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

Details

Stereochemistry ACHIRAL
Molecular Formula C30H32F6N4O
Molecular Weight 578.5917
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NETUPITANT

SMILES

CN(C(=O)C(C)(C)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C2=CN=C(C=C2C3=CC=CC=C3C)N4CCN(C)CC4

InChI

InChIKey=WAXQNWCZJDTGBU-UHFFFAOYSA-N
InChI=1S/C30H32F6N4O/c1-19-8-6-7-9-23(19)24-17-26(40-12-10-38(4)11-13-40)37-18-25(24)39(5)27(41)28(2,3)20-14-21(29(31,32)33)16-22(15-20)30(34,35)36/h6-9,14-18H,10-13H2,1-5H3

HIDE SMILES / InChI
Molecular Formula C30H32F6N4O
Molecular Weight 578.5917
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=16332435; http://www.ncbi.nlm.nih.gov/pubmed/?term=24631949

Fosnetupitant is a prodrug form of netupitant. Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK-1) receptors. Upon intravenous administration, fosnetupitant is converted by phosphatases to its active form. It competitively binds to and blocks the activity of NK-1 receptors in the central nervous system, by inhibiting binding of substance P (SP) to NK-1 receptors. This prevents delayed emesis, which is associated with SP secretion. AKYNZEO® is a combination of palonosetron, a serotonin-3 receptor antagonist, and netupitant (capsules for oral use) or fosnetupitant (injections for intravenous use). AKYNZEO® for injection is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

CNS Activity

CNS Non-penetrant
1040
Curator's Comment: Studies in rodents suggest that Netupitant behaves as a brain penetrant, orally active

Originator

Approval Year

2014
503
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2849
 0.95 nM [Ki]
Substance-P receptor
8
Target ID: P25103
Gene ID: 6869.0
Gene Symbol: TACR1
Target Organism: Homo sapiens (Human)
Antagonist
2849
 0.95 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
AKYNZEO

Approved Use

AKYNZEO for injection is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

Launch Date

2018
Preventing
Approved
8583
Akynzeo

Approved Use

To treat nausea and vomiting in patients undergoing cancer chemotherapy

Launch Date

2014
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
434 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NETUPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14401 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NETUPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
96 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NETUPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.5%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NETUPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Other AEs: Palpitations, Constipation...
Other AEs:
Palpitations (2%)
Constipation (4.1%)
Pain in extremity (2%)
Dizziness (2%)
Headache (10.2%)
Somnolence (2%)
Anxiety (2%)
Euphoric mood (2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Disc. AE: Neutropenia, Neoplasm progression...
AEs leading to
discontinuation/dose reduction:
Neutropenia (0.5%)
Neoplasm progression (0.5%)
Neoplasm malignant (0.4%)
Febrile neutropenia (0.2%)
Leukopenia (0.2%)
Thrombocytopenia (0.1%)
Peritonitis (0.1%)
Troponin increased (0.1%)
Stomatitis (0.2%)
ALT increased (0.2%)
Platelet count decreased (0.2%)
Angina pectoris (0.1%)
Myocardial ischaemia (0.1%)
Creatinine renal clearance decreased (0.1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Other AEs: Febrile neutropenia, Neutropenia...
Other AEs:
Febrile neutropenia (1.5%)
Neutropenia (1%)
Vomiting (0.6%)
Anaemia (0.5%)
Leukopenia (0.3%)
Pneumonia (0.4%)
Urinary tract infection (0.3%)
Pulmonary embolism (0.2%)
Cardiopulmonary failure (0.3%)
Stomatitis (0.3%)
Asthenia (0.2%)
Neoplasm malignant (0.2%)
Nausea (0.1%)
Peritonitis (0.1%)
Renal failure (0.1%)
Abdominal pain (0.2%)
Diarrhoea (0.2%)
Multi-organ failure (0.2%)
Pyrexia (0.2%)
Femur fracture (0.2%)
Neoplasm progression (0.2%)
Metrorrhagia (0.2%)
Haemoptysis (0.2%)
Thrombocytopenia (0.1%)
Electrolyte imbalance (0.1%)
Convulsion (0.1%)
Deep vein thrombosis (0.1%)
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Other AEs: ALT increased, AST increased...
Other AEs:
ALT increased (grade 3, 1.3%)
AST increased (grade 3, 0.8%)
AST increased (grade 4, 0.1%)
Alkaline phosphatase increased (grade 3, 0.4%)
Hyperglycemia (grade 3, 7.8%)
Hyperglycemia (grade 4, 0.6%)
Hypokalemia (grade 3, 1.4%)
Hypokalemia (grade 4, 0.4%)
Hyponatremia (grade 3, 4.9%)
Hyponatremia (grade 4, 0.6%)
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
AEs

AEs

AESignificanceDosePopulation
Headache 10.2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Anxiety 2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Dizziness 2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Euphoric mood 2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Pain in extremity 2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Palpitations 2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Somnolence 2%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Constipation 4.1%
600 mg 1 times / day single, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: single
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
healthy, mean age 32.8 years
Health Status: healthy
Age Group: mean age 32.8 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205718s000lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/25105088/
Angina pectoris 0.1%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Creatinine renal clearance decreased 0.1%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Myocardial ischaemia 0.1%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Peritonitis 0.1%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Thrombocytopenia 0.1%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Troponin increased 0.1%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
ALT increased 0.2%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Febrile neutropenia 0.2%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Leukopenia 0.2%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Platelet count decreased 0.2%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Stomatitis 0.2%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Neoplasm malignant 0.4%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Neoplasm progression 0.5%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Neutropenia 0.5%
Disc. AE
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205718Orig1s000MedR.pdf
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Convulsion 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Deep vein thrombosis 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Electrolyte imbalance 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Nausea 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Peritonitis 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Renal failure 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Thrombocytopenia 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Abdominal pain 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Asthenia 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Diarrhoea 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Femur fracture 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Haemoptysis 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Metrorrhagia 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Multi-organ failure 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Neoplasm malignant 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Neoplasm progression 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Pulmonary embolism 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Pyrexia 0.2%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Cardiopulmonary failure 0.3%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Leukopenia 0.3%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Stomatitis 0.3%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Urinary tract infection 0.3%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Pneumonia 0.4%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Anaemia 0.5%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Vomiting 0.6%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Neutropenia 1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Febrile neutropenia 1.5%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Alkaline phosphatase increased grade 3, 0.4%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
AST increased grade 3, 0.8%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
ALT increased grade 3, 1.3%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Hypokalemia grade 3, 1.4%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Hyponatremia grade 3, 4.9%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Hyperglycemia grade 3, 7.8%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
AST increased grade 4, 0.1%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Hypokalemia grade 4, 0.4%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Hyperglycemia grade 4, 0.6%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Hyponatremia grade 4, 0.6%
300 mg 1 times / 5 weeks multiple, oral
Recommended
Dose: 300 mg, 1 times / 5 weeks
Route: oral
Route: multiple
Dose: 300 mg, 1 times / 5 weeks
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
unhealthy, median age 55 years
Health Status: unhealthy
Age Group: median age 55 years
Sex: M+F
Sources:
https://www.ema.europa.eu/en/documents/assessment-report/akynzeo-epar-public-assessment-report_en.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inhibitor
2252
substrate
1193

