Telotristat ethyl

Telotristat ethyl
Clinical data
Trade names	Xermelo
Other names	LX1032, LX1606
AHFS/Drugs.com	Multum Consumer Information
MedlinePlus	a617029
License data	US DailyMed: Telotristat_ethyl;
Routes of; administration	By mouth (tablets)
ATC code	A16AX15 (WHO) ;
Legal status
Legal status	US: ℞-only ;
Pharmacokinetic data
Protein binding	>99% (both telotristat ethyl and telotristat)
Metabolism	Hydrolysis via carboxylesterases
Metabolites	Telotristat
Elimination half-life	0.6 hours (telotristat ethyl), 5 hours (telotristat)
Excretion	Feces (92.8%), urine (less than 0.4%)[1]
Identifiers
	IUPAC name [(S)-Ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate];
CAS Number	1033805-22-9;
PubChem CID	25181577;
DrugBank	DB12095;
ChemSpider	28189674;
UNII	8G388563M7; 381V4FCV2Z;
KEGG	D09974;
ChEMBL	ChEMBL2105695;
Chemical and physical data
Formula	C27H26ClF3N6O3
Molar mass	574.99 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCOC(=O)C(CC1=CC=C(C=C1)C2=CC(=NC(=N2)N)OC(C3=C(C=C(C=C3)Cl)N4C=CC(=N4)C)C(F)(F)F)N;
	InChI InChI=1S/C27H26ClF3N6O3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35)/t20-,24+/m0/s1; Key:MDSQOJYHHZBZKA-GBXCKJPGSA-N;

Telotristat ethyl (USAN, brand name Xermelo) is a prodrug of telotristat, which is an inhibitor of tryptophan hydroxylase. It is formulated as telotristat etiprate — a hippurate salt of telotristat ethyl.[1]

On February 28, 2017, the U.S. Food and Drug Administration (FDA) approved telotristat ethyl in combination with somatostatin analog (SSA) therapy for the treatment of adults with diarrhea associated with carcinoid syndrome that SSA therapy alone has inadequately controlled.[2][3] Telotristat ethyl was approved for use in the European Union in September 2017.[4]

Pharmacology

Telotristat is an inhibitor of tryptophan hydroxylase,[5] which mediates the rate-limiting step in serotonin biosynthesis.[1]

Action of telotristat on tryptophan hydroxylase

Adverse effects

Common adverse effects noted in clinical trials include nausea, headache, elevated liver enzymes, depression, accumulation of fluid causing swelling (peripheral edema), flatulence, decreased appetite, and fever. Constipation is also common, and may be serious or life-threatening (especially in overdose).[2]

Formulations

It is marketed by Lexicon Pharmaceuticals (as telotristat etiprate). 328 mg telotristat etiprate is equivalent to 250 mg telotristate ethyl.[1]

Telotristat etiprate

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References

"Xermelo- telotristat ethyl tablet". DailyMed. 19 December 2019. Retrieved 17 April 2020.
"FDA Approves Xermelo for Carcinoid Syndrome Diarrhea" (Press release). U.S. Food and Drug Administration (FDA). February 28, 2017. Retrieved 1 March 2017.
"Xermelo (telotristat ethyl) Tablets". U.S. Food and Drug Administration (FDA). 4 April 2017. Retrieved 17 April 2020.
"Xermelo EPAR". European Medicines Agency (EMA). Retrieved 17 April 2020.
Kulke M, Hörsch D, Caplin M, Anthony L, Bergsland E, Oberg K, et al. (1 October 2016). "Integrated Placebo-Controlled Safety Analysis from Clinical Studies of Telotristat Ethyl for the Treatment of Carcinoid Syndrome". Annals of Oncology. 27 (6): 136–48. doi:10.1093/annonc/mdw369.07.

External links

"Telotristat ethyl". Drug Information Portal. U.S. National Library of Medicine.
"Telotristat etiprate". Drug Information Portal. U.S. National Library of Medicine.

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[PI-1] "Xermelo- telotristat ethyl tablet". DailyMed. 19 December 2019. Retrieved 17 April 2020.

[FDA_approval_PR-2] "FDA Approves Xermelo for Carcinoid Syndrome Diarrhea" (Press release). U.S. Food and Drug Administration (FDA). February 28, 2017. Retrieved 1 March 2017.

[3] "Xermelo (telotristat ethyl) Tablets". U.S. Food and Drug Administration (FDA). 4 April 2017. Retrieved 17 April 2020.

[4] "Xermelo EPAR". European Medicines Agency (EMA). Retrieved 17 April 2020.

[5] Kulke M, Hörsch D, Caplin M, Anthony L, Bergsland E, Oberg K, et al. (1 October 2016). "Integrated Placebo-Controlled Safety Analysis from Clinical Studies of Telotristat Ethyl for the Treatment of Carcinoid Syndrome". Annals of Oncology. 27 (6): 136–48. doi:10.1093/annonc/mdw369.07.