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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22F2N6O2
Molecular Weight 428.436
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAROTRECTINIB

SMILES

C1C[C@]([H])(c2cc(ccc2F)F)N(C1)c3ccn4c(c(cn4)N=C(N5CC[C@@]([H])(C5)O)O)n3

InChI

InChIKey=NYNZQNWKBKUAII-KBXCAEBGSA-N
InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1

HIDE SMILES / InChI
Molecular Formula C21H22F2N6O2
Molecular Weight 428.436
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Larotrectinib (previously known as ARRY-470 and LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Larotrectinib is in phase II clinical trials for the treatment patients with solid tumors, non-Hodgkin lymphoma and for the pediatric patients with advanced solid or primary CNS tumors.

CNS Activity

CNS Non-penetrant
1062
Curator's Comment:: Known to be CNS non-penetrant in mouse. Human data not available

Originator

Approval Year

2018
397
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7728
Inhibitor
7728
 20.0 nM [IC50]
Inhibitor
7728
 20.0 nM [IC50]
Inhibitor
7728
 20.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8043
VITRAKVI

Approved Use

Vitrakvi is specifically indicated for the treatment of adult and pediatric patients with solid tumors that: • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, • are metastatic or where surgical resection is likely to result in severe morbidity, and • have no satisfactory alternative treatments or that have progressed following treatment.

Launch Date

1.54310397E12
Primary
Phase II
1101
Unknown

Approved Use

Unknown
Primary
Phase II
1101
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
788 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LAROTRECTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4351 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LAROTRECTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.9 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LAROTRECTINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Disc. AE: Brain edema, Intestinal perforation...
Other AEs: Fatigue, Nausea...
AEs leading to
discontinuation/dose reduction:
Brain edema (1 - 2)
Intestinal perforation (1 - 2)
Pericardial effusion (1 - 2)
Pleural effusion (1 - 2)
Small intestinal obstruction (1 - 2)
Dehydration (1 - 2)
Fatigue (1 - 2)
ALT increased (1 - 2)
AST increased (1 - 2)
Enterocutaneous fistula (1 - 2)
Amylase increased (1 - 2)
Lipase increased (1 - 2)
Muscular weakness (1 - 2)
Abdominal pain (1 - 2)
Asthenia (1 - 2)
Decreased appetite (1 - 2)
Dyspnea (1 - 2)
Hyponatremia (1 - 2)
Jaundice (1 - 2)
Syncope (1 - 2)
Vomiting (1 - 2)
Nausea (1 - 2)
Acute myeloid leukemia (1 - 2)
Other AEs:
Fatigue (>20)
Nausea (>20)
Dizziness (>20)
Vomiting (>20)
Anemia (>20)
AST increased (>20)
Cough (>20)
ALT increased (>20)
Constipation (>20)
Diarrhea (>20)
ALT increased (6%)
AST increased (6%)
Dizziness (3%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Other AEs: Fatigue, Pyrexia...
Other AEs:
Fatigue (all grades, 37%)
Pyrexia (all grades, 18%)
Edema peripheral (all grades, 15%)
Nausea (all grades, 29%)
Vomiting (all grades, 26%)
Constipation (all grades, 23%)
Diarrhea (all grades, 22%)
Abdominal pain (all grades, 13%)
Dizziness (all grades, 28%)
Headache (all grades, 14%)
Cough (all grades, 26%)
Dyspnea (all grades, 18%)
Nasal congestion (all grades, 10%)
Fatigue (grade 3-4, 3%)
Pyrexia (grade 3-4, 1%)
Nausea (grade 3-4, 1%)
Vomiting (grade 3-4, 1%)
Constipation (grade 3-4, 1%)
Diarrhea (grade 3-4, 2%)
Abdominal pain (grade 3-4, 2%)
Dizziness (grade 3-4, 1%)
Dyspnea (grade 3-4, 2%)
Weight increased (all grades, 15%)
Arthralgia (all grades, 14%)
Myalgia (all grades, 14%)
Muscular weakness (all grades, 13%)
Back pain (all grades, 12%)
Pain in extremity (all grades, 12%)
Decreased appetite (all grades, 13%)
Decreased appetite (all grades, 11%)
Weight increased (grade 3-4, 4%)
Arthralgia (grade 3-4, 1%)
Myalgia (grade 3-4, 1%)
Back pain (grade 3-4, 1%)
Pain in extremity (grade 3-4, 1%)
Decreased appetite (grade 3-4, 2%)
Decreased appetite (grade 3-4, 2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Other AEs: ALT increased, AST increased...
Other AEs:
ALT increased (all grades, 45%)
AST increased (all grades, 45%)
Hypoalbuminemia (all grades, 35%)
Alkaline phosphatase increased (all grades, 30%)
Anemia (all grades, 42%)
Neutropenia (all grades, 23%)
ALT increased (grade 3-4, 3%)
AST increased (grade 3-4, 3%)
Hypoalbuminemia (grade 3-4, 2%)
Alkaline phosphatase increased (grade 3-4, 3%)
Anemia (grade 3-4, 10%)
Neutropenia (grade 3-4, 7%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
150 mg 2 times / day steady, oral
Higher than recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased...
Dose limiting toxicities:
Alanine aminotransferase increased (1 patient)
Aspartate aminotransferase increased (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
200 mg 2 times / day steady, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
DLT: Dizziness...
Dose limiting toxicities:
Dizziness (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
200 mg 2 times / day steady, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf
Page: 91
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumor
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf
Page: 91
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf
Page: 91
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
DLT: Dizziness...
Dose limiting toxicities:
Dizziness (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
AEs

