Overview
11 DESCRIPTION Xermelo (telotristat ethyl) tablets contain telotristat ethyl as telotristat etiprate, a tryptophan hydroxylase inhibitor. Telotristat etiprate is the hippurate salt of telotristat ethyl [(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], which undergoes hydrolysis to the active metabolite,...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Telotristat, the active metabolite of telotristat ethyl, is an inhibitor of tryptophan hydroxylase, which mediates the rate limiting step in serotonin biosynthesis. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase is 29 times higher than that of telotristat ethyl. Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the gastrointestinal tract, and is over-produced in patients with carcinoid syndrome. Through inhibition of tryptophan hydroxylase, telotristat and telotristat ethyl reduce the production of peripheral serotonin, and the frequency of carcinoid syndrome diarrhea. 12.
Indications
- 1 INDICATIONS AND USAGE Xermelo is indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy. Xermelo is a tryptophan hydroxylase inhibitor indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy. ( 1 )
Common Doses
- 250 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of Xermelo in adult patients is 250 mg three times daily for patients whose diarrhea is inadequately controlled by SSA therapy. Administration Take Xermelo with food [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] . When short-acting octreotide is used in combination with Xermelo, administer short-acting octreotide at least 30 minutes after administering Xermelo [see Drug Interactions ( 7.3 )] . If a dose is missed, take the next dose at the regular time. Do not take 2 doses at the same time to make up for a missed dose.
Contraindications
- 4 CONTRAINDICATIONS Xermelo is contraindicated in patients with a history of a hypersensitivity reaction to telotristat. Reactions have included angioedema, rash and pruritis. History of hypersensitivity to telotristat. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions (≥5%) are nausea, headache, increased GGT, depression, flatulence, decreased appetite, peripheral edema, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TerSera Therapeutics LLC at 1-844-334-4035 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in...
Interactions
- 7 DRUG INTERACTIONS CYP3A4 Substrates (e.g., midazolam) and CYP2B6 Substrates (e.g., bupropion, efavirenz): Efficacy of concomitant drugs may be decreased; monitor patients’ response and consider increasing the dosage of the concomitant drug, if necessary. ( 7.1 ) 7.1 CYP3A4 Substrates Concomitant use of Xermelo may decrease the efficacy of drugs that are CYP3A4 substrates (e.g., midazolam) by decreasing their systemic exposure.