Objective  Combining the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the network toxicology approach, to conducte a systematic analysis on the adverse drug events (ADE) related to octreotide and the potential toxic mechanisms, and provide a reference for clinical drug safety assessment.

Methods  All ADE reports data of octreotide was extracted from the FAERS database from the first quarter of 2004 to the second quarter of 2024. The signals mining was conducted using report odds ratio (ROR), proportion report ratio (PRR), and Bayesian credible interval neural network (BCPNN) methods. Evaluate its association with ADE, analyze the signal characteristics and distribution, and classify ADE signals using the preferred terms (PT) and system organ classification (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA) dictionary. Use network toxicology methods to analyze the key SOC selected, predict the potential targets of octreotide with PharmMapper and SwissTargetPrediction, obtain SOC-related targets from the GeneCards database, and conduct protein-protein interaction (PPI) network analysis with STRING. Perform GO function and KEGG pathway enrichment analysis in the DAVID database.

Results  A total of 21,430 adverse events involving octreotide as the primary suspected drug were retrieved. The signals affected 27 different SOC. After analyzing and processing the data, a total of 921 valid signals were obtained, mainly concentrated in systemic diseases and various reactions at the administration site (19.52%), gastrointestinal system diseases (12.25%), and various examinations (11.50%). Signals not mentioned in the instructions affected 16 different SOC. The analysis of the toxicological mechanisms of the 11 SOC involved in positive ADE signals revealed that the key targets included TP53, tumor necrosis factor (TNF), insulin (INS), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 (IGF-1), transforming growth factor β (TGF-β), SRC proto-oncogene (SRC), and the key pathways included TNF signaling pathway, TGF-β signaling pathway, puborectalis relaxin signaling pathway, estrogen signaling pathway.

Conclusion  The pharmacovigilance analysis identifies some new potential ADEs of octreotide. The network toxicology analysis indicates that the toxic effects of octreotide may be related to pathways such as the TNF signaling pathway, TGF-β signaling pathway, puborectalis hormone signaling pathway, and estrogen signaling pathway. A medication assessment should be conducted before administration, especially when patients have systemic diseases, gastrointestinal system diseases, neurological disorders, and other underlying diseases. It is recommended that during clinical use, relevant indicators should be monitored regularly, and attention should be paid to the reaction at the administration site. In case of adverse drug events or disease progression, relevant intervention measures should be taken promptly to ensure safe and rational drug use.

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