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Details

Stereochemistry ACHIRAL
Molecular Formula C9H11ClN4O2
Molecular Weight 242.6625
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIPIRACIL

SMILES

C1CC(=N)N(C1)Cc2c(c(nc(n2)O)O)Cl

InChI

InChIKey=QQHMKNYGKVVGCZ-UHFFFAOYSA-N
InChI=1S/C9H11ClN4O2/c10-7-5(12-9(16)13-8(7)15)4-14-3-1-2-6(14)11/h11H,1-4H2,(H2,12,13,15,16)

HIDE SMILES / InChI

Molecular Formula C9H11ClN4O2
Molecular Weight 242.6625
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28979148 | https://www.ncbi.nlm.nih.gov/pubmed/27568360 | https://www.ncbi.nlm.nih.gov/pubmed/28242161 | https://www.drugbank.ca/drugs/DB09343

Tipiracil is a thymidine phosphorylase inhibitor, that used for the treatment of patients with metastatic colorectal cancer. Tipiracil is used in combination with trifluridine as Lonsurf. Trifluridine is incorporated into DNA via phosphorylation, ultimately inhibiting cell proliferation. Tipiracil increases systemic exposure of trifluridine when coadministered. Lonsurf has recently been approved for the treatment of adult patients with metastatic colorectal cancer (mCRC) who are refractory to or are not considered candidates for, current standard chemotherapy and biological therapy in the EU and USA and in unresectable advanced or recurrent CRC in Japan. The approved regimen of oral twice-daily Lonsurf significantly improved overall survival and progression-free survival and was associated with a significantly higher disease control rate than placebo when added to best supportive care in the multinational, pivotal phase III trial (RECOURSE) and a phase II Japanese trial. Trifluridine/tipiracil was associated with an acceptable tolerability profile, with adverse events generally being managed with dose reductions, temporary interruptions in treatment or administration of granulocyte-colony stimulating factor. The most common grade 3–4 adverse events (>10 %) were anemia, neutropenia, thrombocytopenia, and leukopenia.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
20.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LONSURF

Approved Use

LONSURF is indicated for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. (1)

