Identification

Name

Rolapitant

Accession Number

DB09291

Description

Rolapitant is a potent, highly selective, long-acting Neurokinin-1 (NK-1) receptor antagonist approved for the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in adults. Delayed-phase CINV typically occurs >24 hours after chemotherapy treatment and is principally mediated by Neurokinin-1 and its ligand Substance P, which is released in the gut following chemotherapy administration. Neurokinin-1 is also known as Tachykinin Receptor 1 (TACR1), Neurokinin 1 Receptor (NK1R), and Substance P Receptor (SPR). By blocking Substance P from interacting with NK-1 receptors in the gut and the central nervous system, rolapitant prevents late-phase CINV. Unlike other available NK-1 receptor antagonists, rolapitant is not an inhibitor of Cytochrome P450 enzyme CYP3A4 and has a long elimination half-life, allowing a single dose to prevent both acute and late-phase CINV during the first 120 hours post-chemotherapy.

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Rolapitant (DB09291)

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Weight

Average: 500.485
Monoisotopic: 500.189847063

Chemical Formula

C₂₅H₂₆F₆N₂O₂

Synonyms

• Rolapitant

Pharmacology

Indication

This drug is indicated in adults in combination with other antiemetics for the prevention of delayed nausea and vomiting associated with emetogenic chemotherapy.

Associated Conditions

• Delayed chemotherapy induced naused and vomiting

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Not Available

Mechanism of action

Rolapitant is an orally active, highly selective Neurokinin-1 Receptor (NK1R) antagonist. NK1 receptors are located primarily in the gut and central nervous system and are activated by Substance P following chemotherapy administration. By binding to the NK1 receptor, rolapitant prevents binding of its ligand Substance P, which is released in the gut following chemotherapy administration.

Target	Actions	Organism
ANeurokinin 1 receptor	antagonist	Humans

Absorption

Following administration of rolapitant, plasma concentrations reached peak levels in about 4 hours.

Volume of distribution

460 L

Protein binding

Rolapitant is 99.8% bound to human plasma protein.

Metabolism

Rolapitant is metabolized primarily by Cytochrome P450 enzyme 3A4 (CYP3A4) to its major active and circulating metabolite M19 (C4-pyrrolidine-hydroxylated rolapitant).

Hover over products below to view reaction partners

• Rolapitant
  • M19 (C4-pyrrolidine-hydroxylated rolapitant)

Route of elimination

Rolapitant was found to be 14.2% renally excreted and 73% fecally excreted. Of the fecally excreted compounds

Half-life

Mean terminal half life ranged from 169 to 183 hours (~7 days).

Clearance

0.96 L/hour

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

Most common adverse reactions occurring in >3% of patients receiving moderately emetogenic chemotherapy and combinations of anthracycline and cyclophosphamide included decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis, and anemia. Most common adverse reactions occurring in patients receiving cisplatin-based highly emetogenic chemotherapy included neutropenia, hiccups, and abdominal pain.

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Unlock Additional Data
Abametapir	The serum concentration of Rolapitant can be increased when it is combined with Abametapir.
Abemaciclib	Rolapitant may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Acebutolol	The metabolism of Acebutolol can be decreased when combined with Rolapitant.
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Rolapitant.
Afatinib	The serum concentration of Afatinib can be increased when it is combined with Rolapitant.
Allopurinol	Rolapitant may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Almotriptan	The metabolism of Almotriptan can be decreased when combined with Rolapitant.
Alogliptin	The metabolism of Alogliptin can be decreased when combined with Rolapitant.
Alpelisib	The serum concentration of Alpelisib can be increased when it is combined with Rolapitant.
Ambrisentan	The serum concentration of Ambrisentan can be increased when it is combined with Rolapitant.

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

• Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of rolapitant.
• Take with or without food.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Rolapitant hydrochloride	J7Z9DBN8J0	858102-79-1	VEWAWEMXVUFANV-PVBCUUEWSA-N
Rolapitant hydrochloride monohydrate	57O5S1QSAQ	914462-92-3	GZQWMYVDLCUBQX-WVZIYJGPSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Varubi	Tablet	90 mg/1	Oral	Tersera Therapeutics Llc	2015-10-07	Not applicable
Varubi	Injection, emulsion	1.8 mg/1mL	Intravenous	Tesaro, Inc.	2017-10-25	Not applicable
Varubi	Tablet	90 mg/1	Oral	Tesaro, Inc.	2015-10-07	Not applicable

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

ATC Codes

A04AD14 — Rolapitant

• A04AD — Other antiemetics
• A04A — ANTIEMETICS AND ANTINAUSEANTS
• A04 — ANTIEMETICS AND ANTINAUSEANTS
• A — ALIMENTARY TRACT AND METABOLISM

Drug Categories

• Alimentary Tract and Metabolism
• Antiemetics and Antinauseants
• BCRP/ABCG2 Inhibitors
• Breast Cancer Resistance Protein Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors (moderate)
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Neurokinin 1 Antagonists
• Neurokinin-1 Receptor Antagonists
• Neurotransmitter Agents
• P-glycoprotein inhibitors
• Substance P/Neurokinin-1 Receptor Antagonist

