Tryptophan hydroxylase inhibitor Pregnancy: No human data in pregnant women to inform a drug-associated risk. Animal data: no embryo-fetal effects in rats up to 750 mg/kg/day (approximately 9 times the exposure at the recommended human dose); in rabbits, maternal toxicity and post-implantation loss at 250 mg/kg/day or higher and reduced fetal weight at 500 mg/kg/day; increased offspring mortality on postnatal days 0 to 4 at a maternal dose of 500 mg/kg/day.

Telotristat ethyl

Brand names: Xermelo

Telotristat ethyl is an oral agent used in combination with somatostatin analogue therapy to treat carcinoid syndrome diarrhoea inadequately controlled by a somatostatin analogue alone.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 250 mg three times daily

Route: Oral — take with food

Frequency: Three times daily

US label (Xermelo) — no UK SPC was fetched. Indicated in adult patients whose carcinoid syndrome diarrhoea is inadequately controlled by somatostatin analogue (SSA) therapy. When short-acting octreotide is used in combination, administer the short-acting octreotide at least 30 minutes after telotristat ethyl. Missed dose: 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 if severe constipation develops — the drug reduces bowel movement frequency and serious complications of constipation (intestinal obstruction, perforation, faecaloma) have been reported. Paediatric: safety and effectiveness have not been established in paediatric patients. Geriatric: no overall differences in safety or effectiveness observed in patients 65 years and over, but greater sensitivity of some older individuals cannot be ruled out.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

History of a hypersensitivity reaction to telotristat (reactions have included angioedema, rash and pruritus)

Side effects

Nausea (most common, incidence 5% or greater)
Headache
Increased gamma-glutamyl transferase (GGT)
Depression
Flatulence and decreased appetite
Peripheral oedema and pyrexia; constipation (may be severe — discontinue if it develops)

Interactions

CYP3A4 substrates (e.g. midazolam) — efficacy may be decreased through reduced systemic exposure; monitor response and consider increasing the dose of the interacting drug
CYP2B6 substrates (e.g. bupropion, efavirenz) — efficacy may be decreased through reduced systemic exposure; monitor response and consider increasing the dose of the interacting drug
Short-acting octreotide — significantly decreases the systemic exposure of telotristat ethyl and its active metabolite telotristat; if needed, give short-acting octreotide at least 30 minutes after telotristat ethyl

Clinical monograph

How it works

Its active metabolite inhibits tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, reducing peripheral serotonin production that drives carcinoid-related diarrhoea.

Prescribing in practice

Because reducing serotonin can affect mood, depression and reduced mood have been reported, and patients should be monitored for and advised to report such symptoms.
Gastrointestinal effects including nausea and abdominal pain are common, and constipation can occur as diarrhoea improves.
Liver enzyme elevations have been observed, so hepatic function should be considered during treatment.

Monitoring

Monitor stool frequency and clinical response, together with mood and liver function, during treatment.

Counselling the patient

Take the medicine with food as directed and continue your somatostatin analogue treatment.
Report low mood or depression to your clinical team.
Tell your team if constipation or persistent abdominal pain develops.

Evidence & guidelines

The TELESTAR trial demonstrated reduced bowel movement frequency in carcinoid syndrome diarrhoea, consistent with the SPC and NICE appraisal.

Reference: NICE TA487; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways