The study analyzed 7,843 adverse drug event (ADE) reports related to lumacaftor/ivacaftor (LUM/IVA) in the FAERS database from Q3 2015 to 2024 in cystic fibrosis patients with the F508del mutation. It identified 221 positive signals of safety risks, of which 37 agree with the drug label, 61 may be related to disease progression, and 123 are not listed on the label. The most frequent signals included infectious pulmonary exacerbations (n=1394, ROR 1201.58), hospitalization (n=841, ROR 20.07), and dyspnea (n=1025, ROR 50.37). Unexpected signals were depression (n=81, ROR 1.71), suicidal ideation (n=31, ROR 1.63) and hypoglycemia (n=20, ROR 2.02). Median time to onset of ADE was 256 days, with 39.2% of reports occurring after 360 days of treatment. Analyzes showed risk signals in subgroups according to age, weight, dosage and sex. The study emphasizes the need for long-term monitoring and updating of the drug label, especially for psychiatric symptoms.