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as delta amino acids and derivatives. These are compounds containing a carboxylic acid group and an amino group at the C5 carbon atom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Delta amino acids and derivatives

Alternative Parents

Phenylpiperidines / Trifluoromethylbenzenes / Azaspirodecane derivatives / Benzylethers / Aralkylamines / Pyrrolidine-2-ones / Secondary carboxylic acid amides / Lactams / Azacyclic compounds / Dialkylamines / Dialkyl ethers / Carbonyl compounds / Hydrocarbon derivatives / Organic oxides / Organofluorides / Organopnictogen compounds / Alkyl fluorides

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Substituents

2-pyrrolidone / Alkyl fluoride / Alkyl halide / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azaspirodecane / Benzenoid / Benzylether / Carbonyl group / Carboxamide group / Delta amino acid or derivatives / Dialkyl ether / Ether / Hydrocarbon derivative / Lactam / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organofluoride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phenylpiperidine / Piperidine / Pyrrolidine / Pyrrolidone / Secondary aliphatic amine / Secondary amine / Secondary carboxylic acid amide / Trifluoromethylbenzene

show 25 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Chemical Identifiers

UNII

NLE429IZUC

CAS number

552292-08-7

InChI Key

FIVSJYGQAIEMOC-ZGNKEGEESA-N

InChI

InChI=1S/C25H26F6N2O2/c1-16(17-11-19(24(26,27)28)13-20(12-17)25(29,30)31)35-15-23(18-5-3-2-4-6-18)10-9-22(14-32-23)8-7-21(34)33-22/h2-6,11-13,16,32H,7-10,14-15H2,1H3,(H,33,34)/t16-,22-,23-/m1/s1

IUPAC Name

(5S,8S)-8-{[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl}-8-phenyl-1,7-diazaspiro[4.5]decan-2-one

SMILES

C[C@@H](OC[C@]1(CC[C@]2(CCC(=O)N2)CN1)C1=CC=CC=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F

References

General References

1. Syed YY: Rolapitant: first global approval. Drugs. 2015 Nov;75(16):1941-5. doi: 10.1007/s40265-015-0485-8. [PubMed:26467681]
2. Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM: Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol Biochem Behav. 2012 Jul;102(1):95-100. doi: 10.1016/j.pbb.2012.03.021. Epub 2012 Mar 31. [PubMed:22497992]
3. Gan TJ, Gu J, Singla N, Chung F, Pearman MH, Bergese SD, Habib AS, Candiotti KA, Mo Y, Huyck S, Creed MR, Cantillon M: Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded, placebo-controlled randomized trial. Anesth Analg. 2011 Apr;112(4):804-12. doi: 10.1213/ANE.0b013e31820886c3. Epub 2011 Mar 8. [PubMed:21385988]

External Links

KEGG Drug

D10742

PubChem Compound

10311306

PubChem Substance

310265183

ChemSpider

8486772

RxNav

1665496

ChEBI

90908

ChEMBL

CHEMBL3707331

ZINC

ZINC000003816514

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Rolapitant

FDA label

Download (315 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Completed	Prevention	Chemotherapy-Induced Nausea and Vomiting (CINV)	3
2	Completed	Prevention	Nausea / Vomiting	1
2	Completed	Prevention	Post Operative Nausea and Vomiting (PONV)	1
2	Completed	Treatment	Coughing	1
2	Recruiting	Supportive Care	Chemo-radiation Induced Nausea and Vomiting	1
2	Terminated	Supportive Care	Locally Advanced Sarcoma	1
2	Withdrawn	Treatment	Germ Cell Tumors	1
1	Completed	Basic Science	Chemotherapy-Induced Nausea and Vomiting (CINV)	1
1	Completed	Prevention	Chemotherapy-Induced Nausea and Vomiting (CINV)	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, emulsion	Intravenous	1.8 mg/1mL
Tablet	Oral	90 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US8470842	No	2013-06-25	2029-01-18
US8404702	No	2013-03-26	2029-10-09
US8796299	No	2014-08-05	2022-12-17
US7049320	No	2006-05-23	2023-12-08
US7981905	No	2011-07-19	2027-04-04
US8361500	No	2013-01-29	2029-10-09
US7563801	No	2009-07-21	2027-04-04
US8178550	No	2012-05-15	2027-04-04
US9101615	No	2015-08-11	2032-07-14

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

Property	Value	Source
Water Solubility	0.00166 mg/mL	ALOGPS
logP	4.07	ALOGPS
logP	5	ChemAxon
logS	-5.5	ALOGPS
pKa (Strongest Acidic)	14.15	ChemAxon
pKa (Strongest Basic)	8.3	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	50.36 Å2	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	118.28 m3·mol-1	ChemAxon
Polarizability	46.18 Å3	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

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Drug created on October 29, 2015 15:22 / Updated on August 05, 2020 22:36