Fosaprepitant

Identification

Name
Fosaprepitant
Accession Number
DB06717
Description

Fosaprepitant is an intravenously administered antiemetic drug. It is a prodrug of Aprepitant. It aids in the prevention of acute and delayed nausea and vomiting associated with chemotherapy treatment.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 614.4066
Monoisotopic: 614.116518403
Chemical Formula
C23H22F7N4O6P
Synonyms
  • Fosaprépitant
  • Fosaprepitant
  • Fosaprepitantum
External IDs
  • L-758,298
  • L-758298

Pharmacology

Indication

For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Fosaprepitant 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).

Mechanism of action

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.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding

95% +

Metabolism

Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma.

Route of elimination

Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.

Half-life

9-13 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Fosaprepitant can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Fosaprepitant can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Fosaprepitant.
AcalabrutinibThe metabolism of Fosaprepitant can be increased when combined with Acalabrutinib.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Fosaprepitant.
AcetaminophenThe metabolism of Fosaprepitant can be increased when combined with Acetaminophen.
AcetazolamideThe metabolism of Fosaprepitant can be decreased when combined with Acetazolamide.
AdalimumabThe metabolism of Fosaprepitant can be increased when combined with Adalimumab.
AlbendazoleThe metabolism of Albendazole can be increased when combined with Fosaprepitant.
AldesleukinThe metabolism of Fosaprepitant can be decreased when combined with Aldesleukin.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity
    Available for Purchase

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level
    Available for Purchase

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Exercise caution with grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of fosaprepitant, which may increase its serum concentration.
  • Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of fosaprepitant and may reduce its serum concentration.

Products

Purchasing individual compounds or compound libraries for your research?
Learn More
Product Ingredients
IngredientUNIICASInChI Key
Fosaprepitant dimeglumineD35FM8T64X265121-04-8VRQHBYGYXDWZDL-OOZCZQCLSA-N
Active Moieties
NameKindUNIICASInChI Key
Aprepitantprodrug1NF15YR6UY170729-80-3ATALOFNDEOCMKK-OITMNORJSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EmendInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMerck Sharp & Dohme Corp.2017-02-03Not applicableUS flag
EmendInjection, powder, lyophilized, for solution115 mg/5mLIntravenousMerck Sharp & Dohme Limited2008-01-252012-07-31US flag
EmendInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMerck Sharp & Dohme Limited2010-11-12Not applicableUS flag
Emend IVPowder, for solutionIntravenousMerck Ltd.2009-04-302010-10-28Canada flag
Emend IVPowder, for solutionIntravenousMerck Ltd.2011-04-04Not applicableCanada flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/1IntravenousActavis Pharma, Inc.2019-09-19Not applicableUS flag
FosaprepitantPowder, for solution150 mgIntravenousApotex CorporationNot applicableNot applicableCanada flag
IvemendInjection, powder, for solution150 mgIntravenousMerck Sharp & Dohme B.V.2008-01-11Not applicableEU flag
IvemendInjection, powder, for solution150 mgIntravenousMerck Sharp & Dohme B.V.2008-01-11Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousDr. Reddy's Laboratories Inc.,2020-07-01Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMsn Laboratories Private Limited2019-09-05Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousBluePoint Laboratories2019-11-20Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousBE Pharmaceuticals Inc.2019-10-15Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousNovadoz Pharmaceuticals Llc2019-09-05Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution115 mg/5mLIntravenousMylan Institutional LLC2019-09-05Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMeitheal Pharmaceuticals Inc.2019-11-15Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousLupin Pharmaceuticals, Inc.2020-09-25Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousCipla USA Inc.2019-09-05Not applicableUS flag
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMsn Laboratories Private Limited2020-02-10Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazinanes
Sub Class
Morpholines
Direct Parent
Phenylmorpholines
Alternative Parents
Trifluoromethylbenzenes / Fluorobenzenes / Aralkylamines / Aryl fluorides / Triazoles / Heteroaromatic compounds / Trialkylamines / Oxacyclic compounds / Azacyclic compounds / Acetals
show 5 more
Substituents
1,2,4-triazole / Acetal / Alkyl fluoride / Alkyl halide / Amine / Aralkylamine / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines, triazoles, phosphoramide, (trifluoromethyl)benzenes, cyclic acetal (CHEBI:64321)

