Identification
- Summary
Fosaprepitant is an antiemetic drug used in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting caused by chemotherapy.
- Brand Names
- Emend, Focinvez
- Generic Name
- Fosaprepitant
- DrugBank Accession Number
- DB06717
- Background
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
Structure for Fosaprepitant (DB06717)
- Weight
- Average: 614.4066
Monoisotopic: 614.116518403 - Chemical Formula
- C23H22F7N4O6P
- Synonyms
- Fosaprépitant
- Fosaprepitant
- Fosaprepitantum
- External IDs
- L-758,298
- L-758298
Pharmacology
- Indication
Fosaprepitant is indicated in adult and pediatric patients ≥6 months of age, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin.1 It is also indicated for the treatment of delayed nausea and vomiting with initial and repeat courses of moderately emetogenic cancer chemotherapy.1
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in prevention of Acute chemotherapy-induced nausea and vomiting (cinv) caused by highly emetogenic chemotherapy •••••••••••• •••••• ••••••••• ••••••••• Adjunct therapy in prevention of Delayed chemotherapy-induced nausea and vomiting (cinv) caused by highly emetogenic chemotherapy •••••••••••• •••••• ••••••••• ••••••••• Adjunct therapy in prevention of Delayed chemotherapy-induced nausea and vomiting (cinv) caused by moderately emetogenic chemotherapy •••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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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
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Fosaprepitant can be increased when it is combined with Abametapir. Abatacept The metabolism of Fosaprepitant can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Fosaprepitant. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Fosaprepitant. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Fosaprepitant. - 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Fosaprepitant dimeglumine D35FM8T64X 265121-04-8 VRQHBYGYXDWZDL-OOZCZQCLSA-N - Active Moieties
Name Kind UNII CAS InChI Key Aprepitant prodrug 1NF15YR6UY 170729-80-3 ATALOFNDEOCMKK-OITMNORJSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Emend Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous Merck Sharp & Dohme Limited 2010-11-12 Not applicable US 
Emend Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous Merck Sharp & Dohme LLC 2017-02-03 Not applicable US Emend Injection, powder, lyophilized, for solution 115 mg/5mL Intravenous Merck Sharp & Dohme Limited 2008-01-25 2012-07-31 US Emend IV Powder, for solution 150 mg / vial Intravenous Merck Ltd. 2011-04-04 Not applicable Canada 
Emend IV Powder, for solution 115 mg / vial Intravenous Merck Ltd. 2009-04-30 2010-10-28 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fosaprepitant Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous Accord Healthcare Inc. 2020-10-22 Not applicable US Fosaprepitant Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous BluePoint Laboratories 2019-11-20 Not applicable US Fosaprepitant Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous Northstar RxLLC 2023-01-28 Not applicable US Fosaprepitant Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous Novadoz Pharmaceuticals Llc 2019-09-05 Not applicable US Fosaprepitant Injection, powder, lyophilized, for solution 150 mg/5mL Intravenous Dr. Reddy's Laboratories Inc., 2020-07-01 Not applicable US
Categories
- Drug Categories
- Antiemetics
- Aprepitant and Prodrugs
- Autonomic Agents
- Central Nervous System Agents
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Gastrointestinal Agents
- Miscellaneous Antiemetics
- Morpholines
- Neurokinin 1 Antagonists
- Neurokinin-1 Receptor Antagonists
- Neurotransmitter Agents
- Oxazines
- Peripheral Nervous System Agents
- Substance P/Neurokinin-1 Receptor Antagonist
- 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)
- Affected organisms
- Not Available
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[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
