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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H21F7N4O3
Molecular Weight 534.4267
Optical Activity ( + )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APREPITANT

SMILES

C[C@@H](O[C@H]1OCCN(CC2=NC(=O)NN2)[C@H]1C3=CC=C(F)C=C3)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F

InChI

InChIKey=ATALOFNDEOCMKK-OITMNORJSA-N
InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1

HIDE SMILES / InChI

Molecular Formula C23H21F7N4O3
Molecular Weight 534.4267
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021549s025lbl.pdf

Fosaprepitant (Emend for Injection (US), Ivemend (EU)) is a prodrug of Aprepitant. Once biologically activated, the drug acts as a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. In summary, the active form of fosaprepitant is as an NK1 antagonist which is because it blocks signals given off by NK1 receptors. This therefore decreases the likelihood of vomiting in patients experiencing. Fosaprepitant is used for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
EMEND

Approved Use

1.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) EMEND, in combination with other antiemetic agents, is indicated for the: prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Prevention of Postoperative Nausea and Vomiting (PONV): EMEND is indicated for the prevention of postoperative nausea and vomiting

Launch Date

2006
Preventing
EMEND

Approved Use

1.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) EMEND, in combination with other antiemetic agents, is indicated for the: prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Prevention of Postoperative Nausea and Vomiting (PONV): EMEND is indicated for the prevention of postoperative nausea and vomiting

Launch Date

2006
Secondary
EMEND

Approved Use

EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist, indicated: • in combination with other antiemetic agents in patients 12 years of age and older and patients less than 12 years of age who weight at least 30 kg for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1) • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (1.1) • for prevention of postoperative nausea and vomiting (PONV) in adults (1.2)

Launch Date

2008
Preventing
EMEND

Approved Use

EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist, indicated: • in combination with other antiemetic agents in patients 12 years of age and older and patients less than 12 years of age who weight at least 30 kg for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1) • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (1.1) • for prevention of postoperative nausea and vomiting (PONV) in adults (1.2)

Launch Date

2008
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1354 ng/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
4.3 μg/mL
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
6.1 μg/mL
130 mg single, intravenous
dose: 130 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
44578 ng × h/mL
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSAPREPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
27759 ng × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
27.8 μg × h/mL
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
43.9 μg × h/mL
130 mg single, intravenous
dose: 130 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
APREPITANT unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.2 min
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSAPREPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14 h
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSAPREPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
125 mg single, oral
Dose: 125 mg
Route: oral
Route: single
Dose: 125 mg
Sources:
unhealthy, 53 years (range: 23-73 years)
n = 64
Health Status: unhealthy
Condition: Cough
Age Group: 53 years (range: 23-73 years)
Sex: M+F
Population Size: 64
Sources:
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources: Page: p. 27
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources: Page: p. 27
Disc. AE: Dyspnea, Nerve injury, peripheral...
AEs leading to
discontinuation/dose reduction:
Dyspnea (2 patients)
Nerve injury, peripheral (1 patient)
Dyspnea (1 patient)
Hyperhidrosis (1 patient)
Sources: Page: p. 27
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Other AEs: Constipation, Diarrhea...
Other AEs:
Constipation (below serious, 14 patients)
Diarrhea (below serious, 7 patients)
Dry mouth (below serious, 7 patients)
Abdominal pain (below serious, 13 patients)
Weakness (below serious, 18 patients)
Nightmares (below serious, 2 patients)
Sleepiness (below serious, 2 patients)
Sweating (below serious, 8 patients)
Pain in extremity (below serious, 5 patients)
Dizziness (below serious, 7 patients)
Nervousness (below serious, 10 patients)
Nightmares (below serious, 2 patients)
Depression (below serious, 2 patients)
Sexual dysfunction (below serious, 3 patients)
Sources:
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Other AEs: Hypoglycemia, Bruising...
Other AEs:
Hypoglycemia (serious, 1 patient)
Bruising (below serious, 1 patient)
Gastrointestinal pain (below serious, 3 patients)
Hypokalemia (below serious, 1 patient)
Diarrhea (below serious, 1 patient)
Musculoskeletal pain (below serious, 1 patient)
Fainting (below serious, 1 patient)
Renal bleeding (below serious, 1 patient)
Fibromyalgia (below serious, 1 patient)
Dizziness (below serious, 2 patients)
Constipation (below serious, 1 patient)
Rhinitis (below serious, 1 patient)
Headache (below serious, 2 patients)
Malaise (below serious, 1 patient)
Pain in limb (below serious, 1 patient)
Nosebleed (below serious, 1 patient)
Sources:
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Other AEs: Anemia, Clot blood...
Other AEs:
Anemia (serious, 1 patient)
Clot blood (serious, 1 patient)
Hospital acquired pneumonia (serious, 1 patient)
Headache (below serious, 2 patients)
Hot flashes (below serious, 2 patients)
Nausea (below serious, 2 patients)
Paresthesia (below serious, 2 patients)
Wound dehiscence (below serious, 2 patients)
Wound infection (below serious, 6 patients)
Sources:
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources:
healthy, 33
n = 50
Health Status: healthy
Age Group: 33
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Dyspnea...
AEs leading to
discontinuation/dose reduction:
Dyspnea (2%)
Sources:
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Disc. AE: Hypersensitivity reaction, Anaphylaxis...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity reaction
Anaphylaxis
Anaphylactic shock
Infusion site reactions
Thrombophlebitis
Necrosis
Vasculitis
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Dyspnea 1 patient
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources: Page: p. 27
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources: Page: p. 27
Hyperhidrosis 1 patient
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources: Page: p. 27
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources: Page: p. 27
Nerve injury, peripheral 1 patient
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources: Page: p. 27
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources: Page: p. 27
Dyspnea 2 patients
Disc. AE
130 mg single, intravenous
Recommended
Dose: 130 mg
Route: intravenous
Route: single
Dose: 130 mg
Sources: Page: p. 27
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources: Page: p. 27
Nervousness below serious, 10 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Abdominal pain below serious, 13 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Constipation below serious, 14 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Weakness below serious, 18 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Depression below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Nightmares below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Nightmares below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Sleepiness below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Sexual dysfunction below serious, 3 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Pain in extremity below serious, 5 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Diarrhea below serious, 7 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Dizziness below serious, 7 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Dry mouth below serious, 7 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Sweating below serious, 8 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 30
Health Status: unhealthy
Condition: Post traumatic stress disorder
Population Size: 30
Sources:
Bruising below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Constipation below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Diarrhea below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Fainting below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Fibromyalgia below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Hypokalemia below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Malaise below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Musculoskeletal pain below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Nosebleed below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Pain in limb below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Renal bleeding below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Rhinitis below serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Dizziness below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Headache below serious, 2 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Gastrointestinal pain below serious, 3 patients
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Hypoglycemia serious, 1 patient
125 mg 1 times / day steady, oral
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy
n = 63
Health Status: unhealthy
Condition: Chronic Nausea and Vomiting
Population Size: 63
Sources:
Headache below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Hot flashes below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Nausea below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Paresthesia below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Wound dehiscence below serious, 2 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Wound infection below serious, 6 patients
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Anemia serious, 1 patient
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Clot blood serious, 1 patient
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Hospital acquired pneumonia serious, 1 patient
40 mg single, oral
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy
n = 34
Health Status: unhealthy
Condition: Gynecologic Surgery Population
Population Size: 34
Sources:
Dyspnea 2%
Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources:
healthy, 33
n = 50
Health Status: healthy
Age Group: 33
Sex: M+F
Population Size: 50
Sources:
Anaphylactic shock Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Anaphylaxis Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Hypersensitivity reaction Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Infusion site reactions Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Necrosis Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Thrombophlebitis Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
Vasculitis Disc. AE
150 mg single, intravenous
Recommended
Dose: 150 mg
Route: intravenous
Route: single
Dose: 150 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy
Sources: Page: p.1
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate
yes (co-administration study)
Comment: 2.3 to 3.3 fold increase in mean AUC of orally coadministered midazolam;
Page: 7.0
no
unlikely
unlikely
unlikely
weak [IC50 44.7 uM]
weak [IC50 >100 uM]
weak [IC50 >100 uM]
weak [IC50 >100 uM]
weak [IC50 >100 uM]
weak [Ki 108 uM]
weak [Ki 66 uM]
weak
yes (co-administration study)
Comment: fosaprepitant increased the AUC of midazolam by 1.8-fold; fosaprepitant increased diltiazem AUC by 1.4-fold
Page: 15, 16
yes
yes
yes
weak (co-administration study)
Comment: no effect of drug on the plasma AUC of R(+) and S(-) warfarin; coadministration with tolbutamide (substrate) decreased AUC of tolbutamide by 23% (Day 4), 28% (Day 8), and 15% (Day 15);
Page: 7.0
yes
yes (co-administration study)
Comment: oral aprepitant decreased the AUC of tolbutamide by 23% on Day 4; fosaprepitant/aprepitant decreased warfarin exposure and prolongation of prothrombin time
Page: 9, 15
yes
yes (co-administration study)
Comment: fosaprepitant/aprepitant increased pimozide exposure; fosaprepitant/aprepitant increased midazolam exposure; fosaprepitant/aprepitant increased dexamethazone exposure; ifosaprepitant/aprepitant increased methylprednisolone exposure
Page: 8.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: coadministration with ketoconazole (inhibitor) increased AUC of aprepitant by ~5-fold; coadministration with rifampin (inducer) decreased AUC of aprepitant by ~ 11-fold;
Page: 2.0
major
yes (co-administration study)
Comment: ketoconazole completely inhibited metabolism of MK-0869
Page: 8, 12
minor
minor
minor
no
no
no
no
no
no
weak
no (co-administration study)
Comment: lack of interaction between aprepitant with digoxin in clinical drug interaction study
Page: 72.0
PubMed

PubMed

TitleDatePubMed
Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs.
2000 Mar 23
Central neurocircuitry associated with emesis.
2001 Dec 3
Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.
2007 Dec
Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects.
2007 Jul
Fosaprepitant dimeglumine (MK-0517 or L-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting.
2008 Dec
Recent trends in the impurity profile of pharmaceuticals.
2010 Jul
Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting.
2010 Oct 21
Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy.
2011 Aug
Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC).
2011 Sep
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: can also be infused IV http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206197Orig1s000lbl.pdf
Prevention of Chemotherapy Induced Nausea and Vomiting: 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg orally once daily in the morning on Days 2 and 3. The package insert for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with EMEND (aprepitant capsules). Prevention of Postoperative Nausea and Vomiting: The recommended oral dosage of EMEND is 40 mg within 3 hours prior to induction of anesthesia EMEND may be taken with or without food.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Aprepitant suppressed HIV Bal infection of macrophages. Treatment with aprepitant (10(-6) M) inhibited infection of macrophages with the AZT- resistant viruses (A018, A012) by 0.7 log(10). Aprepitant also suppressed infection of macrophages with RT inhibitor-resistant virus (TC 49 and TC 60) by 0.5 log(10). Furthermore, aprepitant significantly enhanced the anti-HIV activity of antiretrovirals (AZT, Efavirenz, and Indinavir) in HIV Bal-infected macrophages, and aprepitant inhibited CCR5 expression on macrophages, ranging from 50.5 to 29.6%. Donor heterogeneity was observed in antiviral activity and CCR5 receptor expression.
Monocytes isolated from healthy donors were cultured for 7 days and then treated with or without aprepitant (10(-6) M) for 2 h, followed by HIV infection with drug-resistant strains for 2 h.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:37:45 GMT 2023
Edited
by admin
on Fri Dec 15 15:37:45 GMT 2023
Record UNII
1NF15YR6UY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
APREPITANT
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
EMEND
Brand Name English
MK-0869
Code English
L-754,030
Code English
APREPITANT [EMA EPAR]
Common Name English
APREPITANT [USP-RS]
Common Name English
APREPITANT [VANDF]
Common Name English
aprepitant [INN]
Common Name English
APREPITANT [ORANGE BOOK]
Common Name English
APREPITANT [EP MONOGRAPH]
Common Name English
APREPITANT [MART.]
Common Name English
APONVIE
Brand Name English
3H-1,2,4-TRIAZOL-3-ONE, 5-(((2R,3S)-2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-1,2-DIHYDRO-
Systematic Name English
Aprepitant [WHO-DD]
Common Name English
NSC-748825
Code English
CINVANTI
Brand Name English
3-(((2R,3S)-3-(P-FLUOROPHENYL)-2-(((.ALPHA.R)-.ALPHA.-METHYL-3,5-BIS(TRIFLUOROMETHYL)BENZYL)OXY)MORPHOLINO)METHYL)-.DELTA.(SUP 2)-1,2,4-TRIAZOLIN-5-ONE.
Common Name English
APREPITANT [USP MONOGRAPH]
Common Name English
MK-869
Code English
APREPITANT [USAN]
Common Name English
ONO-7436
Code English
APREPITANT [JAN]
Common Name English
APREPITANT [MI]
Common Name English
Classification Tree Code System Code
WHO-VATC QA04AD12
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
EMA ASSESSMENT REPORTS EMEND (AUTHORIZED: POSTOPERATIVE NAUSEA AND VOMITTING)
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
NDF-RT N0000175786
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
EMA ASSESSMENT REPORTS EMEND (AUTHORIZED: VOMITTING)
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
LIVERTOX NBK548897
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
NDF-RT N0000010262
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
NCI_THESAURUS C267
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
WHO-ATC A04AD12
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
Code System Code Type Description
USAN
LL-96
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
RS_ITEM_NUM
1041904
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
NDF-RT
N0000185506
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
PUBCHEM
135413536
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
IUPHAR
3490
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
NDF-RT
N0000182141
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
WIKIPEDIA
APREPITANT
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
NCI_THESAURUS
C49173
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
NDF-RT
N0000185507
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY Cytochrome P450 2C9 Inducers [MoA]
DRUG CENTRAL
230
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
MERCK INDEX
m2011
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY Merck Index
CAS
170729-80-3
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
INN
8050
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
DRUG BANK
DB00673
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
DAILYMED
1NF15YR6UY
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
CHEBI
499361
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
ChEMBL
CHEMBL1471
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
EVMPD
SUB20017
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
MESH
C114556
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
NSC
748825
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
SMS_ID
100000089541
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
RXCUI
358255
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY RxNorm
EPA CompTox
DTXSID3049047
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
FDA UNII
1NF15YR6UY
Created by admin on Fri Dec 15 15:37:45 GMT 2023 , Edited by admin on Fri Dec 15 15:37:45 GMT 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted.
METABOLIC ENZYME -> SUBSTRATE
MINOR
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY GENOTOXIC->PARENT
Potentially genotoxic N-nitorso
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC