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.[3]
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| Trade names | Xermelo |
| Other names | LX1032, LX1606 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a617029 |
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| Routes of administration | By mouth |
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| 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%)[3] |
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| Formula | C27H26ClF3N6O3 |
| Molar mass | 574.99 g·mol−1 |
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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.[5][6] Telotristat ethyl was approved for use in the European Union in September 2017.[4]
The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7]
Pharmacology
editTelotristat is an inhibitor of tryptophan hydroxylase,[8] which mediates the rate-limiting step in serotonin biosynthesis.[3]
Adverse effects
editCommon 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).[5]
Formulations
editIt is marketed by Lexicon Pharmaceuticals (as telotristat etiprate). 328 mg telotristat etiprate is equivalent to 250 mg telotristate ethyl.[3]
References
edit- ^ "Summary Basis of Decision (SBD) for Xermelo". Health Canada. 23 October 2014. Retrieved 29 May 2022.
- ^ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada. 14 October 2020. Retrieved 17 April 2024.
- ^ a b c d e "Xermelo- telotristat ethyl tablet". DailyMed. 30 October 2020. Retrieved 11 November 2020.
- ^ a b "Xermelo EPAR". European Medicines Agency (EMA). 20 October 2017. Retrieved 17 April 2020.
- ^ a b "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.
- ^ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 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.
Further reading
edit- Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, et al. (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.
