Safety profile of olanzapine/samidorphan: focus on metabolic risks, opioid-related effects, and novel adverse events...

Olanzapine/samidorphan (O/S) represents an innovative therapeutic alternative for adult patients with schizophrenia and bipolar I disorder. However, most available safety data stems from clinical trials, limiting the ability to rapidly update emerging adverse events (AEs). O/S-related AEs, with a particular focus on metabolic diseases and novel signals (included opioid interference and psychiatric AEs), were systematically analyzed using the FDA Adverse Event Reporting System (FAERS) database in this study. Four disproportionality methods were utilized to assess the relationship between O/S and AEs from May 2021 (O/S first approved) to September 2024 using the FAERS database. Metabolic disease risk associated with O/S and olanzapine was compared using the reporting odds ratio method. A total of 2080 AE reports with O/S identified as the "primary suspect" were analyzed. Seventy-five preferred term signals and 23 system organ classifications were identified, predominantly within psychiatric disorders (19.37%). Nearly 20 novel potential AEs were identified. Although the overall risk of O/S-related metabolic diseases was lower than that of olanzapine (reporting odds ratio (ROR) [95% CI]: 3.55 [2.48-4.54] vs. 4.79 [4.51-5.08]), it still needs to be focused on. Notably, diabetic retinal edema and ketosis-prone diabetes mellitus presented the highest signal intensity for O/S and olanzapine, respectively. Psychiatric disorders, notably suicidal ideation, require vigilant monitoring in clinical settings. It is imperative to conduct traditional pharmacoepidemiological research to evaluate risk factors of O/S-related metabolic diseases in the future.