pharmacopeia
GET
/api/v1/drug/aprepitant
2D structure
3-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,4-dihydro-1,2,4-triazol-5-one
SMILES C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)O[C@@H]2[C@@H](N(CCO2)CC3=NNC(=O)N3)C4=CC=C(C=C4)F
InChIKey ATALOFNDEOCMKK-OITMNORJSA-N

Mechanism of action

Sourced from openFDA

Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK 1 ) receptors. Aprepitant has little or no affinity for serotonin (5-HT 3 ), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).

Cytochrome P450 3A4Neurokinin 1

Indications

Sourced from openFDA
  • Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist. Aprepitant capsules are indicated • in combination with other antiemetic agents, in patients 12 years of age and older for prevention of: o acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin ( 1.1 ) o 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 ) Limitations of Use : ( 1.3 ) • Aprepitant has not been studied for treatment of established nausea and vomiting.ICD-10: R11.2

Contraindications

Sourced from openFDA
  • Aprepitant is contraindicated in patients: • who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions ( 6.2 )] .contraindicated

Dosage & administration

Sourced from openFDA

Recommended Dosage for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) ( 2.1 ) •Aprepitant capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3. • Administer aprepitant 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer aprepitant in morning. See Full Prescribing Information for recommended dosages of concomitant dexamethasone and 5-HT 3 antagonist for HEC and MEC. Recommended Dosage for PONV ( 2.2 ) • Adults: 40 mg Aprepitant capsules within 3 hours prior to induction of anesthesia. Preparation and Administration ( 2.3 ) • Aprepitant capsules can be administered with or without food. • Swallow aprepitant capsules whole. • For details on preparation see Full Prescribing Information. 2.1 Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) Adults and Pediatric Patients 12 Years of Age and Older The recommended oral dosage of aprepitant capsules, dexamethasone, and a 5-HT 3 antagonist in adults and pediatric patients 12 years of age and older who can swallow oral capsules, for the prevention of nausea and vomiting associated with administration of HEC or MEC is shown in Table 1 or Table 2, respectively.

Warnings & precautions

Sourced from openFDA

• CYP3A4 Interactions : Aprepitant is a substrate, weak-to-moderate inhibitor and inducer of CYP3A4; See Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustments of aprepitant and concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 ) • Warfarin (a CYP2C9 substrate) : Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following initiation of aprepitant. ( 5.2 , 7.1 ) • Hormonal Contraceptives : Efficacy of contraceptives may be reduced during administration of and for 28 days following the last dose of aprepitant. Use effective alternative or back-up methods of contraception. ( 5.3 , 7.1 , 8.3 ) 5.1 Clinically Significant CYP3A4 Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use of aprepitant with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug. Use of pimozide with aprepitant is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide [see Contraindications ( 4 )] . Use of aprepitant with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma conentrations of aprepitant and result in an increased risk of adverse reactions related to aprepitant.

Adverse reactions

Sourced from openFDA

Most common adverse reactions (≥3%) are ( 6.1 ): Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) • Adults: fatigue, diarrhea, asthenia, dyspepsia, abdominal pain, hiccups, white blood cell count decreased, dehydration, and alanine aminotransferase increased. • Pediatrics: neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness, and hiccups. PONV • Adults: constipation and hypotension. To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The overall safety of aprepitant was evaluated in approximately 6,800 individuals. Adverse Reactions in Adults in the Prevention of Nausea and Vomiting Associated with HEC and MEC In 2 active-controlled, double-blind clinical trials in patients receiving highly emetogenic chemotherapy (HEC) (Studies 1 and 2), aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) was compared to ondansetron and dexamethasone alone (standard therapy [see Clinical Studies ( 14.1 )].

Use in specific populations

Sourced from openFDA

8.1 PREGNANCY Risk Summary There are insufficient data on use of aprepitant in pregnant women to inform a drug associated risk. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (AUC) approximately 1.5 times the adult human exposure at the 125-mg/80-mg/ 80-mg aprepitant regimen [see Data] . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryofetal development studies in rats and rabbits, aprepitant was administered during the period of organogenesis at oral doses up to 1,000 mg/kg twice daily in rats and up to the maximum tolerated dose of 25 mg/kg/day in rabbits. No embryofetal lethality or malformations were observed at any dose level in either species. The exposures (AUC) in pregnant rats at 1,000 mg/kg twice daily and in pregnant rabbits at 125 mg/kg/day were approximately 1.5 times the adult exposure at the 125-mg/80mg/80-mg aprepitant regimen. Aprepitant crosses the placenta in rats and rabbits.