AEs

AESignificanceDosePopulation
ALT increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
AST increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Abdominal pain 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Acute myeloid leukemia 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Amylase increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Asthenia 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Brain edema 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Decreased appetite 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Dehydration 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Dyspnea 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Enterocutaneous fistula 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Fatigue 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Hyponatremia 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Intestinal perforation 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Jaundice 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Lipase increased 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Muscular weakness 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Nausea 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Pericardial effusion 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Pleural effusion 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Small intestinal obstruction 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Syncope 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Vomiting 1 - 2
Disc. AE
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Dizziness 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
ALT increased 6%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
AST increased 6%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
ALT increased >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
AST increased >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Anemia >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Constipation >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Cough >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Diarrhea >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Dizziness >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Fatigue >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Nausea >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Vomiting >20
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: 6.1
Nasal congestion all grades, 10%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Decreased appetite all grades, 11%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Back pain all grades, 12%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Pain in extremity all grades, 12%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Abdominal pain all grades, 13%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Decreased appetite all grades, 13%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Muscular weakness all grades, 13%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Arthralgia all grades, 14%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Headache all grades, 14%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Myalgia all grades, 14%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Edema peripheral all grades, 15%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Weight increased all grades, 15%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Dyspnea all grades, 18%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Pyrexia all grades, 18%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Diarrhea all grades, 22%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Constipation all grades, 23%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Cough all grades, 26%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Vomiting all grades, 26%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Dizziness all grades, 28%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Nausea all grades, 29%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Fatigue all grades, 37%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Arthralgia grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Back pain grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Constipation grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Dizziness grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Myalgia grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Nausea grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Pain in extremity grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Pyrexia grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Vomiting grade 3-4, 1%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Abdominal pain grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Decreased appetite grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Decreased appetite grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Diarrhea grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Dyspnea grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Fatigue grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Weight increased grade 3-4, 4%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 2
Neutropenia all grades, 23%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Alkaline phosphatase increased all grades, 30%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Hypoalbuminemia all grades, 35%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Anemia all grades, 42%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
ALT increased all grades, 45%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
AST increased all grades, 45%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Anemia grade 3-4, 10%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Hypoalbuminemia grade 3-4, 2%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
ALT increased grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
AST increased grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Alkaline phosphatase increased grade 3-4, 3%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Neutropenia grade 3-4, 7%
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
unhealthy, 28 - 82 years
n = 176
Health Status: unhealthy
Condition: solid tumor
Age Group: 28 - 82 years
Sex: M+F
Population Size: 176
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf
Page: Table 3
Alanine aminotransferase increased 1 patient
DLT
150 mg 2 times / day steady, oral
Higher than recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
Aspartate aminotransferase increased 1 patient
DLT
150 mg 2 times / day steady, oral
Higher than recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
Dizziness 1 patient
DLT
200 mg 2 times / day steady, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
Dizziness 1 patient
DLT
100 mg 2 times / day steady, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid tumours
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/30624546/
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
707

