 1-2, 45%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Vomiting grade 1-2, 52%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Nausea grade 1-2, 61%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Acne grade 1-2, 75%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dermatitis acneiform grade 1-2, 75%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Skin exfoliation grade 1-2, 75%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Abdominal pain grade 3-4, 2%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Acne grade 3-4, 2%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dermatitis acneiform grade 3-4, 2%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Skin exfoliation grade 3-4, 2%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Dyspnoea grade 3-4, 5%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Fatigue grade 3-4, 5%
Disc. AE
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Anaemia grade 3-4, 7%
45 mg 2 times / day steady, oral
RP2D
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy, 58 years (range: 30–86 years)
Health Status: unhealthy
Age Group: 58 years (range: 30–86 years)
Sex: M+F
Sources:
Headache 1%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Colitis 2%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hemorrhage 2%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Left ventricular dysfunction 3%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Serous retinopathy 3%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Serous retinopathy 5%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Left ventricular dysfunction 6%
Disc. AE
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hypertension all grades, 11%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Leukopenia all grades, 13%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Lymphopenia all grades, 13%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Neutropenia all grades, 13%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Peripheral edema all grades, 13%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Dizziness all grades, 15%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hyponatremia all grades, 18%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Pyrexia all grades, 18%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hemorrhage all grades, 19%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Serous retinopathy all grades, 20%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Visual impairment all grades, 20%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Alkaline phosphatase increased all grades, 21%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Constipation all grades, 22%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Rash all grades, 22%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
AST increased all grades, 27%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Abdominal pain all grades, 28%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
ALT increased all grades, 29%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Vomiting all grades, 30%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Anemia all grades, 36%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Diarrhea all grades, 36%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Nausea all grades, 41%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Fatigue all grades, 43%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Gamma-glutamyltransferase increased all grades, 45%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Creatine phosphokinase increased all grades, 58%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Creatinine increased all grades, 93%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Alkaline phosphatase increased grade 3-4, 0.5%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Peripheral edema grade 3-4, 1%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Rash grade 3-4, 1%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Gamma-glutamyltransferase increased grade 3-4, 11%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Nausea grade 3-4, 2%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Vomiting grade 3-4, 2%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Lymphopenia grade 3-4, 2.1%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
AST increased grade 3-4, 2.6%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Diarrhea grade 3-4, 3%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Dizziness grade 3-4, 3%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Fatigue grade 3-4, 3%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hemorrhage grade 3-4, 3%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Serous retinopathy grade 3-4, 3%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Neutropenia grade 3-4, 3.1%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Anemia grade 3-4, 3.6%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Creatinine increased grade 3-4, 3.6%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hyponatremia grade 3-4, 3.6%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Abdominal pain grade 3-4, 4%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Pyrexia grade 3-4, 4%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Creatine phosphokinase increased grade 3-4, 5%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
ALT increased grade 3-4, 6%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
Hypertension grade 3-4, 6%
45 mg 2 times / day steady, oral
Recommended
Dose: 45 mg, 2 times / day
Route: oral
Route: steady
Dose: 45 mg, 2 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
weak [IC50 18.1 uM]
weak [IC50 50 uM]
weak [IC50 50 uM]
weak [IC50 >25 uM]
weak
unlikely
Comment: It is not expected for binimetinib to have a clinically relevant induction of CYP2C9, as the plasma concentrations observed in patients is well below the concentration required for minimal induction of CYP2C9 based on in vitro study
Page: -
yes [IC50 6 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
major
major
no (co-administration study)
Comment: atazanavir did not alter the exposure of BINIMETINIB
Page: -
no
no
no
no
no
no
no (co-administration study)
Comment: did not alter the exposure of midazolam
Page: -
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
MEK and the inhibitors: from bench to bedside.
2013 Apr 12
Patents

Patents

Sample Use Guides

MEK162 administered as a fixed dose of 45 mg (3 x 15 mg tablets) BID, with a glass of water and taken with or without food.
Route of Administration: Oral
MCF7 (mutant PIK3CA) breast cancer cells exhibiting sensitivity to PI3K inhibition were seeded in 12-well plates (2 × 10^4). After 24 hours, cells were treated with BEZ235, BKM120, GDC-0941, or MK2206 alone or in combination with MEK162. MEK162 (1 uM) combined with MK-2206 (2 mM) completely reversed the resistance of RSK-expressing MCF7 cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 16:37:29 UTC 2021
Edited
by admin
on Sat Jun 26 16:37:29 UTC 2021
Record UNII
181R97MR71
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BINIMETINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
5-((4-BROMO-2-FLUOROPHENYLAMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZO (D) IMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
5-((4-BROMO-2-FLUOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZIMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
BINIMETINIB [INN]
Common Name English
BINIMETINIB [USAN]
Common Name English
BINIMETINIB [JAN]
Common Name English
MEK162
Code English
ARRY-438162
Code English
MEKTOVI
Brand Name English
BINIMETINIB [MI]
Common Name English
NVP-MEK162
Code English
1H-BENZIMIDAZOLE-6-CARBOXAMIDE, 5-((4-BROMO-2-FLUOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-
Systematic Name English
ARRY-162
Code English
BINIMETINIB [ORANGE BOOK]
Common Name English
BINIMETINIB [WHO-DD]
Common Name English
5-(4-BROMO-2-FLUOROPHENYLAMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZO(D)IMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
ARRY 438162
Code English
MEK-162
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 411613
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
NCI_THESAURUS C69145
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
WHO-ATC L01XE41
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
FDA ORPHAN DRUG 411513
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
FDA ORPHAN DRUG 440414
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C84865
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
EVMPD
SUB179942
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
INN
9764
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
CAS
606143-89-9
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
DRUG CENTRAL
5290
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
MERCK INDEX
M12078
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
PUBCHEM
10288191
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
FDA UNII
181R97MR71
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
EPA CompTox
606143-89-9
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
WIKIPEDIA
Binimetinib
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
LACTMED
Binimetinib
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
ChEMBL
CHEMBL3187723
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
RXCUI
2049122
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
DRUG BANK
DB11967
Created by admin on Sat Jun 26 16:37:30 UTC 2021 , Edited by admin on Sat Jun 26 16:37:30 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> INHIBITOR
MINOR
IC50
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
MINOR
IC50
BINDER->LIGAND
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
URINE
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC DOSE

Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC DOSE