Chemical Identifiers

UNII
6L8OF9XRDC
CAS number
172673-20-0
InChI Key
BARDROPHSZEBKC-OITMNORJSA-N
InChI
InChI=1S/C23H22F7N4O6P/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)40-20-19(13-2-4-17(24)5-3-13)33(6-7-39-20)11-18-31-21(35)34(32-18)41(36,37)38/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H,31,32,35)(H2,36,37,38)/t12-,19+,20-/m1/s1
IUPAC Name
(3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-5-oxo-2,5-dihydro-1H-1,2,4-triazol-1-yl)phosphonic acid
SMILES
C[[email protected]@H](O[[email protected]]1OCCN(CC2=NC(=O)N(N2)P(O)(O)=O)[[email protected]]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F

References

Synthesis Reference

Navin Ganesh Bhatt, Nikhil Rasiklal Trivedi, Mahesh Khedekar, Sukumar Sinha, Mubeen Ahmed Khan, Ramjilal Yadav, "FOSAPREPITANT DIMEGLUMINE INTERMEDIATE, NEUTRAL FOSAPREPITANT, AND AMORPHOUS FOSAPREPITANT DIMEGLUMINE AND PROCESSES FOR THEIR PREPARATIONS." U.S. Patent US20110130366, issued June 02, 2011.

US20110130366
General References
Not Available
Human Metabolome Database
HMDB0015662
KEGG Drug
D06597
PubChem Compound
219090
PubChem Substance
99443269
ChemSpider
189912
RxNav
1731071
ChEBI
64321
ChEMBL
CHEMBL1199324
ZINC
ZINC000003939013
PharmGKB
PA165958390
Wikipedia
Fosaprepitant
AHFS Codes
  • 56:22.92 — Miscellaneous Antiemetics
  • 56:22.32 — Neurokinin-1 Receptor Antagonists

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
4CompletedTreatmentOvarian Cancer / Uterine Malignancies1
4RecruitingPreventionPost Operative Nausea and Vomiting (PONV)1
4RecruitingTreatmentNausea, Postoperative1
3CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)3
3CompletedSupportive CareGenital Neoplasms, Female / Nausea / Vomiting1
3CompletedSupportive CareHematopoietic/Lymphoid Cancer / Nausea and vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
3Not Yet RecruitingSupportive CareGynecologic Cancers1
3Not Yet RecruitingSupportive CareSolid Tumor Patients Receiving High Emetic Risk Multi-day Chemotherapy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous150 mg
Injection, powder, lyophilized, for solutionIntravenous115 mg/5mL
Injection, powder, lyophilized, for solutionIntravenous150 mg/5mL
Powder, for solutionIntravenous
Injection, solutionIntravenous150 mg
Injection, powder, lyophilized, for solutionIntravenous150 mg/1
Powder, for solutionIntravenous150 mg
Injection, powder, for solutionParenteral150 mg
Injection, solution, concentrateIntravenous150 mg
Injection, powder, for solutionIntravenous115 mg
Injection, powder, for solutionIntravenous150 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5691336Yes1997-11-252019-09-04US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00632 mg/mLALOGPS
logP2.89ALOGPS
logP2.4ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)1.02ChemAxon
pKa (Strongest Basic)5.69ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area123.93 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity138.63 m3·mol-1ChemAxon
Polarizability49.92 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.5225
Blood Brain Barrier-0.81
Caco-2 permeable-0.6534
P-glycoprotein substrateSubstrate0.8255
P-glycoprotein inhibitor INon-inhibitor0.6532
P-glycoprotein inhibitor IINon-inhibitor0.986
Renal organic cation transporterNon-inhibitor0.8583
CYP450 2C9 substrateNon-substrate0.7018
CYP450 2D6 substrateNon-substrate0.8588
CYP450 3A4 substrateSubstrate0.546
CYP450 1A2 substrateNon-inhibitor0.7539
CYP450 2C9 inhibitorNon-inhibitor0.644
CYP450 2D6 inhibitorNon-inhibitor0.8521
CYP450 2C19 inhibitorNon-inhibitor0.6705
CYP450 3A4 inhibitorInhibitor0.6258
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.5349
CarcinogenicityNon-carcinogens0.7701
BiodegradationNot ready biodegradable0.9899
Rat acute toxicity2.6064 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.6528
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Dushenkov A, Kalabalik J, Carbone A, Jungsuwadee P: Drug interactions with aprepitant or fosaprepitant: Review of literature and implications for clinical practice. J Oncol Pharm Pract. 2017 Jun;23(4):296-308. doi: 10.1177/1078155216631408. Epub 2016 Feb 25. [PubMed:26921085]
  2. Fosaprepitant FDA label [File]

Drug created on May 16, 2010 18:16 / Updated on November 25, 2020 15:47

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates