Telotristat

Class: Antidiarrhea Agents
- Tryptophan Hydroxylase Inhibitors
Chemical Name: Ethyl (S)-2-amino-3-[4-[2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl]phenyl]propanoate
Molecular Formula: C₂₇H₂₆ClF₃N₆O₃•C₉H₉NO₃
CAS Number: 1137608-69-5
Brands: Xermelo

Medically reviewed by Drugs.com on Nov 17, 2021. Written by ASHP.

Introduction

Tryptophan hydroxylase inhibitor.

Uses for Telotristat

Carcinoid Syndrome Diarrhea

Used (in combination with somatostatin analog therapy) for treatment of carcinoid syndrome diarrhea inadequately controlled by somatostatin analog therapy alone (designated an orphan drug by FDA for the treatment of carcinoid syndrome in patients with neuroendocrine tumors).

Carcinoid syndrome, a condition associated with serotonin overproduction, is characterized by flushing, diarrhea, wheezing, occasionally congestive heart failure, and various other manifestations. Although somatostatin analogs (e.g., octreotide, lanreotide) are standard treatment for carcinoid syndrome and are effective initially in most patients, some patients may not respond adequately or may develop recurrent symptoms, including diarrhea, despite therapy.

In clinical studies, telotristat ethyl reduced the frequency of daily bowel movements in patients with carcinoid syndrome diarrhea. Reductions in other symptoms of carcinoid syndrome (e.g., abdominal pain, flushing) not observed.

Telotristat Dosage and Administration

General

• Use in combination with a somatostatin analog (e.g., octreotide). (See Carcinoid Syndrome Diarrhea under Uses.)

• In the pivotal efficacy study, rescue therapy with short-acting octreotide and antidiarrheals (e.g., loperamide) was allowed and unrestricted.

• When used in combination with short-acting octreotide acetate, administer octreotide ≥30 minutes following administration of telotristat etiprate. (See Specific Drugs under Interactions.)

Restricted Distribution

• Available only through specialty pharmacies. Consult the Xermelo website for specific information ([Web]).

Administration

Oral Administration

Administer orally 3 times daily with food. (See Food under Pharmacokinetics.)

Dosage

Available as telotristat etiprate (the hippurate salt of telotristat ethyl); dosage expressed in terms of telotristat ethyl (the free base).

Adults

Carcinoid Syndrome Diarrhea

Oral

250 mg 3 times daily; use in combination with a somatostatin analog.

Higher dosages (e.g., 500 mg 3 times daily) have been studied in some patients, but increase the risk of adverse effects (e.g., severe constipation) without providing additional therapeutic benefit.

Therapy Interruption for Toxicity

GI Effects

If severe constipation or severe persistent or worsening abdominal pain occurs, discontinue therapy.

Prescribing Li