inhibitor
1467

substrate
1601
inhibitor
1604
inhibitor
1702
inhibitor
1475

OverviewOther

Other InhibitorOther SubstrateOther Inducer
BCRP
643

BSEP
376

CYP1A2
1383

CYP2B6
717

CYP2C19
1325

CYP2C8
818

MATE1
290

MATE2
251

OAT1
554

OAT3
588

OATP1B1
733

OATP1B3
657

OCT1
480

OCT2
594

P-gp
1330
BCRP
515

OAT1
294

OAT3
305

OATP1B1
370

OATP1B3
319

OCT1
302

OCT2
316

P-gp
1400
CYP1A2
637

CYP2B6
501
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BCRP
713
 no
BSEP
377
 no
CYP1A2
1532
 no
CYP1A2
1532
 no
CYP2B6
884
 no
CYP2B6
884
 no
CYP2C19
1392
 no
CYP2C8
865
 no
CYP2C9
1648
 no
CYP2D6
1738
 no
MATE1
292
 no
MATE2
251
 no
OAT1
558
 no
OAT3
590
 no
OATP1B1
748
 no
OATP1B3
666
 no
OCT1
495
 no
OCT2
595
 no
P-gp
1514
 no
CYP3A4
1772
 yes
CYP3A4
1772
 yes
yes (co-administration study)
Comment: larotrectinib increased midazolam both AUC and Cmax by 1.7-fold
Page: 94.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
OAT1
294
 no
OAT3
305
 no
OATP1B1
370
 no
OATP1B3
319
 no
OCT1
302
 no
OCT2
316
 no
BCRP
515
 yes [Km >300 uM]
P-gp
1400
 yes [Km >300 uM]
yes (co-administration study)
Comment: rifampin increased larotrectinib AUC by 1.7-fold and Cmax by 1.8-fold
Page: 93, 94, 106
CYP3A4
1601
 yes
yes (co-administration study)
Comment: coadministration with midazolam increased midazolam AUC and Cmax by 1.7-fold; itraconazole increased larotrectinib AUC by 4.3-fold and Cmax by 2.8-fold; rifampin decreased larotrectinib AUC by 81% and Cmax by 71%
Page: 95, 104, 105
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1507
Sourcing

Sourcing

Vendor/AggregatorIDURL
AA Blocks
AA00171P
https://www.aablocks.com/goods/Goods/detail?id=AA00171P
Aaron Chemicals
AR0017TH
http://www.aaronchem.com/1223403-58-4
AbMole Bioscience
M6151
http://www.abmole.com/products/loxo-101.html
Acorn PharmaTech
ACN-043424
http://www.acornpharmatech.com/
BioChemPartner
BCP16262
http://www.biochempartner.com/1223403-58-4-BCP16262
Chem Scene
CS-5722
http://www.chemscene.com/1223403-58-4.html
Chemspace
CSSB00025704742
https://chem-space.com/CSSB00025704742
DC Chemicals
DC22338
http://www.dcchemicals.com/product_show-DC22338.html
Excenen
EX-A1981
https://www.excenen.com/searchresultlist.php?id=1223403-58-4
Huateng Pharma
F99712
http://en.huatengsci.com/product/Larotrectinib.html
Lab Network
LN01343982
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343982
MedChem Express
HY-12866
https://www.medchemexpress.com/LOXO-101.html
Selleck Chemicals
S5860
http://www.selleckchem.com/products/larotrectinib.html
Smolecule
S002173
http://www.smolecule.com/products/s002173
Smolecule
S532504
http://www.smolecule.com/products/s532504
THE BioTek
bt-253135
https://www.thebiotek.com/product/inhibitors/bt-253135
THE BioTek
bt-272566
https://www.thebiotek.com/product/inhibitors/bt-272566
abcr GmbH
AB463081
http://www.abcr.com/shop/en/AB463081
eNovation Chemicals
D572361
https://www.enovationchem.com/ProductDetails.asp?ProductID=D572361
PubMed

PubMed

TitleDatePubMed
Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.
2013 Nov
An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101.
2015 Oct
Targeting NTRK fusion in non-small cell lung cancer: rationale and clinical evidence.
2017 Jun
Rapid Response to Larotrectinib (LOXO-101) in an Adult Chemotherapy-Naive Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion.
2018 Jun

