S484 Adverse Event Profile of Telotristat in Carcinoid Syndrome Diarrhea: Insights From the FAERS Database

Introduction: Carcinoid syndrome (CS) diarrhea affects up to 80% of CS patients and poses a significant symptomatic and economic burden. These patients often experience diarrhea and flushing, leading to reduced quality of life and major lifestyle disruptions. Telotristat, a tryptophan hydroxylase inhibitor, was FDA approved in 2017 for CS diarrhea inadequately controlled by somatostatin analogs. Post-marketing data on its safety profile remain limited. In this study, we analyzed adverse drug reactions (ADRs) associated with telotristat using FDA Adverse Event Reporting System (FAERS) data to support informed, shared decision-making by prescribers and patients. Methods: This study utilized the FAERS to analyze adverse drug reactions (ADRs) potentially associated with telotristat use from January 2017 to December 2024. Data were extracted on patient demographics, reported ADRs, and outcomes. Descriptive statistics were used to analyze the ADR reports. Results: A total of 5,556 ADR reports were analyzed, including 375 deaths (6.7%) and 838 hospitalizations (15%). Gastrointestinal disorders were most common (47.6%), with diarrhea (14.1%) and constipation (10.5%) frequently reported. Intestinal obstruction occurred in 66 cases (5.7%), 42 (64%) of which were serious. Systemic effects included fatigue (384 cases, 6.9%) and facial or peripheral edema (252 cases, 4.5%). Neurological ADRs accounted for 12.3% of reports, primarily headache and dizziness. Psychiatric symptoms included depression (95 cases, 1.7%) and insomnia (77 cases, 1.4%). Cardiovascular ADRs were reported in 142 cases, with 43% considered serious. There were 452 infection-related ADRs (8.1%), with sepsis classified as serious in 78.6% of cases. Rare but notable events included visual disturbances (21 cases), angioedema/anaphylaxis (5 cases), and acute pancreatitis (4 cases). Conclusion: Telotristat is generally well tolerated; however, serious adverse events including cardiovascular (e.g., atrial arrhythmias), gastrointestinal (e.g., intestinal obstruction, severe constipation, pancreatitis), and neuropsychiatric effect can occur and add significant morbidity in chronically ill cancer patients. While causality and incidence cannot be established due to database limitations, recognizing potential ADRs is essential. As telotristat use increases for CS diarrhea, awareness among prescribers and patients is crucial for shared decision making and timely discontinuation if adverse effects emerge.