Rolapitant information

Rolapitant
Clinical data
Pronunciation	/roʊˈlæpɪtænt/ roh-LAP-i-tant
Trade names	Varubi (US), Varuby (EU)
Other names	SCH 619734
AHFS/Drugs.com	Monograph
MedlinePlus	a615041
License data	EU EMA: by INN; US DailyMed: Rolapitant;
Routes of; administration	By mouth (tablets), intravenous
Drug class	NK1 receptor antagonists, antiemetics
ATC code	A04AD14 (WHO) ;
Legal status
Legal status	US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	nearly 100%
Protein binding	99.8%
Metabolism	CYP3A4
Metabolites	C4-pyrrolidine-hydroxylated rolapitant (major)
Elimination half-life	169–183 hours
Excretion	Feces (52–89%), urine (9–20%)
Identifiers
	IUPAC name (5S,8S)-8-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl)- 8-phenyl-1,7-diazaspiro[4.5]decan-2-one;
CAS Number	552292-08-7 ;
PubChem CID	10311306;
IUPHAR/BPS	5749;
DrugBank	DB09291 ;
ChemSpider	8486772;
UNII	NLE429IZUC;
KEGG	D10742; as HCl: D08988;
ChEBI	CHEBI:90908 ;
CompTox Dashboard (EPA)	DTXSID90203740 ;
ECHA InfoCard	100.243.022
Chemical and physical data
Formula	C25H26F6N2O2
Molar mass	500.485 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES FC(F)(F)c(c4)cc(C(F)(F)F)cc4C(C)OCC3(c2ccccc2)NCC1(CC3)NC(=O)CC1;
	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; Key:FIVSJYGQAIEMOC-ZGNKEGEESA-N;

Rolapitant (INN,^[2] trade name Varubi /vəˈruːbi/ və-ROO-bee in the US and Varuby in the European Union) is a drug originally developed by Schering-Plough and licensed for clinical development by Tesaro, which acts as a selective NK₁ receptor antagonist (antagonist for the NK₁ receptor).^[3] It has been approved as a medication for the treatment of chemotherapy-induced nausea and vomiting (CINV) after clinical trials showed it to have similar or improved efficacy and some improvement in safety over existing drugs for this application.^[4]^[5]^[6]^[7]

^ ^a ^b "Varubi- rolapitant tablet". DailyMed. 6 August 2019. Retrieved 21 August 2020.
^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 59" (PDF). World Health Organization. p. 64. Retrieved 5 October 2016.
^ Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM (July 2012). "Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets". Pharmacology, Biochemistry, and Behavior. 102 (1): 95–100. doi:10.1016/j.pbb.2012.03.021. PMID 22497992. S2CID 24357198.
^ Jordan K, Jahn F, Aapro M (June 2015). "Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review". Annals of Oncology. 26 (6): 1081–90. doi:10.1093/annonc/mdv138. PMID 25755107.
^ Nasir SS, Schwartzberg LS (August 2016). "Recent Advances in Preventing Chemotherapy-Induced Nausea and Vomiting". Oncology. 30 (8): 750–62. PMID 27539626.
^ Rapoport B, Schwartzberg L, Chasen M, Powers D, Arora S, Navari R, Schnadig I (April 2016). "Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy". European Journal of Cancer. 57: 23–30. doi:10.1016/j.ejca.2015.12.023. PMID 26851398.
^ Chasen MR, Rapoport BL (March 2016). "Rolapitant for the treatment of chemotherapy-induced nausea and vomiting: a review of the clinical evidence". Future Oncology. 12 (6): 763–78. doi:10.2217/fon.16.11. PMID 26842387.

[Varubi_FDA_label-1] "Varubi- rolapitant tablet". DailyMed. 6 August 2019. Retrieved 21 August 2020.

[2] "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 59" (PDF). World Health Organization. p. 64. Retrieved 5 October 2016.

[3] Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM (July 2012). "Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets". Pharmacology, Biochemistry, and Behavior. 102 (1): 95–100. doi:10.1016/j.pbb.2012.03.021. PMID 22497992. S2CID 24357198.

[4] Jordan K, Jahn F, Aapro M (June 2015). "Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review". Annals of Oncology. 26 (6): 1081–90. doi:10.1093/annonc/mdv138. PMID 25755107.

[5] Nasir SS, Schwartzberg LS (August 2016). "Recent Advances in Preventing Chemotherapy-Induced Nausea and Vomiting". Oncology. 30 (8): 750–62. PMID 27539626.

[6] Rapoport B, Schwartzberg L, Chasen M, Powers D, Arora S, Navari R, Schnadig I (April 2016). "Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy". European Journal of Cancer. 57: 23–30. doi:10.1016/j.ejca.2015.12.023. PMID 26851398.

[7] Chasen MR, Rapoport BL (March 2016). "Rolapitant for the treatment of chemotherapy-induced nausea and vomiting: a review of the clinical evidence". Future Oncology. 12 (6): 763–78. doi:10.2217/fon.16.11. PMID 26842387.

Rolapitant information

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Rolapitant

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Substance P

Fezolinetant

ATC code A04

Fosaprepitant

Aprepitant

Elinzanetant

Tesaro

Casopitant

Netupitant

Tachykinin receptor 1

Neurokinin B

Talnetant

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Pharmaceutical industry in China

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Clinical data

Pronunciation	/roʊˈlæpɪtænt/ roh-LAP-i-tant
Trade names	Varubi (US), Varuby (EU)
Other names	SCH 619734
AHFS/Drugs.com	Monograph
MedlinePlus	a615041
License data	EU EMA: by INN US DailyMed: Rolapitant
Routes of administration	By mouth (tablets), intravenous
Drug class	NK1 receptor antagonists, antiemetics
ATC code	A04AD14 (WHO)
Legal status
Legal status	US: ℞-only^[1] EU: Rx-only
Pharmacokinetic data
Bioavailability	nearly 100%
Protein binding	99.8%
Metabolism	CYP3A4
Metabolites	C4-pyrrolidine-hydroxylated rolapitant (major)
Elimination half-life	169–183 hours
Excretion	Feces (52–89%), urine (9–20%)^[1]
Identifiers
IUPAC name (5S,8S)-8-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl)- 8-phenyl-1,7-diazaspiro[4.5]decan-2-one
CAS Number	552292-08-7^Y
PubChem CID	10311306
IUPHAR/BPS	5749
DrugBank	DB09291^Y
ChemSpider	8486772
UNII	NLE429IZUC
KEGG	D10742 as HCl: D08988
ChEBI	CHEBI:90908^Y
CompTox Dashboard (EPA)	DTXSID90203740
ECHA InfoCard	100.243.022
Chemical and physical data
Formula	C₂₅H₂₆F₆N₂O₂
Molar mass	500.485 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES FC(F)(F)c(c4)cc(C(F)(F)F)cc4C(C)OCC3(c2ccccc2)NCC1(CC3)NC(=O)CC1
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 Key:FIVSJYGQAIEMOC-ZGNKEGEESA-N