Sample Use Guides

In Vivo Use Guide
Oral capsule of LOXO-101 (ARRY-470 (FREE BASE)) - 100mg BID
Route of Administration: Oral
In Vitro Use Guide
ARRY-470 is a selective kinase inhibitor with nanomolar activity against TRKA/B/C but no other significant kinase inhibition below 1000nM. Treatment of cells expressing MPRIP- or CD74-NTRK1 with ARRY-470, CEP-701 and, to a lesser extent, crizotinib, inhibited autophosphorylation of RIP-TRKA and CD74-TRKA. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:58:44 UTC 2021
Edited
by admin
on Sat Jun 26 06:58:44 UTC 2021
Record UNII
PF9462I9HX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LAROTRECTINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
BAY-2757556
Code English
LOXO-101
Code English
ARRY-470
Code English
LAROTRECTINIB [USAN]
Common Name English
LAROTRECTINIB [WHO-DD]
Common Name English
1-PYRROLIDINECARBOXAMIDE, N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)-1-PYRROLIDINYL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXY-, (3S)-
Systematic Name English
LAROTRECTINIB [INN]
Common Name English
(3S)-N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDIN- 1-YL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE- 1-CARBOXAMIDE
Systematic Name English
BAY2757556
Code English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
NCI_THESAURUS C1967
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
EU-Orphan Drug EU/3/18/2098
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
FDA ORPHAN DRUG 578317
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
Code System Code Type Description
DRUG BANK
DB14723
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
CAS
1223403-58-4
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
LOXO-101
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY MedKoo CAT NO: 206207CAS NO: 1223403-58-4Description: LOXO-101, also known as ARRY-470, is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. (Last updated: 6/9/2016).
DRUG CENTRAL
5305
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
NCI_THESAURUS
C115977
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
FDA UNII
PF9462I9HX
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545075
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
PUBCHEM
46188928
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
RXCUI
2105628
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
ARRY 470
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY Biological Activity: LOXO-101 is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models. The TRK family of neurotrophin receptors, TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. Translocations involving the TRK kinase domain, mutations involving the TRK ligand-binding site, amplifications of NTRK, TRK splice variants, and autocrine/paracrine signaling are described in diverse tumor types, and may contribute to tumorigenesis. LOXO-101 is currently being developed by Loxo Oncology, Inc.
INN
10360
Created by admin on Sat Jun 26 06:58:44 UTC 2021 , Edited by admin on Sat Jun 26 06:58:44 UTC 2021
PRIMARY
Related Record Type Details
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MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
In overexpressing BCRP and P-gp cell line, the estimate Km for both transporters is >300 ?M. Coadministration of larotrectinib with a single dose of a P-gp inhibitor (rifampin), increased the AUCinf of larotrectinib by 1.7-fold and the Cmax by 1.8-fold as compared to larotrectinib administered alone.
Structure of LAROTRECTINIB
EXCRETED UNCHANGED
Following oral administration of a single [14C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine
FECAL; URINE
HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR
TARGET -> INHIBITOR
Active against NTRK gene fusions. Competitive to ATP binding site.
COMPETITIVE INHIBITOR
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Structure of LAROTRECTINIB SULFATE
SALT/SOLVATE -> PARENT
NT-3 GROWTH FACTOR RECEPTOR
TARGET -> INHIBITOR
IC50
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
Coadministration of multiple doses of larotrectinib with a sensitive CYP3A4 substrate (midazolam) increased the AUCinf and Cmax of midazolam by 1.7-fold as compared to midazolam administered alone.
BDNF/NT-3 GROWTH FACTORS RECEPTOR
TARGET -> INHIBITOR
IC50
Related Record Type Details
Structure of LAROTRECTINIB
ACTIVE MOIETY
LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in preclinical models. LOXO-101 is an orally bioavailable, potent, ATP-competitive inhibitor of TRKA, TRKB, and TRKC. LOXO-101 has IC50 values in the low nanomolar range for inhibition of all three TRK family members in binding and cellular assays, with 100x selectivity over other kinases, and has shown acceptable pharmaceutical properties and safety in nonclinical models.
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL

DOSE

Volume of Distribution PHARMACOKINETIC DOSE

Tmax PHARMACOKINETIC BID

NIH
NCATS
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