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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H19FN6O2
Molecular Weight 406.413
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LORLATINIB

SMILES

C[C@H]1OC2=CC(=CN=C2N)C3=C(C#N)N(C)N=C3CN(C)C(=O)C4=CC=C(F)C=C14

InChI

InChIKey=IIXWYSCJSQVBQM-LLVKDONJSA-N
InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1

HIDE SMILES / InChI
Molecular Formula C21H19FN6O2
Molecular Weight 406.413
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800039198 | http://meetinglibrary.asco.org/content/143329-156

Lorlatinib is an investigational medicine that inhibits the anaplastic lymphoma kinase (ALK) and ROS1 proto-oncogene. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors. Lorlatinib has in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on a) the prior use of crizotinib and at least one other ALK inhibitor for metastatic disease, or b) the prior use of alectinib as the first ALK inhibitor therapy for metastatic disease, or c) the prior use of certinib as the first ALK inhibitor therapy for metastatic disease.

CNS Activity

Originator

Pfizer
420
Curator's Comment: # Pfizer

Approval Year

2018
436
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.07 nM [IC50]
Inhibitor
8297
 0.02 nM [IC50]
Inhibitor
8297
 2.7 nM [IC50]
Inhibitor
8297
 3.3 nM [IC50]
Inhibitor
8297
 6.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Approved
8429
Lorbrena

Approved Use

LORBRENA is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or alectinib as the first ALK inhibitor therapy for metastatic disease; or ceritinib as the first ALK inhibitor therapy for metastatic disease .

Launch Date

2018
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
577 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LORLATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5650 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LORLATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
24 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LORLATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
34%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LORLATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
unhealthy, 51 years
n = 3
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
Disc. AE: Cognitive disorder, Aphasia...
AEs leading to
discontinuation/dose reduction:
Cognitive disorder (2 patients)
Aphasia (2 patients)
Irritability (2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Disc. AE: Respiratory failure, Dyspnea...
AEs leading to
discontinuation/dose reduction:
Respiratory failure (1.4%)
Dyspnea (0.7%)
Myocardial infarction (0.7%)
Cognitive disorder NEC (0.7%)
Mood disorder (0.7%)
Edema (7%)
Hypertriglyceridemia (6%)
Peripheral neuropathy (5%)
Cognitive disorder NEC (4.4%)
Lipase increased (3.7%)
Hypercholesterolemia (3.4%)
Mood disorder (3.1%)
Dyspnea (2.7%)
Pneumonia (2.7%)
Hypertension (2%)
Edema (6%)
Peripheral neuropathy (4.7%)
Cognitive disorder NEC (4.1%)
Mood disorder (3.1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Disc. AE: Acute leukemia, Brain compression...
AEs leading to
discontinuation/dose reduction:
Acute leukemia (0.3%)
Brain compression (0.3%)
Embolism (0.3%)
Hallucinations (0.3%)
Headache (0.3%)
Hydrocephalus (0.3%)
Hypoxia (0.3%)
Leukocytosis (0.3%)
Loss of consciousness (0.3%)
Lung infection (0.3%)
Mental status changes (0.3%)
Parkinsonian gait (0.3%)
Peripheral swelling (0.3%)
Thrombocytopenia (0.3%)
Tinnitus (0.3%)
Vomiting (0.3%)
Hypertriglyceridemia (1.7%)
Arthralgia (1%)
Dizziness (1%)
Hallucinations (1%)
Weight increased (1%)
Blood amylase increased (1.7%)
Diarrhea (1.7%)
Fatigue (1.7%)
Asthenia (1.7%)
Dizziness (1.4%)
Fall (1.4%)
Hyperglycemia (1.4%)
Pyrexia (1.4%)
ALT increased (1%)
Anemia (1%)
Arthralgia (1%)
Atrial fibrillation (1%)
Back pain (1%)
Ejection fraction decreased (1%)
Mental status changes (1%)
Pericardial effusion (1%)
Pleural effusion (1%)
Acute respiratory failure (1%)
Respiratory failure (1%)
Vomiting (1%)
Weight increased (1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
AEs

AEs

AESignificanceDosePopulation
Aphasia 2 patients
Disc. AE
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
unhealthy, 51 years
n = 3
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
Cognitive disorder 2 patients
Disc. AE
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
unhealthy, 51 years
n = 3
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
Irritability 2 patients
Disc. AE
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
unhealthy, 51 years
n = 3
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/29074098
Cognitive disorder NEC 0.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Dyspnea 0.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Mood disorder 0.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Myocardial infarction 0.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Respiratory failure 1.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Hypertension 2%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Dyspnea 2.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Pneumonia 2.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Mood disorder 3.1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Mood disorder 3.1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Hypercholesterolemia 3.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Lipase increased 3.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Cognitive disorder NEC 4.1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Cognitive disorder NEC 4.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Peripheral neuropathy 4.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Peripheral neuropathy 5%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Edema 6%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Hypertriglyceridemia 6%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Edema 7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf
Acute leukemia 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Brain compression 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Embolism 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Hallucinations 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Headache 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Hydrocephalus 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Hypoxia 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Leukocytosis 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Loss of consciousness 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Lung infection 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Mental status changes 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Parkinsonian gait 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Peripheral swelling 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Thrombocytopenia 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Tinnitus 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Vomiting 0.3%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
ALT increased 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Acute respiratory failure 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Anemia 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Arthralgia 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Arthralgia 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Atrial fibrillation 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Back pain 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Dizziness 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Ejection fraction decreased 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Hallucinations 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Mental status changes 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Pericardial effusion 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Pleural effusion 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Respiratory failure 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Vomiting 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Weight increased 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Weight increased 1%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Dizziness 1.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Fall 1.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Hyperglycemia 1.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Pyrexia 1.4%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Asthenia 1.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Blood amylase increased 1.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Diarrhea 1.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Fatigue 1.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Hypertriglyceridemia 1.7%
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
unhealthy, 53 years (range: 19 - 85 years)
n = 295
Health Status: unhealthy
Condition: non-small cell lung cancer (NSCLC)
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Population Size: 295
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf
Page: p. 164
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
781

inhibitor
1587

substrate
1737
inhibitor
1767
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
BCRP
699

CYP1A2
1524

CYP2B6
810

CYP2C19
1478

CYP2C8
911

MATE1
306

MATE2
263

OAT1
599

OAT3
642

OATP1B1
788

OATP1B3
706

OCT1
512

OCT2
647

P-gp
1461

UGT1A1
204

UGT1A4
77

UGT1A6
108

UGT1A9
116

UGT2B7
146

Nav1.5
97
CYP2C19
991

CYP2C8
693

CYP3A5
395

UGT1A3
422

UGT1A4
347
CYP2B6
547
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
MATE2
263
 no
OAT1
603
 no
OATP1B1
803
 no
OATP1B3
715
 no
OCT2
648
 no
UGT1A1
254
 no
UGT1A4
80
 no
UGT1A6
141
 no
UGT1A9
121
 no
UGT2B7
157
 no
PXR
46
 yes [EC50 2.85 uM]
yes (co-administration study)
Comment: rifampin reduced mean lorlatinib AUC by 85% and Cmax by 76%
Page: 85.0
BCRP
773
 yes
CYP2B6
1001
 yes
CYP3A4
1925
 yes
MATE1
308
 yes
OAT3
644
 yes
OCT1
543
 yes
P-gp
1650
 yes
CYP3A4
1925
 yes
yes (co-administration study)
Comment: lorlatinib reduced midazolam AUC by 64% and Cmax by 50%
Page: 14.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
991
 minor
CYP2C8
693
 minor
CYP3A5
395
 minor
UGT1A3
422
 minor
UGT1A4
347
 yes
CYP3A4
1737
 yes
yes (co-administration study)
Comment: rifampin reduced mean lorlatinib AUC by 85% and Cmax by 76%; Itraconazole increased lorlatinib AUC by 42% and Cmax by 24%
Page: 13, 14
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Nav1.5
100
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:143117
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:143117
ChemicalBook
CB02716543
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02716543
MolPort
MolPort-035-789-724
https://www.molport.com/shop/molecule-link/MolPort-035-789-724
ZINC
ZINC000098208524
http://zinc15.docking.org/substances/ZINC000098208524
PubMed

PubMed

TitleDatePubMed
Tackling ALK in non-small cell lung cancer: the role of novel inhibitors.
2016 Jun
The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.
2016 Sep 1
Patents

