rolapitant 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
neurokinin NK1 (substance P) receptor antagonist 5027 552292-08-7

Description:

MoleculeDescription

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:

DoseUnitRoute
0.18 g O

ADMET properties:

PropertyValueReference
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
BA (Bioavailability) 91 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.041 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 3.690 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 7.816 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 5.929 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.230 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.780 % High 1
herg hERG pIC50 5.181 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 2.877 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.355 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.440 % High 1
kinase-safety-class ACVR2B,BRAF,CAMK2D,CDK5,EIF2AK3,GRK2,MET,NTRK2,PDK1,PDK2,PDK4 11
kinase-selectivity-class AXL,EIF2AK3,PDK4 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 6.180 High 1
mh-clint Mouse hepatocyte intrinsic clearance 6.223 High 1
mppb Mouse plasma protein binding (% unbound) 0.340 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 33.343 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pppb Pig plasma protein binding (% unbound) 0.500 % High 1
rh-clint Rat hepatocyte intrinsic clearance 6.109 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 1.580 % High 1
rppb Rat plasma protein binding (% unbound) 0.380 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 28.774 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 1, 2015 FDA TESARO INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 114.17 57.30 53 442 456498 90171454
Flushing 103.68 57.30 32 463 88459 90539493
Infusion related reaction 66.85 57.30 36 459 416744 90211208
Dyspnoea 59.80 57.30 44 451 880911 89747041

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 133.33 55.61 60 195 471125 42149955
Flushing 57.57 55.61 17 238 37011 42584069

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Flushing 134.73 53.04 40 522 104696 110484041
Death 110.29 53.04 58 504 698811 109889926
Infusion related reaction 96.97 53.04 44 518 381118 110207619
Dyspnoea 62.19 53.04 48 514 1106824 109481913
Chest discomfort 56.61 53.04 24 538 173824 110414913

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A04AD14 ALIMENTARY TRACT AND METABOLISM
ANTIEMETICS AND ANTINAUSEANTS
ANTIEMETICS AND ANTINAUSEANTS
Other antiemetics
FDA MoA N0000010262 Neurokinin 1 Antagonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D064729 Neurokinin-1 Receptor Antagonists
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 antiemetic
CHEBI has role CHEBI:55350 neurokinin-1 receptor antagonist

Related Drugs by ATC class:

A04AD Other antiemetics 8 drugs
aprepitantcasopitantcerium oxalatechlorobutanoldronabinolmetopimazinenabilonescopolamine

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

DiseaseRelationSNOMED_IDDOID
Chemotherapy-induced nausea and vomiting indication 236084000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.44 acidic
pKa2 8.5 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent 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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Substance-P receptor GPCR ANTAGONIST Ki 9.18 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
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
NLE429IZUC INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Varubi HUMAN PRESCRIPTION DRUG LABEL 1 70720-101 TABLET 90 mg ORAL NDA 27 sections