Telotristat Ethyl: A Review in Carcinoid Syndrome Diarrhoea
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Telotristat ethyl (Xermelo®), a first-in-class peripheral tryptophan hydroxylase (TPH) inhibitor, is approved to treat carcinoid syndrome diarrhoea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy alone. Some neuroendocrine tumours secrete serotonin (5-HT) into the blood, resulting in frequent bowel movements (BMs) and other symptoms. Telotristat ethyl inhibits TPH, thereby reducing the production of 5-HT and improving carcinoid syndrome diarrhoea. In the 12-week placebo-controlled phase of randomized trials in patients with carcinoid syndrome diarrhoea (most of whom were receiving SSA therapy), the addition of oral telotristat ethyl 250 three times daily provided significant reductions in the frequency of BMs and levels of urinary 5-hydroxyindolacetic acid (u5-HIAA; a metabolite of 5-HT) relative to placebo. Telotristat ethyl 250 mg three times daily was well tolerated, with the proportion of patients reporting at least one treatment-emergent adverse event being similar to that with placebo. With regard to adverse events of special interest, relative to placebo, telotristat ethyl had a comparable incidence of depression-related symptoms, a somewhat higher incidence of gastrointestinal (GI) disorders and a higher incidence of elevated hepatic enzyme levels.
During the peer review process, the manufacturer of telotristat ethyl was also offered the opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflicts of interest
Katherine A. Lyseng-Williamson is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
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