inhibitor
2438

inducer
440
substrate
1388

inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

CYP2C19
2057

CYP2B6
926

CYP2C8
1057

P-gp
1741

MRP2
499

BSEP
550

BCRP
910

OATP1B1
1079

OATP1B3
961

OAT1
725

OAT3
747

OCT1
620

OCT2
779
CYP1A2
1197

CYP2B6
776

CYP2C8
810

CYP2C19
1119

OATP1B1
503

OATP1B3
435

OCT1
393

BCRP
697

P-gp
2052
CYP1A2
832

CYP2C19
329
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BSEP
554
 no
RO0681133
4
CYP1A2
2333
 no
CYP1A2
2333
 no
RO0681133
4
CYP1A2
2333
 no
RO0713001
4
CYP1A2
2333
 no
CYP1A2
2333
 no
RO0713001
4
CYP2C19
2141
 no
CYP2C19
2141
 no
RO0681133
4
CYP2C19
2141
 no
RO0713001
4
CYP2C19
2141
 no
CYP2C8
1117
 no
RO0713001
4
CYP2C9
2497
 no
CYP2C9
2497
 no
RO0681133
4
CYP2C9
2497
 no
RO0713001
4
CYP2C9
2497
 no
RO0713001
4
CYP2D6
2546
 no
MRP2
625
 no
MRP2
625
 no
RO0681133
4
MRP2
625
 no
RO0713001
4
OAT1
730
 no
OAT1
730
 no
RO0681133
4
OAT1
730
 no
RO0713001
4
OAT3
749
 no
OAT3
749
 no
RO0681133
4
OAT3
749
 no
RO0713001
4
OATP1B1
1095
 no
OATP1B1
1095
 no
RO0681133
4
OATP1B1
1095
 no
RO0713001
4
OATP1B3
970
 no
OATP1B3
970
 no
RO0681133
4
OATP1B3
970
 no
RO0713001
4
OCT2
782
 no
RO0681133
4
OCT2
782
 no
RO0713001
4
BCRP
985
 weak [IC50 22.6 uM]
RO0713001
4
CYP2B6
1160
 weak [IC50 23.73 uM]
RO0713001
4
CYP2C9
2497
 weak [IC50 26.41 uM]
RO0681133
4
CYP2C19
2141
 weak [IC50 33.26 uM]
RO0681133
4
CYP2D6
2546
 weak [IC50 38.84 uM]
RO0713001
4
CYP3A4
2633
 weak [IC50 39.04 uM]
RO0713001
4
CYP1A2
2333
 weak [IC50 39.39 uM]
RO0681133
4
CYP2C19
2141
 weak [IC50 57.45 uM]
RO0713001
4
BCRP
985
 weak [IC50 6 uM]
BCRP
985
 weak [IC50 8.6 uM]
RO0681133
4
BSEP
554
 weak
BSEP
554
 weak
RO0713001
4
CYP3A4
2633
 yes [IC50 1.2 uM]
RO0681133
4
OCT1
656
 yes [IC50 19 uM]
RO0681133
4
OCT2
782
 yes [IC50 22.3 uM]
CYP2C9
2497
 yes [IC50 22.6 uM]
CYP2B6
1160
 yes [IC50 33.38 uM]
CYP2C8
1117
 yes [IC50 4.74 uM]
RO0681133
4
CYP2B6
1160
 yes [IC50 4.89 uM]
RO0681133
4
P-gp
1932
 yes [IC50 4.95 uM]
RO0681133
4
CYP2C8
1117
 yes [IC50 50.4 uM]
OCT1
656
 yes [IC50 7.4 uM]
RO0713001
4
OCT1
656
 yes [IC50 7.9 uM]
P-gp
1932
 yes [IC50 8 uM]
RO0713001
4
CYP2D6
2546
 yes [IC50 8.54 uM]
RO0681133
4
CYP3A4
2633
 yes [Ki 1.1 uM]
P-gp
1932
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
697
 no
BCRP
697
 no
RO0681133
4
BCRP
697
 no
RO0713001
4
CYP1A2
1197
 no
CYP2B6
776
 no
CYP2C19
1119
 no
CYP2C8
810
 no
OATP1B1
503
 no
OATP1B1
503
 no
RO0681133
4
OATP1B1
503
 no
RO0713001
4
OATP1B3
435
 no
OATP1B3
435
 no
RO0681133
4
OATP1B3
435
 no
RO0713001
4
OCT1
393
 no
OCT1
393
 no
RO0681133
4
OCT1
393
 no
RO0713001
4
CYP2C9
1193
 yes
CYP2D6
1388
 yes
P-gp
2052
 yes
RO0681133
4
P-gp
2052
 yes
RO0713001
4
CYP3A4
1946
 yes
yes (co-administration study)
Comment: Administration of the CYP3A4 inhibitor ketoconazole with netupitant/palonosetron FDC increased the exposure of netupitant and resulted in an AUC0-tz of 1.8 fold, AUC0-’ of 2.4 fold, and Cmax of 1.3 fold when compared to the administration of netupitant/palonosetron FDC alone.
Page: 73.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:85155
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85155
ChemicalBook
CB71483126
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB71483126
MolPort
MolPort-019-904-423
https://www.molport.com/shop/molecule-link/MolPort-019-904-423
ZINC
ZINC000011681563
http://zinc15.docking.org/substances/ZINC000011681563
PubMed

