Identification

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Name
Fosaprepitant
Accession Number
DB06717
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • Fosaprépitant
  • Fosaprepitant
  • Fosaprepitantum
External IDs
L-758,298 / L-758298
Product Ingredients
IngredientUNIICASInChI Key
Fosaprepitant dimeglumineD35FM8T64X265121-04-8VRQHBYGYXDWZDL-OOZCZQCLSA-N
Active Moieties
NameKindUNIICASInChI Key
Aprepitantprodrug1NF15YR6UY170729-80-3ATALOFNDEOCMKK-OITMNORJSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EmendInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMerck Sharp & Dohme Limited2010-11-12Not applicableUs
EmendInjection, powder, lyophilized, for solution115 mg/5mLIntravenousMerck Sharp & Dohme Limited2008-01-252012-07-31Us
EmendInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMerck Sharp & Dohme Corp.2017-02-03Not applicableUs
Emend IVPowder, for solutionIntravenousMerck Ltd.2009-04-302010-10-28Canada
Emend IVPowder, for solutionIntravenousMerck Ltd.2011-04-04Not applicableCanada
FosaprepitantPowder, for solution150 mgIntravenousApotex CorporationNot applicableNot applicableCanada
IvemendInjection, powder, for solution150 mgIntravenousMerck Sharp & Dohme B.V.2008-01-11Not applicableEu
IvemendInjection, powder, for solution150 mgIntravenousMerck Sharp & Dohme B.V.2008-01-11Not applicableEu
Additional Data Available
  • Application Number
    Application Number

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

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  • Product Code
    Product Code

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

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMylan Institutional LLC2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousNovadoz Pharmaceuticals Llc2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution115 mg/5mLIntravenousMylan Institutional LLC2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousBaxter Healthcare Corporation2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousApotex Corp2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousDr. Reddy's Laboratories Inc.,2019-09-06Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousFresenius Kabi USA, LLC2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousMsn Laboratories Private Limited2019-09-05Not applicableUs
FosaprepitantInjection, powder, lyophilized, for solution150 mg/5mLIntravenousBE Pharmaceuticals Inc.2019-09-05Not applicableUs
Additional Data Available
  • Application Number
    Application Number

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

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  • Product Code
    Product Code

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

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Categories
UNII
6L8OF9XRDC
CAS number
172673-20-0
Weight
Average: 614.4066
Monoisotopic: 614.116518403
Chemical Formula
C23H22F7N4O6P
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[C@@H](O[C@H]1OCCN(CC2=NC(=O)N(N2)P(O)(O)=O)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F

Pharmacology

Indication

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

Associated Conditions
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.

Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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
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
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Fosaprepitant.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Fosaprepitant.
3,5-diiodothyropropionic acidThe metabolism of Fosaprepitant can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Fosaprepitant.
5-androstenedioneThe metabolism of Fosaprepitant can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Fosaprepitant can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Fosaprepitant can be decreased when combined with 6-O-benzylguanine.
7-ethyl-10-hydroxycamptothecinThe metabolism of Fosaprepitant can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-aminocamptothecinThe metabolism of Fosaprepitant can be decreased when combined with 9-aminocamptothecin.
AbataceptThe metabolism of Fosaprepitant can be increased when combined with Abatacept.
Additional Data Available
  • Extended Description
    Extended Description

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

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  • Severity
    Severity

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

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  • Evidence Level
    Evidence Level

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

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  • Action
    Action

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Food Interactions
Not Available

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
External Links
Human Metabolome Database
HMDB0015662
KEGG Drug
D06597
PubChem Compound
219090
PubChem Substance
99443269
ChemSpider
189912
ChEBI
64321
ChEMBL
CHEMBL1199324
PharmGKB
PA165958390
Wikipedia
Fosaprepitant
AHFS Codes
  • 56:22.92 — Miscellaneous Antiemetics
  • 56:22.32 — Neurokinin-1 Receptor Antagonists

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingBasic ScienceTraumatic Brain Injury (TBI)1
1CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)2
1CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV) / Post-Operative Nausea and Vomiting (PONV)1
1TerminatedSupportive CareCancer, Breast / Nausea / Vomiting1
1TerminatedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
1, 2RecruitingTreatmentMultiple Myeloma (MM)1
1, 2TerminatedSupportive CareBreakthrough Nausea and Vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedPreventionCINV1
2CompletedSupportive CareColorectal Cancers / Nausea and vomiting1
2CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)2
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Nausea / Vomiting1
2RecruitingSupportive CareSarcomas1
2RecruitingTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
2TerminatedPreventionNausea / Vomiting1
2TerminatedSupportive CareNausea and vomiting / Stage III Squamous Cell Carcinoma of the Hypopharynx / Stage III Squamous Cell Carcinoma of the Larynx / Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage III Squamous Cell Carcinoma of the Nasopharynx / Stage III Squamous Cell Carcinoma of the Oropharynx / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IV Squamous Cell Carcinoma of the Oropharynx1
2TerminatedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
3Active Not RecruitingSupportive CareHematopoietic/Lymphoid Cancer / Nausea and vomiting / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)3
3CompletedSupportive CareGenital Neoplasms, Female / Nausea / Vomiting1
3CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV)1
3RecruitingSupportive CareNeoplasms, Malignant1
3TerminatedPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
4CompletedTreatmentCancer of the Ovary / Uterine Malignancies1
4RecruitingPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
4RecruitingPreventionNausea and Vomiting, Postoperative1
4RecruitingTreatmentPost-Operative Nausea and Vomiting (PONV)1
Not AvailableActive Not RecruitingSupportive CareChemotherapy-Induced Nausea and Vomiting (CINV) / Gastrointestinal Cancers1
Not AvailableCompletedTreatmentAdverse Effects of Medical Drugs / Chemotherapy-Induced Nausea and Vomiting (CINV) / Effects of Chemotherapy / Sarcomas1
Not AvailableUnknown StatusPreventionColorectal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous115 mg/5mL
Injection, powder, lyophilized, for solutionIntravenous150 mg/5mL
Powder, for solutionIntravenous
Powder, for solutionIntravenous150 mg
Injection, powder, for solutionIntravenous150 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5691336Yes1997-11-252019-09-04Us
Additional Data Available
  • Filed On
    Filed On

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

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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

Taxonomy

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
Phenylmorpholine / Trifluoromethylbenzene / Fluorobenzene / Halobenzene / Aralkylamine / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Azole
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines, triazoles, phosphoramide, (trifluoromethyl)benzenes, cyclic acetal (CHEBI:64321)

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 September 17, 2019 03:55