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Details

Stereochemistry ABSOLUTE
Molecular Formula C53H83NO14
Molecular Weight 958.2265
Optical Activity UNSPECIFIED
Defined Stereocenters 15 / 15
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EVEROLIMUS

SMILES

C[C@]1([H])/C(/[H])=C(\[H])/C(/[H])=C(\[H])/C(/[H])=C(\C)/[C@]([H])(C[C@]2([H])CC[C@@]([H])(C)[C@@](C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O[C@@]([H])(CC(=O)[C@]([H])(C)/C(/[H])=C(\C)/[C@]([H])([C@]([H])(C(=O)[C@]([H])(C)C1)OC)O)[C@]([H])(C)C[C@]4([H])CC[C@]([H])([C@@]([H])(C4)OC)OCCO)(O)O2)OC

InChI

InChIKey=HKVAMNSJSFKALM-GKUWKFKPSA-N
InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf

Everolimus is a derivative of Rapamycin (sirolimus), it is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake. Everolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. Everolimus is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and as Afinitor (general tumours) and Votubia (tumours as a result of TSC) in oncology. Everolimus is also available from Biocon, with the brand name Evertor, from Natco Pharma, with the brand name Temonat, from Ranbaxy Laboratories, with the brand name of Imozide, from Emcure Pharmaceuticals, with the brand name of Temcure, among over 20 different brands.

CNS Activity

Curator's Comment:: It has been shown that everolimus has increased CNS penetration compared with rapamycin

Originator

Curator's Comment:: # Novartis; University of Michigan Comprehensive Cancer Center

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
13.5 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AFINITOR

Approved Use

AFINITOR is a kinase inhibitor indicated for the treatment of: postmenopausal women with advanced hormone receptor-positive, HER2­ negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Launch Date

1.23828476E12
Primary
AFINITOR

Approved Use

AFINITOR is a kinase inhibitor indicated for the treatment of: postmenopausal women with advanced hormone receptor-positive, HER2­ negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Launch Date

1.23828476E12
Primary
AFINITOR

Approved Use

AFINITOR is a kinase inhibitor indicated for the treatment of: postmenopausal women with advanced hormone receptor-positive, HER2­ negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Launch Date

