Telotristat ethyl

Telotristat ethyl
Clinical data
Trade names Xermelo
Synonyms LX1032, LX1606
AHFS/Drugs.com Multum Consumer Information
Routes of
administration		 By mouth (tablets)
ATC code
  • None
Legal status
Legal status
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
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C38H46F4N6O9S
Molar mass 838.8696 g/mol
3D model (JSmol)

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 approved Xermelo 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]

Pharmacology

Telotristat is an inhibitor of tryptophan hydroxylase,[3] 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).[4]

Formulations

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

Telotristat etiprate

References

  1. 1 2 3 4 "Xermelo (telotristat ethyl) Tablets, for Oral Use. Full Prescribing Information" (PDF). Lexicon Pharmaceuticals, Inc. 8800 Technology Forest Place. The Woodlands, TX 77381. Retrieved 1 March 2017.
  2. ↑ "FDA Approves Xermelo for Carcinoid Syndrome Diarrhea". U.S. Food and Drug Administration. February 28, 2017. Retrieved 1 March 2017.
  3. ↑ Kulke, M; Hörsch, D; Caplin, M; Anthony, L; Bergsland, E; Oberg, K; Welin, S; Warner, R; Bohas, CL; Kunz, PL; Grande, E; Valle, JW; Lapuerta, P; Banks, P; Jackson, S; Jiang, W; Biran, T; Pavel, M (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.
  4. ↑ "FDA approves Xermelo for carcinoid syndrome diarrhea". FDA. Retrieved 15 March 2017.
  • Xermelo (telotristat ethyl) Official Web Site
  • Kulke, MH; O'Dorisio, T; Phan, A; Bergsland, E; Law, L; Banks, P; Freiman, J; Frazier, K; Jackson, J; Yao, JC; Kvols, L; Lapuerta, P; Zambrowicz, B; Fleming, D; Sands, A (October 2014). "Telotristat Etiprate, a Novel Serotonin Synthesis Inhibitor, in Patients with Carcinoid Syndrome and Diarrhea not Adequately Controlled by Octreotide". Endocrine-Related Cancer. 21 (5): 705–14. doi:10.1530/ERC-14-0173. PMC 4295770. PMID 25012985.
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