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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22F2N6O2.H2O4S
Molecular Weight 526.5156
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAROTRECTINIB SULFATE

SMILES

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

InChI

InChIKey=PXHANKVTFWSDSG-QLOBERJESA-N
InChI=1S/C21H22F2N6O2.H2O4S/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;1-5(2,3)4/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31);(H2,1,2,3,4)/t14-,18+;/m0./s1

HIDE SMILES / InChI

Molecular Formula H2O4S
Molecular Weight 98.0796
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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

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

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1543104000000
Primary
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
788 ng/mL
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
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
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased...
Dose limiting toxicities:
Alanine aminotransferase increased (1 patient)
Aspartate aminotransferase increased (1 patient)
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
DLT: Dizziness...
Dose limiting toxicities:
Dizziness (1 patient)
Sources:
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:
unhealthy, adult
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
DLT: Dizziness...
Dose limiting toxicities:
Dizziness (1 patient)
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, 28 - 82 years
Health Status: unhealthy
Age Group: 28 - 82 years
Sex: M+F
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes (co-administration study)
Comment: larotrectinib increased midazolam both AUC and Cmax by 1.7-fold
Page: 94
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
yes [Km >300 uM]
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
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

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

Oral capsule of LOXO-101 (ARRY-470 (FREE BASE)) - 100mg BID
Route of Administration: Oral
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 05:22:06 UTC 2021
Edited
by admin
on Sat Jun 26 05:22:06 UTC 2021
Record UNII
RDF76R62ID
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LAROTRECTINIB SULFATE
USAN  
USAN  
Official Name English
VITRAKVI
Brand Name English
LAROTRECTINIB SULFATE [USAN]
Common Name English
1-PYRROLIDINECARBOXAMIDE, N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)-1-PYRROLIDINYL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXY-, (3S)-, SULFATE (1:1)
Systematic Name English
LAROTRECTINIB SULFATE [WHO-DD]
Common Name English
ARRY-470 SULFATE
Code English
(3S)-N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDIN-1-YL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE SULFATE (1:1)
Systematic Name English
LOXO-101 SULFATE
Code English
LAROTRECTINIB SULFATE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/15/1606
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
FDA ORPHAN DRUG 490115
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C156895
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
PRIMARY
DRUG BANK
DBSALT002820
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
PRIMARY
RXCUI
2104548
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
PRIMARY
FDA UNII
RDF76R62ID
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
PRIMARY
PUBCHEM
67330085
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
PRIMARY
CAS
1223405-08-0
Created by admin on Sat Jun 26 05:22:06 UTC 2021 , Edited by admin on Sat Jun 26 05:22:06 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY