Real-world study of adverse events associated with selumetinib based on the VigiAccess and FAERS databases

Background Selumetinib is the first drug approved for the treatment of neurofibromatosis type 1 (NF1). This study aims to evaluate the safety profile of selumetinib in real-world clinical settings. Methods Data on adverse events (AEs) associated with selumetinib was retrieved from the WHO-VigiAccess and FAERS databases, covering the period from their respective inception to 31 October 2024. AEs were classified based on the relevant system organ classes (SOCs) and preferred terms (PTs) from the Medical Dictionary for Regulatory Activities (MedDRA), signal detection was performed using the reporting odds ratio (ROR) method. Results A total of 1,313 reports from WHO-VigiAccess and 714 from FAERS related to selumetinib were analyzed. AEs spanned 27 SOCs, with similar distribution observed in both databases. Among the top 30 PTs, several, including increased blood lactate dehydrogenase, retinal detachment, and pneumonia, were not in the label. In FAERS, 70 positive signals across 16 SOCs were detected, with 26 PTs not in the insert, and 18 classified as important medical events (IMEs). The three PTs with the highest signal intensity were serous retinopathy, nail bed infection, and paronychia. Unexpected AEs, such as hyperphosphatemia, mitral valve incompetence, personality change, and streptococcal pharyngitis, were identified. The median time to onset of AEs was 26 days (interquartile range [IQR], 6–79 days). Conclusion This study provides valuable insights into potential novel AEs, contributing to ongoing efforts to ensure the safety of the drug post-marketing and aiding in the management of clinical risks.