rolapitant 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
neurokinin NK1 (substance P) receptor antagonist	5027	552292-08-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: rolapitant rolapitant hydrochloride varubi SCH619734 SCH 619734	An orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life. Molecular weight: 500.49 Formula: C25H26F6N2O2 CLOGP: 4.71 LIPINSKI: 1 HAC: 4 HDO: 2 TPSA: 50.36 ALOGS: -5.48 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

rolapitant
rolapitant hydrochloride
varubi
SCH619734
SCH 619734

An orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life.

Molecular weight: 500.49
Formula: C25H26F6N2O2
CLOGP: 4.71
LIPINSKI: 1
HAC: 4
HDO: 2
TPSA: 50.36
ALOGS: -5.48
ROTB: 7

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.18	g	O

ADMET properties:

Property	Value	Reference
CL (Clearance)	0.38 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.00 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	148.50 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Sept. 1, 2015	FDA	TESARO INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Death	101.70	49.91	51	430	374330	63114211
Flushing	94.50	49.91	31	450	75056	63413485
Infusion related reaction	73.77	49.91	36	445	245485	63243056
Dyspnoea	56.01	49.91	43	438	661270	62827271
Acute interstitial pneumonitis	50.58	49.91	8	473	696	63487845

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Death	131.62	59.57	60	195	397989	34558687

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Flushing	125.87	53.22	39	502	88229	79655618
Infusion related reaction	106.16	53.22	44	497	230193	79513654
Death	100.49	53.22	56	485	566458	79177389
Dyspnoea	58.66	53.22	47	494	856978	78886869

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	A04AD14	ALIMENTARY TRACT AND METABOLISM ANTIEMETICS AND ANTINAUSEANTS ANTIEMETICS AND ANTINAUSEANTS Other antiemetics
FDA MoA	N0000010262	Neurokinin 1 Antagonists
MeSH PA	D064729	Neurokinin-1 Receptor Antagonists
MeSH PA	D018377	Neurotransmitter Agents
FDA EPC	N0000175786	Substance P/Neurokinin-1 Receptor Antagonist
FDA MoA	N0000182137	Cytochrome P450 2D6 Inhibitors
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
CHEBI has role	CHEBI:50919	antiemetico
CHEBI has role	CHEBI:55350	neurokinin-1 receptor antagonists

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Chemotherapy-induced nausea and vomiting	indication	236084000

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.44	acidic
pKa2	8.5	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 90MG BASE	VARUBI	TERSERA	N206500	Sept. 1, 2015	RX	TABLET	ORAL	7981905	April 4, 2027	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 90MG BASE	VARUBI	TERSERA	N206500	Sept. 1, 2015	RX	TABLET	ORAL	8404702	April 4, 2027	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 166.5MG BASE/92.5ML (EQ 1.8MG BASE/ML)	VARUBI	TERSERA	N208399	Oct. 25, 2017	DISCN	EMULSION	INTRAVENOUS	7981905	April 4, 2027	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 166.5MG BASE/92.5ML (EQ 1.8MG BASE/ML)	VARUBI	TERSERA	N208399	Oct. 25, 2017	DISCN	EMULSION	INTRAVENOUS	8404702	April 4, 2027	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 90MG BASE	VARUBI	TERSERA	N206500	Sept. 1, 2015	RX	TABLET	ORAL	7049320	Aug. 19, 2028	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 166.5MG BASE/92.5ML (EQ 1.8MG BASE/ML)	VARUBI	TERSERA	N208399	Oct. 25, 2017	DISCN	EMULSION	INTRAVENOUS	7049320	Aug. 19, 2028	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 90MG BASE	VARUBI	TERSERA	N206500	Sept. 1, 2015	RX	TABLET	ORAL	8470842	Jan. 18, 2029	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 166.5MG BASE/92.5ML (EQ 1.8MG BASE/ML)	VARUBI	TERSERA	N208399	Oct. 25, 2017	DISCN	EMULSION	INTRAVENOUS	8470842	Jan. 18, 2029	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY
EQ 166.5MG BASE/92.5ML (EQ 1.8MG BASE/ML)	VARUBI	TERSERA	N208399	Oct. 25, 2017	DISCN	EMULSION	INTRAVENOUS	9101615	July 14, 2032	PREVENTION OF DELAYED NAUSEA AND VOMITING ASSOCIATED WITH EMETOGENIC CANCER CHEMOTHERAPY

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Substance-P receptor	GPCR	P25103	NK1R_HUMAN	ANTAGONIST	Ki	9.18		SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
NLE429IZUC	UNII
D08988	KEGG_DRUG
914462-92-3	SECONDARY_CAS_RN
4034915	VANDF
C3273719	UMLSCUI
CHEBI:90908	CHEBI
CHEMBL3707331	ChEMBL_ID
10311306	PUBCHEM_CID
DB09291	DRUGBANK_ID
CHEMBL3707330	ChEMBL_ID
8882	INN_ID
C578834	MESH_SUPPLEMENTAL_RECORD_UI
5749	IUPHAR_LIGAND_ID
1665496	RXNORM
235787	MMSL
31164	MMSL
d08378	MMSL
016424	NDDF
016425	NDDF
715254008	SNOMEDCT_US
763538007	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Varubi	HUMAN PRESCRIPTION DRUG LABEL	1	70720-101	TABLET	90 mg	ORAL	NDA	27 sections