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
- FDA Approved Drug Products: EMEND (fosaprepitant) for injection, for intravenous use [Link]
- External Links
- Human Metabolome Database
- HMDB0015662
- KEGG Drug
- D06597
- PubChem Compound
- 219090
- PubChem Substance
- 99443269
- ChemSpider
- 189912
- 1731071
- ChEBI
- 64321
- ChEMBL
- CHEMBL1199324
- ZINC
- ZINC000003939013
- PharmGKB
- PA165958390
- Wikipedia
- Fosaprepitant
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Prevention Chemotherapy-Induced Nausea and Vomiting 1 4 Completed Treatment Nausea, Postoperative 1 4 Completed Treatment Ovarian Cancer / Uterine Malignancies 1 4 Not Yet Recruiting Prevention Breast Cancer / Chemotherapy-Induced Nausea and Vomiting 1 4 Unknown Status Prevention Post Operative Nausea and Vomiting (PONV) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 150 mg Injection, powder, lyophilized, for solution Intravenous 115 mg/5mL Injection, powder, lyophilized, for solution Intravenous 150 mg/5mL Powder, for solution Intravenous 115 mg / vial Solution Intravenous 150.00 mg Injection, powder, lyophilized, for solution Intravenous 150.0 mg Injection Intravenous 150 mg/50mL Injection, solution Intravenous Injection, powder, lyophilized, for solution Intravenous 150 mg/1mL Injection, powder, lyophilized, for solution Intravenous 150 mg/1 Powder, for solution Intravenous 150 mg / vial Injection, powder, for solution Parenteral 150 mg Injection, solution, concentrate Intravenous 150 mg Injection, powder, for solution Intravenous 150 MG Solution Intravenous 245.300 mg Solution Intravenous 245.30 mg Injection Intramuscular 150 mg/150mg Injection, powder, for solution Intravenous 150 mg/1vial - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5691336 Yes 1997-11-25 2019-09-04 US US11065256 No 2021-07-20 2039-01-11 US US11065265 No 2021-07-20 2039-01-11 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00632 mg/mL ALOGPS logP 2.89 ALOGPS logP 2.47 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 1.05 Chemaxon pKa (Strongest Basic) 4 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 123.93 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 138.63 m3·mol-1 Chemaxon Polarizability 49.92 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.5225 Blood Brain Barrier - 0.81 Caco-2 permeable - 0.6534 P-glycoprotein substrate Substrate 0.8255 P-glycoprotein inhibitor I Non-inhibitor 0.6532 P-glycoprotein inhibitor II Non-inhibitor 0.986 Renal organic cation transporter Non-inhibitor 0.8583 CYP450 2C9 substrate Non-substrate 0.7018 CYP450 2D6 substrate Non-substrate 0.8588 CYP450 3A4 substrate Substrate 0.546 CYP450 1A2 substrate Non-inhibitor 0.7539 CYP450 2C9 inhibitor Non-inhibitor 0.644 CYP450 2D6 inhibitor Non-inhibitor 0.8521 CYP450 2C19 inhibitor Non-inhibitor 0.6705 CYP450 3A4 inhibitor Inhibitor 0.6258 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5 Ames test Non AMES toxic 0.5349 Carcinogenicity Non-carcinogens 0.7701 Biodegradation Not ready biodegradable 0.9899 Rat acute toxicity 2.6064 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5 hERG inhibition (predictor II) Inhibitor 0.6528
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 222.2293008 predictedDarkChem Lite v0.1.0 [M-H]- 212.59343 predictedDeepCCS 1.0 (2019) [M+H]+ 219.3647008 predictedDarkChem Lite v0.1.0 [M+H]+ 214.5334 predictedDeepCCS 1.0 (2019) [M+Na]+ 219.1093008 predictedDarkChem Lite v0.1.0 [M+Na]+ 220.27382 predictedDeepCCS 1.0 (2019)
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
References
- FDA Approved Drug Products: EMEND (aprepitant) oral capsules or suspension [Link]
- 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
- 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. [Article]
- FDA Approved Drug Products: EMEND (aprepitant) oral capsules or suspension [Link]
- Fosaprepitant FDA label [File]
Drug created at May 17, 2010 00:16 / Updated at February 20, 2024 23:55