Launch Date

1.44288003E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
41.8 ng/mL
40 mg/m² 1 times / day multiple, oral
dose: 40 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
44.1 ng/mL
30 mg/m² 1 times / day multiple, oral
dose: 30 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
50.2 ng/mL
50 mg/m² 1 times / day multiple, oral
dose: 50 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
70 ng/mL
70 mg/m² 1 times / day multiple, oral
dose: 70 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
99.6 ng/mL
60 mg/m² 1 times / day multiple, oral
dose: 60 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
161 ng × h/mL
40 mg/m² 1 times / day multiple, oral
dose: 40 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
234 ng × h/mL
30 mg/m² 1 times / day multiple, oral
dose: 30 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
300 ng × h/mL
50 mg/m² 1 times / day multiple, oral
dose: 50 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
317 ng × h/mL
70 mg/m² 1 times / day multiple, oral
dose: 70 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
447 ng × h/mL
60 mg/m² 1 times / day multiple, oral
dose: 60 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.82 h
40 mg/m² 1 times / day multiple, oral
dose: 40 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.89 h
30 mg/m² 1 times / day multiple, oral
dose: 30 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4.01 h
50 mg/m² 1 times / day multiple, oral
dose: 50 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.37 h
70 mg/m² 1 times / day multiple, oral
dose: 70 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.21 h
60 mg/m² 1 times / day multiple, oral
dose: 60 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered: TRIFLURIDINE
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.4 h
35 mg/m² 2 times / day steady-state, oral
dose: 35 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
92%
35 mg/m² 2 times / day steady-state, oral
dose: 35 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TIPIRACIL HYDROCHLORIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 50 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 6
Sources:
Other AEs: Granulocytopenia, Granulocytopenia...
Other AEs:
Granulocytopenia (grade 4, 50%)
Granulocytopenia (grade 3, 16.7%)
Sources:
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 3
Sources:
DLT: Anemia...
Other AEs: Granulocytopenia...
Dose limiting toxicities:
Anemia (grade 3, 50%)
Other AEs:
Granulocytopenia (grade 4, 100%)
Sources:
60 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 60 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 3
Sources:
DLT: Granulocytopenia...
Other AEs: Granulocytopenia...
Dose limiting toxicities:
Granulocytopenia (grade 4, 33.3%)
Other AEs:
Granulocytopenia (grade 3, 33.3%)
Sources:
180 mg/m2/day 1 times / day multiple, oral
Highest studied dose|MTD
Dose: 180 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
DLT: Granulocytopenia...
Other AEs: Fatigue, Nausea...
Dose limiting toxicities:
Granulocytopenia (grade 3-4, 66.7%)
Other AEs:
Fatigue (grade 1-2, 66.7%)
Nausea (grade 1-2, 50%)
Diarrhea (grade 1-2, 16.7%)
Sources:
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
DLT: Granulocytopenia...
Other AEs: Fatigue, Nausea...
Dose limiting toxicities:
Granulocytopenia (grade 3-4, 100%)
Other AEs:
Fatigue (grade 1-2, 66.7%)
Nausea (grade 1-2, 66.7%)
Anorexia (grade 1-2, 66.7%)
Diarrhea (grade 1-2, 33.3%)
Taste abnormality (grade 1-2, 33.3%)
Anemia (grade 1-2, 66.7%)
Anemia (grade 3-4, 33.3%)
Sources:
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Other AEs: Fatigue, Anorexia...
Other AEs:
Fatigue (grade 3-4, 16.7%)
Anorexia (grade 3-4, 16.7%)
Granulocytopenia (grade 3-4, 100%)
Sources:
120 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 120 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 9
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 9
Sources:
DLT: Granulocytopenia...
140 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 140 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 140 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Other AEs: Anemia...
150 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 150 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Other AEs: Granulocytopenia...
170 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 170 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 170 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
DLT: Nausea, Granulocytopenia...
Dose limiting toxicities:
Nausea (grade 3, 66.7%)
Granulocytopenia (grade 3-4, 66.7%)
Sources:
70 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 70 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 70 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
DLT: Granulocytopenia...
Dose limiting toxicities:
Granulocytopenia (grade 3-4, 50%)
Sources:
90 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 90 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 90 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Other AEs: Granulocytopenia, Anemia...
Other AEs:
Granulocytopenia (grade 3-4, 100%)
Anemia (grade 3-4, 33.3%)
Sources:
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.100
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.100
Other AEs: GGT increased...
Other AEs:
GGT increased (grade 3-4, 3%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.100
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.101
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.101
Other AEs: Diarrhea...
Other AEs:
Diarrhea (grade 3-4, 3%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.101
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.102
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.102
Other AEs: Leukopenia...
Other AEs:
Leukopenia (grade 3-4, 2.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.102
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.103
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.103
Other AEs: Platelet count decreased...
Other AEs:
Platelet count decreased (grade 3-4, 2.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.103
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.104
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.104
Other AEs: Dyspnea...
Other AEs:
Dyspnea (grade 3-4, 2.3%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.104
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.105
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.105
Other AEs: General physical health deterioration...
Other AEs:
General physical health deterioration (grade 3-4, 2.3%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.105
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.106
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.106
Other AEs: Abdominal pain...
Other AEs:
Abdominal pain (grade 3-4, 2.1%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.106
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.107
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.107
Other AEs: Hypokalemia...
Other AEs:
Hypokalemia (grade 3-4, 2.1%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.107
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.108
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.108
Other AEs: Thrombocytopenia...
Other AEs:
Thrombocytopenia (grade 3-4, 2.1%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.108
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.109
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.109
Other AEs: Vomiting...
Other AEs:
Vomiting (grade 3-4, 2.1%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.109
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.110
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.110
Other AEs: Pyrexia...
Other AEs:
Pyrexia (grade 3-5, 1.1%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.110
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.111
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.111
Other AEs: Constipation...
Other AEs:
Constipation (grade 3-5, 0.2%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.111
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.112
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.112
Other AEs: Cough...
Other AEs:
Cough (grade 3-5, 0.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.112
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.113
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.113
Other AEs: Edema peripheral...
Other AEs:
Edema peripheral (grade 3-5, 0.2%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.113
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.114
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.114
Other AEs: Stomatitis...
Other AEs:
Stomatitis (grade 3-5, 0.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.114
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.115
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.115
Other AEs: Back pain...
Other AEs:
Back pain (grade 3-5, 1.7%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.115
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.116
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.116
Other AEs: Weight decreased...
Other AEs:
Weight decreased (grade 3-5, 0.2%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.116
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.117
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.117
Other AEs: Abdominal pain upper...
Other AEs:
Abdominal pain upper (grade 3-5, 0.2%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.117
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.118
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.118
Other AEs: Ascites...
Other AEs:
Ascites (grade 3-5, 0.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.118
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.119
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.119
Other AEs: Mucosal inflammation...
Other AEs:
Mucosal inflammation (grade 3-5, 0.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.119
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.120
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.120
Other AEs: AST increased...
Other AEs:
AST increased (grade 3-5, 1.1%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.120
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.121
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.121
Other AEs: Hyponatremia...
Other AEs:
Hyponatremia (grade 3-5, 1.3%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.121
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.122
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.122
Other AEs: Back pain...
Other AEs:
Back pain (grade 3-5, 1.7%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.122
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.123
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.123
Other AEs: Tumor pain...
Other AEs:
Tumor pain (grade 3-5, 0.6%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.123
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.124
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.124
Other AEs: Hypertension...
Other AEs:
Hypertension (grade 3-5, 1.5%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.124
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.77
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.77
Disc. AE: Neutropenia...
AEs leading to
discontinuation/dose reduction:
Neutropenia (3.2%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.77
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.78
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.78
Disc. AE: Anemia...
AEs leading to
discontinuation/dose reduction:
Anemia (1.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.78
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.79
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.79
Disc. AE: Febrile neutropenia...
AEs leading to
discontinuation/dose reduction:
Febrile neutropenia (1.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.79
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.80
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.80
Disc. AE: Neutrophil count decreased...
AEs leading to
discontinuation/dose reduction:
Neutrophil count decreased (1.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.80
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.81
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.81
Disc. AE: Fatigue...
AEs leading to
discontinuation/dose reduction:
Fatigue (1.5%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.81
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.82
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.82
Disc. AE: Diarrhea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (1.3%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.82
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.83
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.83
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (0.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.83
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.84
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.84
Disc. AE: Decreased appetite...
AEs leading to
discontinuation/dose reduction:
Decreased appetite (0.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.84
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.85
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.85
Disc. AE: Vomiting...
AEs leading to
discontinuation/dose reduction:
Vomiting (0.8%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.85
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.86
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.86
Disc. AE: Asthenia...
AEs leading to
discontinuation/dose reduction:
Asthenia (0.6%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.86
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.87
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.87
Disc. AE: Mucosal inflammation...
AEs leading to
discontinuation/dose reduction:
Mucosal inflammation (0.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.87
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.88
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.88
Disc. AE: Blood alkaline phosphatase increased...
AEs leading to
discontinuation/dose reduction:
Blood alkaline phosphatase increased (0.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.88
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.89
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.89
Disc. AE: Platelet count decreased...
AEs leading to
discontinuation/dose reduction:
Platelet count decreased (0.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.89
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.90
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.90
Other AEs: Neutropenia...
Other AEs:
Neutropenia (grade 3-4, 23.8%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.90
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.91
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.91
Other AEs: Neutrophil count decreased...
Other AEs:
Neutrophil count decreased (grade 3-4, 18.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.91
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.92
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.92
Other AEs: Anemia...
Other AEs:
Anemia (grade 3-4, 15.6%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.92
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.93
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.93
Other AEs: White blood cell count decreased...
Other AEs:
White blood cell count decreased (grade 3-4, 10.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.93
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.94
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.94
Other AEs: Fatigue...
Other AEs:
Fatigue (grade 3-4, 3.9%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.94
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.95
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.95
Other AEs: Blood bilirubin increased...
Other AEs:
Blood bilirubin increased (grade 3-4, 3.8%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.95
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.96
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.96
Other AEs: Febrile neutropenia...
Other AEs:
Febrile neutropenia (grade 3-4, 3.8%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.96
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.97
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.97
Other AEs: Decreased appetite...
Other AEs:
Decreased appetite (grade 3-4, 3.6%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.97
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.98
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.98
Other AEs: Asthenia...
Other AEs:
Asthenia (grade 3-4, 3.4%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.98
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.99
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.99
Other AEs: Blood alkaline phosphatase increased...
Other AEs:
Blood alkaline phosphatase increased (grade 3-4, 3.2%)
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.99
AEs

AEs

AESignificanceDosePopulation
Granulocytopenia grade 3, 16.7%
50 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 50 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 6
Sources:
Granulocytopenia grade 4, 50%
50 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 50 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 6
Sources:
Anemia grade 3, 50%
DLT
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 4, 100%
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 3, 33.3%
60 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 60 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 4, 33.3%
DLT
60 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 60 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 54 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 54 years
Sex: M+F
Population Size: 3
Sources:
Diarrhea grade 1-2, 16.7%
180 mg/m2/day 1 times / day multiple, oral
Highest studied dose|MTD
Dose: 180 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Nausea grade 1-2, 50%
180 mg/m2/day 1 times / day multiple, oral
Highest studied dose|MTD
Dose: 180 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Fatigue grade 1-2, 66.7%
180 mg/m2/day 1 times / day multiple, oral
Highest studied dose|MTD
Dose: 180 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Granulocytopenia grade 3-4, 66.7%
DLT
180 mg/m2/day 1 times / day multiple, oral
Highest studied dose|MTD
Dose: 180 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Diarrhea grade 1-2, 33.3%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Taste abnormality grade 1-2, 33.3%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Anemia grade 1-2, 66.7%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Anorexia grade 1-2, 66.7%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Fatigue grade 1-2, 66.7%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Nausea grade 1-2, 66.7%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 3-4, 100%
DLT
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Anemia grade 3-4, 33.3%
110 mg/m2/day 1 times / day multiple, oral
MTD
Dose: 110 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 110 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 3-4, 100%
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Anorexia grade 3-4, 16.7%
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Fatigue grade 3-4, 16.7%
100 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 100 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Granulocytopenia grade 3-4, 33.3%
DLT
120 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 120 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 9
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 9
Sources:
Anemia grade 3-4, 33.3%
140 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 140 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 140 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 3-4, 33.3%
150 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 150 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Nausea grade 3, 66.7%
DLT
170 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 170 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 170 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 3-4, 66.7%
DLT
170 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 170 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 170 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Granulocytopenia grade 3-4, 50%
DLT
70 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 70 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 70 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 6
Sources:
Granulocytopenia grade 3-4, 100%
90 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 90 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 90 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
Anemia grade 3-4, 33.3%
90 mg/m2/day 1 times / day multiple, oral
Studied dose
Dose: 90 mg/m2/day, 1 times / day
Route: oral
Route: multiple
Dose: 90 mg/m2/day, 1 times / day
Sources:
unhealthy, median age 59 years
n = 3
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 59 years
Sex: M+F
Population Size: 3
Sources:
GGT increased grade 3-4, 3%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.100
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.100
Diarrhea grade 3-4, 3%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.101
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.101
Leukopenia grade 3-4, 2.4%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.102
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.102
Platelet count decreased grade 3-4, 2.4%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.103
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.103
Dyspnea grade 3-4, 2.3%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.104
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.104
General physical health deterioration grade 3-4, 2.3%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.105
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.105
Abdominal pain grade 3-4, 2.1%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.106
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.106
Hypokalemia grade 3-4, 2.1%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.107
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.107
Thrombocytopenia grade 3-4, 2.1%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.108
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.108
Vomiting grade 3-4, 2.1%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.109
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.109
Pyrexia grade 3-5, 1.1%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.110
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.110
Constipation grade 3-5, 0.2%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.111
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.111
Cough grade 3-5, 0.4%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.112
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.112
Edema peripheral grade 3-5, 0.2%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.113
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.113
Stomatitis grade 3-5, 0.4%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.114
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.114
Back pain grade 3-5, 1.7%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.115
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.115
Weight decreased grade 3-5, 0.2%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.116
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.116
Abdominal pain upper grade 3-5, 0.2%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.117
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.117
Ascites grade 3-5, 0.9%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.118
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.118
Mucosal inflammation grade 3-5, 0.4%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.119
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.119
AST increased grade 3-5, 1.1%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.120
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.120
Hyponatremia grade 3-5, 1.3%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.121
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.121
Back pain grade 3-5, 1.7%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.122
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.122
Tumor pain grade 3-5, 0.6%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.123
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.123
Hypertension grade 3-5, 1.5%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.124
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.124
Neutropenia 3.2%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.77
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.77
Anemia 1.9%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.78
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.78
Febrile neutropenia 1.9%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.79
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.79
Neutrophil count decreased 1.9%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.80
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.80
Fatigue 1.5%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.81
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.81
Diarrhea 1.3%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.82
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.82
Nausea 0.9%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.83
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.83
Decreased appetite 0.9%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.84
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.84
Vomiting 0.8%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.85
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.85
Asthenia 0.6%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.86
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.86
Mucosal inflammation 0.4%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.87
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.87
Blood alkaline phosphatase increased 0.4%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.88
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.88
Platelet count decreased 0.4%
Disc. AE
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.89
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.89
Neutropenia grade 3-4, 23.8%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.90
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.90
Neutrophil count decreased grade 3-4, 18.9%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.91
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.91
Anemia grade 3-4, 15.6%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.92
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.92
White blood cell count decreased grade 3-4, 10.9%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.93
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.93
Fatigue grade 3-4, 3.9%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.94
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.94
Blood bilirubin increased grade 3-4, 3.8%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.95
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.95
Febrile neutropenia grade 3-4, 3.8%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.96
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.96
Decreased appetite grade 3-4, 3.6%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.97
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.97
Asthenia grade 3-4, 3.4%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.98
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.98
Blood alkaline phosphatase increased grade 3-4, 3.2%
35 mg/m2 2 times / day multiple, oral
Recommended
Dose: 35 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 35 mg/m2, 2 times / day
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.99
unhealthy, median age 63 years
n = 533
Health Status: unhealthy
Condition: metastatic colorectal cancer
Age Group: median age 63 years
Sex: M+F
Population Size: 533
Sources: Page: nda/2015/207981Orig1s000MedR.pdf - p.99
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
no (co-administration study)
Comment: The population PK analysis suggested that concomitant administration of OCT2 inhibitors (n=24) had no effect on the PK parameters of trifluridine and tipiracil.
Page: 34.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer.
1998 Feb
Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening.
2003 Nov 3
Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model.
2004 Feb
Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor.
2004 Jan
Pharmacokinetic modeling of species-dependent enhanced bioavailability of trifluorothymidine by thymidine phosphorylase inhibitor.
2004 Jun
Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma.
2005 May 9
Thymidine phosphorylase from Escherichia coli: tight-binding inhibitors as enzyme active-site titrants.
2006 Feb
Therapeutic potential of the dual-targeted TAS-102 formulation in the treatment of gastrointestinal malignancies.
2007 Jun
[Influence of the thymidine phosphorylase (platelet-derived endothelial cell growth factor) on tumor angiogenesis. Catalytic activity of enzyme inhibitors].
2010
Repeated oral dosing of TAS-102 confers high trifluridine incorporation into DNA and sustained antitumor activity in mouse models.
2014 Dec
Patents

Patents

Sample Use Guides

In combination with trifluridine, 35 mg/m2 up to a maximum of 80 mg per dose (based on the trifluridine component) orally twice daily within one hour of completion of morning and evening meals on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.
Route of Administration: Oral
HCT 116, HCT-15, and HT-29 cells were seeded at appropriate concentrations in duplicates in six-well plates. Twenty-four hours after plating, the cells were treated with the trifluridine (FTD 2 mkM or 4 mkM), or IR alone, or the combination of both using the RX-650 CABINET X-Ray system (Faxitron Xray Corp., Wheeling, IL, USA) with 3.4 Gy/min for 0.6-2.4 min. Ten to 12 days after plating, cells were fixed with 20% glutaraldehyde, stained with 0.05% crystal violet, and the number of colonies containing at least 50 cells was determined. Trifluridine enhances the efficacy of IR.
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:47:06 UTC 2021
Edited
by admin
on Sat Jun 26 04:47:06 UTC 2021
Record UNII
NGO10K751P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIPIRACIL
DASH   INN   USAN   WHO-DD  
USAN   INN  
Official Name English
TPI (FREEBASE)
Code English
TIPIRACIL [USAN]
Common Name English
TIPIRACIL [INN]
Common Name English
TIPIRACIL [MI]
Common Name English
5-CHLORO-6-((2-IMINOPYRROLIDIN-1-YL)METHYL)PYRIMIDINE-2,4-(1H,3H)-DIONE
Common Name English
TIPIRACIL [WHO-DD]
Common Name English
MA-1
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 564116
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
NDF-RT N0000191870
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
Code System Code Type Description
FDA UNII
NGO10K751P
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
IUPHAR
8696
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
CAS
183204-74-2
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
ChEMBL
CHEMBL235668
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
NCI_THESAURUS
C152646
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
DRUG CENTRAL
4893
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
DRUG BANK
DB09343
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
NDF-RT
N0000191869
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY Thymidine Phosphorylase Inhibitors [MoA]
RXCUI
1670304
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY RxNorm
EVMPD
SUB174128
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
PUBCHEM
6323266
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
INN
9500
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
MERCK INDEX
M11862
Created by admin on Sat Jun 26 04:47:06 UTC 2021 , Edited by admin on Sat Jun 26 04:47:06 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
BINDER->LIGAND
The in vitro protein binding in human plasma is below 8% for tipiracil.
BINDING
EXCRETED UNCHANGED
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC SINGLE DOSE ADMINISTRATION

Biological Half-life PHARMACOKINETIC SINGLE DOSE ADMINISTRATION