Telotristat

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.

• 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.

• Xermelo is contraindicated in patients with a history of a hypersensitivity reaction to telotristat. Reactions have included angioedema, rash and pruritis.contraindicated

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. Discontinue Xermelo if severe constipation develops [see Warnings and Precautions ( 5.1 )]. The recommended dosage of Xermelo in adult patients is 250 mg three times daily for patients whose diarrhea is inadequately controlled by a SSA therapy. ( 2 ) Take Xermelo with food. ( 2 ) When short-acting octreotide is used in combination with Xermelo, administer short-acting octreotide at least 30 minutes after administering Xermelo. ( 2 , 7.3 ) Discontinue Xermelo if severe constipation develops. ( 2 , 5.1 )

Constipation: Xermelo reduces bowel movement frequency; monitor patients for constipation, and/or severe persistent or worsening abdominal pain. Discontinue Xermelo if constipation or abdominal pain develops. ( 5.1 ) 5.1 Constipation Xermelo reduces bowel movement frequency and may lead to constipation. Serious complications of constipation have been reported during clinical trials and postmarketing. In a 12-week, placebo-controlled trial, in which patients had 4 or greater bowel movements per day, 2 out of 45 patients treated with a higher than recommended dosage of Xermelo reported constipation. In one patient the constipation was serious, resulting in hospitalization. During the 36-week extension period with higher than the recommended dosage of Xermelo, 10 of 115 patients reported constipation, with individual reports of intestinal perforation, obstruction, and fecaloma. In another 12-week, placebo-controlled trial in which patients had less than 4 bowel movements per day, 4 out of 25 patients treated with the recommended dosage of Xermelo reported constipation. Serious complications of constipation in patients treated with Xermelo at the recommended dosage (e.g., intestinal obstruction) have also been reported in the postmarket setting. Most patients had additional risk factors, including underlying disease and concomitant constipating medications.

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 practice. Xermelo was studied in a double-blind, placebo-controlled clinical trial of 90 patients with metastatic neuroendocrine tumors and carcinoid syndrome diarrhea. Patients reported between 4 to 12 bowel movements daily despite the use of SSA therapy at a stable dose for at least 3 months [see Clinical Studies ( 14 )] . Placebo or Xermelo 250 mg was administered three times daily for 12 weeks. Concomitant anti-diarrheal medications (e.g., loperamide) were used by 43% (36% and 51% in the placebo and Xermelo group, respectively), pancreatic enzyme replacement medications by 39% (36% and 42% in the placebo and Xermelo group, respectively), and opioid analgesics by 29% (24% and 33% in the placebo and Xermelo group, respectively) of patients during the 12-week double-blind period of the trial. Table 1 below lists adverse reactions occurring at an incidence of at least 5% in the Xermelo group (N=45) and at an incidence greater than placebo (N=45) during the 12-week placebo-controlled period of the trial.

8.1 Pregnancy Risk Summary There are no human data with Xermelo use in pregnant women to inform a drug-associated risk. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of oral telotristat ethyl to rats during organogenesis at doses up to 750 mg/kg/day (approximately 9 times the exposure at the RHD [recommended human dose]). Treatment of pregnant rabbits with oral telotristat ethyl during organogenesis produced maternal toxicity and post-implantation loss at doses of 250 mg/kg/day or higher (approximately 15 times the exposure at the RHD), and reduced fetal weight at 500 mg/kg/day (approximately 33 times the exposure at the RHD). In a pre-/postnatal development study, an increased incidence of mortality in rat offspring was observed during postnatal days 0 to 4 at the maternal oral dose of 500 mg/kg/day (approximately 5 times the exposure at the RHD), given during organogenesis through lactation (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Absorption After a single oral dose of telotristat ethyl to healthy subjects, telotristat ethyl was absorbed and metabolized to its active metabolite, telotristat. Peak plasma concentrations of telotristat ethyl were achieved within 0.5 to 2 hours, and those of telotristat within 1 to 3 hours.

• Feb 28, 2017NDANDA208794Tersera

1. 1Diarrhoea83415%
2. 2Nausea62711%
3. 3Constipation60211%
4. 4Abdominal Pain5199.1%
5. 5Off Label Use5179.0%
6. 6Fatigue4157.3%
7. 7Flatulence3946.9%
8. 8Flushing3496.1%
9. 9Death3305.8%
10. 10Headache3265.7%
11. 11Drug Ineffective3205.6%
12. 12Malaise2554.5%
13. 13Hospitalisation2394.2%
14. 14Decreased Appetite2384.2%
15. 15Vomiting2043.6%

The 10 most recently updated of 27 ClinicalTrials.gov registrations naming Telotristat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor
  Active not recruiting · Phase 3 · Interventional · 79 enrolled · M.D. Anderson Cancer Center
  NCT04810091updated 2026-03-09
• Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer
  Completed · Phase 2 · Interventional · 23 enrolled · Emory University
  NCT03910387updated 2025-12-16
• AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With MetastaticNeuroendocrine Neoplasm
  Completed · Phase 2 · Interventional · 4 enrolled · Barbara Ann Karmanos Cancer Institute
  NCT03453489updated 2025-04-10
• Real-world Evidence Study EvaLuating PAtient-Reported Outcomes With XERMELO
  Completed · Observational · 223 enrolled · TerSera Therapeutics LLC
  NCT03223428updated 2024-07-24
• Telotristat With Lutathera in Neuroendocrine Tumors
  Terminated · Phase 2 · Interventional · 1 enrolled · Lowell Anthony, MD
  NCT04543955updated 2023-06-27
• A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer
  Terminated · Phase 2 · Interventional · 53 enrolled · TerSera Therapeutics LLC
  NCT03790111updated 2023-04-19
• Prospective Assessment of Patients With Neuroendocrine Tumors and Current or Prior History of Carcinoid Syndrome or Diarrhea Undergoing Peptide Receptor Radionuclide Therapy With or Without Telotristat Ethyl
  Withdrawn · Phase 2 · Interventional · 0 enrolled · Chandrikha Chandrasekhara
  NCT04713202updated 2023-02-10
• Telotristat Ethyl for Reducing Intraoperative Carcinoid Crisis in Patients With Neuroendocrine Tumors
  Withdrawn · Phase 2 · Interventional · 0 enrolled · University of Chicago
  NCT04672876updated 2021-12-17
• Retifanlimab (INCMGA00012) and Telotristat Ethyl for the Treatment of Advanced Neuroendocrine Tumors and Carcinoid Syndrome
  Withdrawn · Phase 2 · Interventional · 0 enrolled · M.D. Anderson Cancer Center
  NCT04776876updated 2021-09-29
• Open Label Study to Analyze the Effect of Telotristat Ethyl on Weight Regulation/Gain
  Withdrawn · Observational · 0 enrolled · Andrew Hendifar, MD
  NCT04034745updated 2020-12-30

Frequently asked questions

How does Telotristat work?

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.

What is Telotristat used for?

According to FDA labeling, Telotristat carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Telotristat?

Telotristat is classified as Various alimentary tract and metabolism products, Tryptophan Hydroxylase Inhibitor, Tryptophan Hydroxylase Inhibitors, Decreased Serotonin Production.

What are the contraindications for Telotristat?

Telotristat labeling lists contraindications including: Xermelo is contraindicated in patients with a history of a hypersensitivity reaction to telotristat. Reactions have included angioedema, rash and pruritis.. Always consult the full prescribing information and a clinician.