Xermelo
Carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy alone.
250 mg orally three times daily with food
Use in combination with a somatostatin analog
Dose reduction for hepatic impairment (Child-Pugh C): 250 mg once daily
Tablets: 250 mg (equivalent to 228.5 mg telotristat etiprate)
None listed.
- Constipation: In 6% (can be severe). Monitor and manage proactively. Reduce dose or D/C if severe constipation develops.
- Depression: In 3%. Monitor for depressed mood. Discontinue if depression worsens.
- Hepatic Enzyme Elevations: ALT/AST elevations reported. Monitor LFTs before and during treatment.
Nausea (13%), headache (11%), elevated GGT (9%), depression (9%), peripheral edema (7%), flatulence (6%), decreased appetite (7%), constipation (6%), abdominal pain (6%), pyrexia (5%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Telotristat ethyl is a prodrug hydrolyzed to the active metabolite telotristat (LP-778902), which inhibits tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis. NETs overexpress TPH and produce excess serotonin, causing carcinoid syndrome (diarrhea, flushing, bronchoconstriction). By inhibiting peripheral TPH (primarily TPH1 in enterochromaffin cells), telotristat reduces serotonin production and alleviates carcinoid syndrome diarrhea. It does not cross the blood-brain barrier significantly, minimizing effects on central serotonin.
Prodrug rapidly converted to active metabolite (telotristat). Telotristat Tmax: 0.5-2 hours. Half-life: approximately 5 hours (parent); 11 hours (active metabolite). Protein binding: >99%. Metabolized by carboxylesterases and CYP3A4. Excreted in feces (93%). Food increases exposure.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- TELESTAR — Telotristat ethyl vs. placebo for carcinoid syndrome diarrhea. Phase III, n=135.