Telotristat ethyl

Pregnancy
categoryRoutes of
administrationBy mouthATC codeLegal statusLegal status Pharmacokinetic dataProtein binding>99% (both telotristat ethyl and telotristat)MetabolismHydrolysis via carboxylesterasesMetabolitesTelotristatElimination half-life0.6 hours (telotristat ethyl), 5 hours (telotristat)ExcretionFeces (92.8%), urine (less than 0.4%)^[3]IdentifiersCAS NumberPubChem CIDDrugBankChemSpiderUNIIKEGGChEMBLChemical and physical dataFormulaC₂₇H₂₆ClF₃N₆O₃Molar mass574.99 g·mol⁻¹3D 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.^[3]

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

Telotristat is an inhibitor of tryptophan hydroxylase,^[8] which mediates the rate-limiting step in serotonin biosynthesis.^[3]

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).^[5]

Formulations

It is marketed by Lexicon Pharmaceuticals (as telotristat etiprate). 328 mg telotristat etiprate is equivalent to 250 mg telotristate ethyl.^[3]

References

Further reading

• 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.