Patents

WO2015050989 A3
2
WO2016090034 A2
2

Sample Use Guides

In Vivo Use Guide
The recommended dosage is 100 mg orally once daily.
Route of Administration: Oral
In Vitro Use Guide
Mutant ALKG1128A, ALKF1174L, ALKR1192P, ALKF1245C and ALKR1275Q responded to PF-06463922 with IC50 values similar to that of wild-type, two mutants – ALKI1171N and ALKY1278S – were more resistant, with 4- and 2.8-fold (3.21 nM and 2.27 nM) respectively of the IC50 of wild-type ALK kinase.
Substance Class Chemical
Created
by admin
on Sat Dec 16 02:12:10 GMT 2023
Edited
by admin
on Sat Dec 16 02:12:10 GMT 2023
Record UNII
OSP71S83EU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LORLATINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
LORBRENA
Brand Name English
PF-06463922
Code English
lorlatinib [INN]
Common Name English
LORLATINIB [JAN]
Common Name English
(10R)-7-AMINO-12-FLUORO-2,10,16-TRIMETHYL-15-OXO-10,15,16,17-TETRAHYDRO-2H-4,8- METHENOPYRAZOLO(4,3-H)(2,5,11)BENZOXADIAZACYCLOTETRADECINE-3-CARBONITRILE
Systematic Name English
LORLATINIB [USAN]
Common Name English
2H-4,8-METHENOPYRAZOLO(4,3-H)(2,5,11)BENZOXADIAZACYCLOTETRADECINE-3-CARBONITRILE, 7-AMINO-12-FLUORO-10,15,16,17-TETRAHYDRO-2,10,16-TRIMETHYL-15-OXO-, (10R)-
Systematic Name English
Lorlatinib [WHO-DD]
Common Name English
LORLATINIB [MI]
Common Name English
LORLATINIB [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C141136
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
FDA ORPHAN DRUG 481015
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
WHO-ATC L01XE44
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
Code System Code Type Description
CAS
1454846-35-5
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
SMS_ID
100000166974
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
EPA CompTox
DTXSID201027944
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
NCI_THESAURUS
C113655
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
DRUG BANK
DB12130
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
INN
10278
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
DRUG CENTRAL
5302
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
PUBCHEM
71731823
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
USAN
CD-57
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
MERCK INDEX
m12113
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
LACTMED
Lorlatinib
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
RXCUI
2103164
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
DAILYMED
OSP71S83EU
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
ChEMBL
CHEMBL3286830
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
FDA UNII
OSP71S83EU
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
EVMPD
SUB181272
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
CHEBI
143117
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
WIKIPEDIA
Lorlatinib
Created by admin on Sat Dec 16 02:12:10 GMT 2023 , Edited by admin on Sat Dec 16 02:12:10 GMT 2023
PRIMARY
Related Record Type Details
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
MINOR
MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1
TRANSPORTER -> INHIBITOR
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
OAT-3
TRANSPORTER -> INHIBITOR
ANAPLASTIC LYMPHOMA KINASE 1151TINS
TARGET -> INHIBITOR
Ki
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
ANAPLASTIC LYMPHOMA KINASE
TARGET -> INHIBITOR
INHIBITOR
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
In vitro, protein binding of lorlatinib to human plasma proteins, including serum albumin and α1-acid glycoprotein, was 66% at a concentration of 2.4 μM.
BINDING
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INDUCER
Structure of LORLATINIB ACETATE
SALT/SOLVATE -> PARENT
PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ROS
TARGET -> INHIBITOR
IC50
ANAPLASTIC LYMPHOMA KINASE F1174L
TARGET -> INHIBITOR
Ki
ANAPLASTIC LYMPHOMA KINASE L1152R
TARGET -> INHIBITOR
Ki
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
OCT-1
TRANSPORTER -> INHIBITOR
POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 2
OFF TARGET->NON-INHIBITOR
did not predict QTc prolongation, by inhibition of the hERG channel at clinically relevant concentrations
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
MINOR
OAT-1
TRANSPORTER -> INHIBITOR
SODIUM CHANNEL PROTEIN TYPE 5 SUBUNIT ALPHA
OFF TARGET->NON-INHIBITOR
failed to inhibit L-type calcium channel, or Nav1.5 sodium current at clinically relevant concentrations.
CYTOCHROME P450 2B6
METABOLIC ENZYME -> INDUCER
ACTIVATOR
ANAPLASTIC LYMPHOMA KINASE C1156Y
TARGET -> INHIBITOR
Ki
CYTOCHROME P450 3A5
METABOLIC ENZYME -> SUBSTRATE
MINOR
ANAPLASTIC LYMPHOMA KINASE S1206Y
TARGET -> INHIBITOR
Ki
ANAPLASTIC LYMPHOMA KINASE G1269A
TARGET -> INHIBITOR
Ki
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
MINOR
Structure of LORLATINIB
EXCRETED UNCHANGED
Following a single oral 100 mg dose of radiolabeled lorlatinib, 48% of the radioactivity was recovered in urine (< 1% as unchanged) and 41% in feces (about 9% as unchanged).
FECAL; URINE
ANAPLASTIC LYMPHOMA KINASE L1196M
TARGET -> INHIBITOR
Ki
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
TIME-DEPENDENT INHIBITION
Ki
ANAPLASTIC LYMPHOMA KINASE G1202R
TARGET -> INHIBITOR
Ki
Related Record Type Details
Structure of PF- 06895751
METABOLITE INACTIVE -> PARENT
Related Record Type Details
Structure of LORLATINIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Cmax PHARMACOKINETIC ROUTE OF ADMINSTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC SINGLE DOSE

ORAL

Blood-to-plasma ratio PHARMACOKINETIC
Tmax PHARMACOKINETIC SINGLE DOSE

ORAL

Biological Half-life PHARMACOKINETIC SINGLE DOSE

INTRAVENOUS

Volume of Distribution PHARMACOKINETIC SINGLE DOSE

INTRAVENOUS

NIH
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