PubMed

TitleDatePubMed
Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy.
2018-07-01
Differential and additive suppressive effects of 5-HT3 (palonosetron)- and NK1 (netupitant)-receptor antagonists on cisplatin-induced vomiting and ERK1/2, PKA and PKC activation.
2015-04
A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.
2014-07
Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy-induced emesis.
2006-04-01
Efficient synthesis of novel NK1 receptor antagonists: selective 1,4-addition of grignard reagents to 6-chloronicotinic acid derivatives.
2006-03-03
Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists.
2006-03-01
Patents

Patents

06479483
5
08426450
5
US2003004157
4
US2003083345
4
US2005107380
4
US2006247240
4
US2008085884
4
US20180291049A1
4
US6297375
4
US6479483
4
US7211579
4
US7288658
4
US7384939
4

Sample Use Guides

In Vivo Use Guide
One AKYNZEO (netupitant and palonosetron) capsule administered approximately 1 hour prior to the start of chemotherapy with dexamethasone 12 mg administered orally 30 minutes prior to chemotherapy on day 1 and 8 mg orally once daily on days 2 to 4 (for highly emetogenic chemotherapy, including cisplatin based chemotherapy) or on day 1 with not necessary administration of dexamethasone on days 2 to 4 (for anthracyclines and cyclophosphamide based chemotherapy and chemotherapy not considered highly emetogenic)
Route of Administration: Oral
In Vitro Use Guide
HEK-293 cells were incubated with 5 nM [3H]-netupitant for 40 min at room temperature.
Substance Class Chemical
Created
by admin
on Wed Apr 02 06:53:43 GMT 2025
Edited
by admin
on Wed Apr 02 06:53:43 GMT 2025
Record UNII
7732P08TIR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NETUPITANT
DASH   INN   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
RO-67-3189
Preferred Name English
NETUPITANT COMPONENT AKYNZEO CAPSULE
Brand Name English
NETUPITANT [USAN]
Common Name English
NETUPITANT [ORANGE BOOK]
Common Name English
netupitant [INN]
Common Name English
Netupitant [WHO-DD]
Common Name English
AKYNZEO CAPSULE COMPONENT NETUPITANT
Brand Name English
RO-67-3189/000
Code English
BENZENEACETAMIDE, N,.ALPHA.,.ALPHA.-TRIMETHYL-N-(4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-3-PYRIDINYL)-3,5-BIS(TRIFLUOROMETHYL)-
Systematic Name English
RO 67-3189/000
Code English
2-[3,5-Bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide
Systematic Name English
RO-673189000
Code English
NETUPITANT [VANDF]
Common Name English
NETUPITANT [MI]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS AKYNZEO (AUTHORIZED: NAUSEA)
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
NDF-RT N0000175786
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
NCI_THESAURUS C267
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
Code System Code Type Description
SMS_ID
100000156565
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
PUBCHEM
6451149
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
USAN
RR-56
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
INN
8409
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
FDA UNII
7732P08TIR
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
DAILYMED
7732P08TIR
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
ChEMBL
CHEMBL206253
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
CHEBI
85155
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
NDF-RT
N0000190113
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
CAS
290297-26-6
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
DRUG CENTRAL
4898
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
NDF-RT
N0000182141
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
NDF-RT
N0000185503
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY P-Glycoprotein Inhibitors [MoA]
EVMPD
SUB130488
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
WIKIPEDIA
Netupitant
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
EPA CompTox
DTXSID50183271
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
IUPHAR
5742
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
DRUG BANK
DB09048
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
NCI_THESAURUS
C96745
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
MESH
C508854
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
RXCUI
1552337
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY RxNorm
MERCK INDEX
m11791
Created by admin on Wed Apr 02 06:53:43 GMT 2025 , Edited by admin on Wed Apr 02 06:53:43 GMT 2025
PRIMARY
Related Record Type Details
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
Netupitnat: Cmax/IC50= (1-1.5μM)/6 μM = (0.167-0.25)>0.1
Structure of NETUPITANT DIHYDROCHLORIDE
SALT/SOLVATE -> PARENT
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SUBSTANCE-P RECEPTOR
TARGET -> INHIBITOR
Related Record Type Details
Structure of RO-0681133
METABOLITE ACTIVE -> PARENT
of parent exposure
MAJOR
AUC
Structure of RO-0731519
METABOLITE ACTIVE -> PARENT
of parent exposure
MAJOR
AUC
Structure of FOSNETUPITANT
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
Structure of NETUPITANT
ACTIVE MOIETY
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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