1.23828476E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
61.5 ng/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
EVEROLIMUS blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
18.84 ng/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EVEROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
435 ng × h/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
EVEROLIMUS blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
45.74 h
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EVEROLIMUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
27%
EVEROLIMUS plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
DLT: Rash, Mucositis...
Other AEs: Fatigue, Phosphatase alkaline increased...
Dose limiting toxicities:
Rash (grade 3, 2.9%)
Mucositis (grade 3, 1.4%)
Other AEs:
Fatigue (grade 3, 1.4%)
Phosphatase alkaline increased (grade 3, 1.4%)
Hypoalbuminemia (grade 3, 1.4%)
Hypersensitivity (grade 3, 2.9%)
Thrombocytopenia (grade 3, 2.9%)
AST increased (grade 3, 1.4%)
Hyperbilirubinemia (grade 3, 1.4%)
Anorexia (grade 3, 1.4%)
Dehydration (grade 3, 1.4%)
Dyspnea (grade 3, 2.9%)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 6
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 6
Sources:
Other AEs: Hypersensitivity...
Other AEs:
Hypersensitivity (grade 3, 16.7%)
Sources:
50 mg 1 times / week multiple, oral
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 7
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 7
Sources:
DLT: Hypokalemia...
Other AEs: Anemia, Hypersensitivity...
Dose limiting toxicities:
Hypokalemia (grade 3, 2%)
Other AEs:
Anemia (grade 3, 2%)
Hypersensitivity (grade 3, 2%)
Hyperbilirubinemia (grade 3, 2%)
Sources:
10 mg 1 times / day multiple, oral
MTD|Highest studied dose
unhealthy, median age 51 years
n = 5
Health Status: unhealthy
Condition: neuroendocrine tumors
Age Group: median age 51 years
Sex: M+F
Population Size: 5
Sources:
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
DLT: Neutropenia, Febrile neutropenia...
Other AEs: Neutropenia, Leukopenia...
Dose limiting toxicities:
Neutropenia (grade 3, 25%)
Febrile neutropenia (grade 4, 25%)
Other AEs:
Neutropenia (grade 3, 50%)
Leukopenia (grade 3, 50%)
Anemia (grade 3, 25%)
Sources:
50 mg 1 times / week multiple, oral
MTD
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 3
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 3
Sources:
20 mg 1 times / week multiple, oral
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 7
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 7
Sources:
DLT: Interstitial pneumonitis...
Dose limiting toxicities:
Interstitial pneumonitis (grade 2, 14.3%)
Sources:
35 mg 1 times / week multiple, oral (mean)
Dose: 35 mg, 1 times / week
Route: oral
Route: multiple
Dose: 35 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 10
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 10
Sources:
Other AEs: Dermatitis, Oesophagitis...
Other AEs:
Dermatitis (grade 3, 20%)
Oesophagitis (grade 3, 10%)
Asthenia (grade 3, 10%)
Sources:
20 mg 1 times / week multiple, oral
Recommended
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 5
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 5
Sources:
Other AEs: Neutropenia, Leukopenia...
Other AEs:
Neutropenia (grade 3, 80%)
Leukopenia (grade 3, 20%)
Anemia (grade 3, 20%)
Hypokalemia (grade 3, 40%)
Sources:
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
DLT: Neutropenia, Neutropenia...
Other AEs: Neutropenia, Leukopenia...
Dose limiting toxicities:
Neutropenia (grade 3, 15%)
Neutropenia (grade 4, 7%)
Febrile neutropenia (grade 4, 7%)
Other AEs:
Neutropenia (grade 3, 62%)
Leukopenia (grade 3, 15%)
Thrombocytopenia (grade 3, 23%)
Anemia (grade 3, 23%)
Febrile neutropenia (grade 3, 15%)
Hypokalemia (grade 3, 23%)
Sources:
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Disc. AE: Pneumonitis, Dyspnea...
Other AEs: Stomatitis, Anemia...
AEs leading to
discontinuation/dose reduction:
Pneumonitis (2.6%)
Dyspnea (1.9%)
Lung disorder (1.5%)
Fatigue (1.1%)
Renal failure (0.4%)
Stomatitis (4.5%)
Pneumonitis (3.3%)
Dyspnea (3%)
Mucosal inflammation (3%)
Asthenia (2.2%)
Pneumonia (2.2%)
Thrombocytopenia (2.2%)
Anemia (1.9%)
Diarrhea (1.9%)
Rash (1.5%)
Pyrexia (1.5%)
Vomiting (1.1%)
Dehydration (1.1%)
Blood creatinine increased (1.1%)
Constipation (1.1%)
Fatigue (1.1%)
Interstitial lung disease (1.1%)
Nausea (1.1%)
Abdominal pain (0.7%)
Anorexia (0.7%)
Arthralgia (0.7%)
Edema peripheral (0.7%)
Pruritus (0.7%)
Pleural effusion (0.4%)
Other AEs:
Stomatitis (grade 3, 3.3%)
Anemia (grade 3, 4.5%)
Thrombocytopenia (grade 3, 1.1%)
Lymphopenia (grade 3, 1.5%)
Platelet count decreased (grade 3, 0.4%)
Rash (grade 3, 0.7%)
Erythema (grade 3, 0.7%)
Hypercholesterolemia (grade 3, 1.9%)
Hypertriglyceridemia (grade 3, 0.7%)
Hyperglycemia (grade 3, 2.2%)
Hyperlipidemia (grade 3, 0.4%)
Blood glucose increased (grade 3, 0.7%)
Blood triglycerides increased (grade 3, 0.7%)
Diabetes mellitus (grade 3, 1.1%)
Pancreatitis acute (grade 4, 0.4%)
Blood creatinine increased (grade 3, 0.4%)
Renal failure (grade 3, 0.7%)
Renal failure acute (grade 4, 0.4%)
Pneumonitis (grade 3, 2.6%)
Interstitial lung disease (grade 3, 0.4%)
Lung infiltration (grade 3, 0.7%)
Pulmonary alveolar hemorrhage (grade 3, 0.4%)
Deep vein thrombosis (grade 3, 0.4%)
AST increased (grade 3, 0.7%)
ALT increased (grade 3, 0.4%)
Hepatic failure (grade 3, 0.4%)
Diarrhea (grade 3, 1.5%)
Dry skin (grade 3, 0.4%)
Pruritus (grade 3, 0.4%)
Palmar-plantar erythrodysaesthesia syndrome (grade 3, 0.4%)
Fatigue (grade 3, 3%)
Asthenia (grade 3, 1.5%)
Mucosal inflammation (grade 3, 1.1%)
Anorexia (grade 3, 0.4%)
Dyspnea (grade 3, 1.5%)
Infection (grade 3, 2.2%)
Infection (grade 4, 1.1%)
Hemoglobin decreased (grade 3, 8.9%)
Hemoglobin decreased (grade 4, 0.4%)
Alkaline phosphatase increased (grade 3, 0.7%)
Phosphate decreased (grade 3, 4.5%)
Sodium decreased (grade 3, 0.4%)
Calcium increased (grade 3, 0.4%)
Bilirubin increased (grade 3, 0.7%)
Bilirubin increased (grade 4, 0.4%)
Sodium increased (grade 3, 0.4%)
Sources:
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 6
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 6
Sources:
DLT: Interstitial pneumonitis...
Dose limiting toxicities:
Interstitial pneumonitis (grade 2, 16.7%)
Sources:
5 mg 1 times / day multiple, oral
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 5
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 5
Sources:
DLT: Oesophagitis, Interstitial pneumonitis...
Other AEs: Dysphagia...
Dose limiting toxicities:
Oesophagitis (grade 3, 20%)
Interstitial pneumonitis (grade 3, 20%)
Dyspnoea (grade 4, 20%)
Other AEs:
Dysphagia (grade 3)
Sources:
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
DLT: Neutropenia, Febrile neutropenia...
Other AEs: Neutropenia, Leukopenia...
Dose limiting toxicities:
Neutropenia (grade 3, 17%)
Febrile neutropenia (grade 4, 17%)
Thrombocytopenia (grade 4, 17%)
Other AEs:
Neutropenia (grade 3, 67%)
Leukopenia (grade 3, 50%)
Thrombocytopenia (grade 3, 67%)
Anemia (grade 3, 17%)
Febrile neutropenia (grade 3, 50%)
Lymphopenia (grade 3, 33%)
Pneumonia (grade 3, 33%)
Sources:
4 mg 1 times / day single, oral
Highest studied dose
Dose: 4 mg, 1 times / day
Route: oral
Route: single
Dose: 4 mg, 1 times / day
Sources: Page: 022334s000_MedR_P2.pdf - p.19
healthy
n = 4
Health Status: healthy
Population Size: 4
Sources: Page: 022334s000_MedR_P2.pdf - p.19
50 mg 1 times / day single, oral
Highest studied dose
Dose: 50 mg, 1 times / day
Route: oral
Route: single
Dose: 50 mg, 1 times / day
Sources: Page: 022334s000_MedR_P2.pdf - p.19
healthy
n = 61
Health Status: healthy
Population Size: 61
Sources: Page: 022334s000_MedR_P2.pdf - p.19
AEs

AEs

AESignificanceDosePopulation
AST increased grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Anorexia grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Dehydration grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Fatigue grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Hyperbilirubinemia grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Hypoalbuminemia grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Phosphatase alkaline increased grade 3, 1.4%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Mucositis grade 3, 1.4%
DLT
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Dyspnea grade 3, 2.9%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Hypersensitivity grade 3, 2.9%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Thrombocytopenia grade 3, 2.9%
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Rash grade 3, 2.9%
DLT
70 mg 1 times / week multiple, oral
MTD|Highest studied dose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Co-administed with::
cetuximab(250 mg/m2 IV: 4 weeks)
Sources: Page: 022334s000_MedR_P2.pdf - p.19
unhealthy, mean age 60 years
n = 16
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 16
Sources: Page: 022334s000_MedR_P2.pdf - p.19
Hypersensitivity grade 3, 16.7%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 6
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 6
Sources:
Anemia grade 3, 2%
50 mg 1 times / week multiple, oral
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 7
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 7
Sources:
Hyperbilirubinemia grade 3, 2%
50 mg 1 times / week multiple, oral
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 7
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 7
Sources:
Hypersensitivity grade 3, 2%
50 mg 1 times / week multiple, oral
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 7
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 7
Sources:
Hypokalemia grade 3, 2%
DLT
50 mg 1 times / week multiple, oral
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Co-administed with::
(250 mg/m2 IV: 4 weeks)
Sources:
unhealthy, mean age 60 years
n = 7
Health Status: unhealthy
Condition: advanced cancer
Age Group: mean age 60 years
Sex: M+F
Population Size: 7
Sources:
Anemia grade 3, 25%
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Neutropenia grade 3, 25%
DLT
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Leukopenia grade 3, 50%
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Neutropenia grade 3, 50%
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Febrile neutropenia grade 4, 25%
DLT
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 51 years
n = 4
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 51 years
Sex: M+F
Population Size: 4
Sources:
Interstitial pneumonitis grade 2, 14.3%
DLT, Disc. AE
20 mg 1 times / week multiple, oral
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 7
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 7
Sources:
Asthenia grade 3, 10%
35 mg 1 times / week multiple, oral (mean)
Dose: 35 mg, 1 times / week
Route: oral
Route: multiple
Dose: 35 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 10
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 10
Sources:
Oesophagitis grade 3, 10%
35 mg 1 times / week multiple, oral (mean)
Dose: 35 mg, 1 times / week
Route: oral
Route: multiple
Dose: 35 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 10
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 10
Sources:
Dermatitis grade 3, 20%
35 mg 1 times / week multiple, oral (mean)
Dose: 35 mg, 1 times / week
Route: oral
Route: multiple
Dose: 35 mg, 1 times / week
Sources:
unhealthy, median age 55.5 years
n = 10
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 55.5 years
Sex: M+F
Population Size: 10
Sources:
Anemia grade 3, 20%
20 mg 1 times / week multiple, oral
Recommended
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 5
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 5
Sources:
Leukopenia grade 3, 20%
20 mg 1 times / week multiple, oral
Recommended
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 5
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 5
Sources:
Hypokalemia grade 3, 40%
20 mg 1 times / week multiple, oral
Recommended
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 5
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 5
Sources:
Neutropenia grade 3, 80%
20 mg 1 times / week multiple, oral
Recommended
Dose: 20 mg, 1 times / week
Route: oral
Route: multiple
Dose: 20 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 5
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 5
Sources:
Febrile neutropenia grade 3, 15%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Leukopenia grade 3, 15%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Neutropenia grade 3, 15%
DLT
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Anemia grade 3, 23%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Hypokalemia grade 3, 23%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Thrombocytopenia grade 3, 23%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Neutropenia grade 3, 62%
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Febrile neutropenia grade 4, 7%
DLT
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Neutropenia grade 4, 7%
DLT
30 mg 1 times / week multiple, oral
Dose: 30 mg, 1 times / week
Route: oral
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 56 years
n = 13
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 56 years
Sex: M+F
Population Size: 13
Sources:
Pleural effusion 0.4%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Renal failure 0.4%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Abdominal pain 0.7%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Anorexia 0.7%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Arthralgia 0.7%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Edema peripheral 0.7%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pruritus 0.7%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Blood creatinine increased 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Constipation 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Dehydration 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Fatigue 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Fatigue 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Interstitial lung disease 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Nausea 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Vomiting 1.1%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Lung disorder 1.5%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pyrexia 1.5%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Rash 1.5%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Anemia 1.9%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Diarrhea 1.9%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Dyspnea 1.9%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Asthenia 2.2%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pneumonia 2.2%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Thrombocytopenia 2.2%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pneumonitis 2.6%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Dyspnea 3%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Mucosal inflammation 3%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pneumonitis 3.3%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Stomatitis 4.5%