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption Following oral administration of a single 40-mg dose of aprepitant in the fasted state, mean area under the plasma concentration-time curve (AUC 0 - ∞ ) was 7.8 mcg•hr/mL and mean peak plasma concentration (C max ) was 0.7 mcg/mL, occurring at approximately 3 hours postdose (T max ). The absolute bioavailability at the 40-mg dose has not been determined.

Overdosage

Sourced from openFDA

No specific information is available on the treatment of overdosage. Drowsiness and headache were reported in one patient who ingested 1,440 mg of aprepitant (approximately 11 times the maximum recommended single dose). In the event of overdose, aprepitant should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of aprepitant, drug-induced emesis may not be effective in cases of aprepitant overdosage. Aprepitant is not removed by hemodialysis.

Approval history

Sourced from openFDA
  • Mar 26, 2003NDANDA021549Msd
  • Sep 24, 2012ANDAANDA090999Sandoz
  • Dec 17, 2015NDANDA207865Msd Merck Co
  • Oct 12, 2017ANDAANDA207777Glenmark Speclt
  • Nov 9, 2017NDANDA209296Heron Theraps Inc
  • Oct 21, 2020ANDAANDA211835Torrent
  • Sep 16, 2022NDANDA216457Heron Theraps Inc

FDA shortages

View JSON

Reference statistics from the openFDA drug-shortage dataset. For a live view, consult the FDA database directly. Not clinical guidance.

  • Emend, Oral Powder for Suspension, 125 mg (NDC 0006-3066-03)To be discontinued
    Sponsor: Merck Sharp & Dohme LLC
    Updated

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
18,081 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Nausea2,18612%
  2. 2Fatigue1,85410%
  3. 3Pyrexia1,6249.0%
  4. 4Diarrhoea1,5838.8%
  5. 5Dyspnoea1,5488.6%
  6. 6Vomiting1,5128.4%
  7. 7Off Label Use1,3887.7%
  8. 8Alopecia1,3047.2%
  9. 9Rash1,2446.9%
  10. 10Hypersensitivity1,1646.4%
  11. 11Decreased Appetite1,0705.9%
  12. 12Febrile Neutropenia1,0615.9%
  13. 13Pruritus1,0525.8%
  14. 14Stomatitis1,0165.6%
  15. 15Infusion Related Reaction1,0115.6%

Literature

View JSON

Recent PubMed references pinned to Aprepitant as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

View JSON

The 10 most recently updated of 220 ClinicalTrials.gov registrations naming Aprepitant as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Aprepitant work?
Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK 1 ) receptors. Aprepitant has little or no affinity for serotonin (5-HT 3 ), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).
What is Aprepitant used for?
According to FDA labeling, Aprepitant carries indications including: Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist. Aprepitant capsules are indicated • in combination with other antiemetic agents, in patients 12 years of age and older for prevention of: o acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin ( 1.1 ) o 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 ) Limitations of Use : ( 1.3 ) • Aprepitant has not been studied for treatment of established nausea and vomiting.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Aprepitant?
Aprepitant is classified as Other antiemetics, Substance P/Neurokinin-1 Receptor Antagonist, Cytochrome P450 2C9 Inducers, Cytochrome P450 3A4 Inducers, Cytochrome P450 3A4 Inhibitors, Neurokinin 1 Antagonists, Decreased Brain Stem Substance P Activity, Decreased Kinin Activity, Emesis Suppression.
What are the brand names for Aprepitant?
Aprepitant is marketed under brand names including Aponvie, Cinvanti, Emend.
What are the contraindications for Aprepitant?
Aprepitant labeling lists contraindications including: Aprepitant is contraindicated in patients: • who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions ( 6.2 )] .. Always consult the full prescribing information and a clinician.
Note. Data for aprepitant is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

Search pharmacopeia

Search drugs, classes, and ingredients