Disc. AE
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
ALT increased grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Anorexia grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Blood creatinine increased grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Calcium increased grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Deep vein thrombosis grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Dry skin grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hepatic failure grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hyperlipidemia grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Interstitial lung disease grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Palmar-plantar erythrodysaesthesia syndrome grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Platelet count decreased grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pruritus grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pulmonary alveolar hemorrhage grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Sodium decreased grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Sodium increased grade 3, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
AST increased grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Alkaline phosphatase increased grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Bilirubin increased grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Blood glucose increased grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Blood triglycerides increased grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Erythema grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hypertriglyceridemia grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Lung infiltration grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Rash grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Renal failure grade 3, 0.7%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Diabetes mellitus grade 3, 1.1%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Mucosal inflammation grade 3, 1.1%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Thrombocytopenia grade 3, 1.1%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Asthenia grade 3, 1.5%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Diarrhea grade 3, 1.5%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Dyspnea grade 3, 1.5%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Lymphopenia grade 3, 1.5%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hypercholesterolemia grade 3, 1.9%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hyperglycemia grade 3, 2.2%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Infection grade 3, 2.2%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pneumonitis grade 3, 2.6%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Fatigue grade 3, 3%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Stomatitis grade 3, 3.3%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Anemia grade 3, 4.5%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Phosphate decreased grade 3, 4.5%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hemoglobin decreased grade 3, 8.9%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Bilirubin increased grade 4, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Hemoglobin decreased grade 4, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Pancreatitis acute grade 4, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Renal failure acute grade 4, 0.4%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Infection grade 4, 1.1%
10 mg 1 times / day multiple, oral
Recommended
unhealthy, median age 61 years
n = 269
Interstitial pneumonitis grade 2, 16.7%
DLT, Disc. AE
2.5 mg 1 times / day multiple, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 6
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 6
Sources:
Dysphagia grade 3
5 mg 1 times / day multiple, oral
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 5
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 5
Sources:
Interstitial pneumonitis grade 3, 20%
DLT
5 mg 1 times / day multiple, oral
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 5
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 5
Sources:
Oesophagitis grade 3, 20%
DLT
5 mg 1 times / day multiple, oral
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 5
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 5
Sources:
Dyspnoea grade 4, 20%
DLT
5 mg 1 times / day multiple, oral
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Sources:
unhealthy, median age 62 years
n = 5
Health Status: unhealthy
Condition: non-small-cell lung cancer
Age Group: median age 62 years
Sex: M+F
Population Size: 5
Sources:
Anemia grade 3, 17%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Neutropenia grade 3, 17%
DLT
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Lymphopenia grade 3, 33%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Pneumonia grade 3, 33%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Febrile neutropenia grade 3, 50%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Leukopenia grade 3, 50%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Neutropenia grade 3, 67%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Thrombocytopenia grade 3, 67%
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Febrile neutropenia grade 4, 17%
DLT
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
Thrombocytopenia grade 4, 17%
DLT
5 mg 1 times / day multiple, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg, 1 times / day
Co-administed with::
cisplatin(75 mg/m2 IV; 1 per 3 weeks)
etoposide(100 mg/m2 IV; 2 per 3 weeks)
Sources:
unhealthy, median age 62.5 years
n = 6
Health Status: unhealthy
Condition: small-cell lung cancer
Age Group: median age 62.5 years
Sex: M+F
Population Size: 6
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes [IC50 9.42 uM]
yes [Ki 1.7 uM]
unlikely
Comment: In vitro everolimus inhibited CYP3A and 2D6, however, based on Ki values a significant effect on the metabolism of CYP3A or 2D6 is not expected.
Page: -
yes [Ki 2.3 uM]
unlikely
Comment: In vitro everolimus inhibited CYP3A and 2D6, however, based on Ki values a significant effect on the metabolism of CYP3A or 2D6 is not expected.
Page: -
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
yes
yes (co-administration study)
Comment: Based on the results from the drug-drug interaction studies with ketoconazole, erythromycin and verapamil no dose adjustments wil be provided in the label since the increases in everolimus exposures can not be adjusted by lowering the dose to 5 mg QD. For strong CYP3A4 inducers, a dose increase to 20 mg would compensate for the decrease in everolimus exposure. For strong CYP3A4 inhibitors because of the significant increase in exposure labeling instructions co-administration is not recom
Page: -
yes
yes (co-administration study)
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Reduced BCL2 and CCND1 mRNA expression in human cervical cancer HeLa cells treated with a combination of everolimus and paclitaxel.
2016
Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors.
2016 Mar 15
mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.
2016 Nov
Patents

Sample Use Guides

Advanced HR+ BC, advanced NET, advanced RCC, or renal angiomyolipoma with TSC: 10 mg once daily with or without food.
Route of Administration: Oral
Everolimus effectively inhibited cell growth at concentrations under 100 nM (IC(50)) in five triple-negative breast cancers cell lines and even in the 1-nM range in three of the five cell lines.
Name Type Language
EVEROLIMUS
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
EVEROLIMUS [MART.]
Common Name English
RAD-666
Code English
SDZ RAD
Common Name English
EVEROLIMUS [ORANGE BOOK]
Common Name English
ZORTRESS
Brand Name English
RAD001
Code English
EVEROLIMUS [USP-RS]
Common Name English
SDZ-RAD
Code English
EVEROLIMUS [INN]
Common Name English
CERTICAN
Brand Name English
AFINITOR
Brand Name English
EVEROLIMUS [EP MONOGRAPH]
Common Name English
EVEROLIMUS [USAN]
Common Name English
EVEROLIMUS [MI]
Common Name English
VOTUBIA
Brand Name English
RAD-001
Code English
EVEROLIMUS [JAN]
Common Name English
EVEROLIMUS [EMA EPAR]
Common Name English
RAD 666
Code English
40-O-(2-HYDROXYETHYL)-RAPAMYCIN
Common Name English
EVEROLIMUS [VANDF]
Common Name English
EVEROLIMUS [WHO-DD]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175625
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
WHO-ATC L04AA18
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
EU-Orphan Drug EU/3/07/488
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 315410
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
WHO-VATC QL04AA18
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 374012
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
EMA ASSESSMENT REPORTS VOTUBIA (AUTHORIZED: TUBEROUS SCLEROSIS)
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
NCI_THESAURUS C574
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
NCI_THESAURUS C2201
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
EMA ASSESSMENT REPORTS AFINITOR (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
WHO-ATC L01XE10
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 283609
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 254107
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
EMA ASSESSMENT REPORTS AFINITOR (AUTHORIZED: PANCREATIC NEOPLASMS)
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 489715
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
NDF-RT N0000175076
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 340111
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
NCI_THESAURUS C1742
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
WHO-VATC QL01XE10
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
LIVERTOX 393
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
FDA ORPHAN DRUG 431214
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
Code System Code Type Description
FDA UNII
9HW64Q8G6G
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
HSDB
8255
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
MERCK INDEX
M5220
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1908360
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
NDF-RT
N0000182141
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
DRUG BANK
DB01590
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
INN
7863
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
CAS
159351-69-6
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
IUPHAR
5889
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
WIKIPEDIA
EVEROLIMUS
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
MESH
C107135
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
USP_CATALOG
1268976
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY USP-RS
EPA CompTox
159351-69-6
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
PUBCHEM
6442177
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
DRUG CENTRAL
1118
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
NDF-RT
N0000182137
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
EVMPD
SUB02065MIG
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
NDF-RT
N0000185503
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
RXCUI
141704
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C48387
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY
LACTMED
Everolimus
Created by admin on Fri Jun 25 21:06:46 UTC 2021 , Edited by admin on Fri Jun 25 21:06:46 UTC 2021
PRIMARY