Supplementary Material for: Postmarketing Safety of Temozolomide: A Pharmacovigilance Study Based on the FDA Adverse Event Reporting System

Abstract Background: Temozolomide is a widely used chemotherapy agent for the treatment of malignant gliomas and other brain tumors. Despite its established therapeutic benefits, there is an ongoing need to understand better its safety profile, particularly in real-world clinical settings. This study aimed to identify critical adverse drug reactions (ADRs) associated with Temozolomide by utilizing the FDA Adverse Event Reporting System (FAERS) database, thereby providing valuable safety insights for clinical practice. Methods: We utilized the reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). as primary algorithms for disproportionality analysis. Adverse events (AEs) were classified as adverse drug reactions (ADRs) only upon meeting the criteria set by all four algorithms. To ensure the accuracy of our results, we meticulously excluded any AEs deemed unrelated to Temozolomide. Results: From October 2003 to September 2023, a total of 10,502,538 case reports and 9073 cases explicitly attributed to Temozolomide were retrieved from the FAERS database. After applying our filters, 116 ADRs, each with a corresponding preferred term (PT), were identified across 18 system organ classes (SOCs). The identified ADRs associated with Temozolomide primarily involved bone marrow suppression, hepatotoxicity, and various infections, notably Pneumocystis jirovecii pneumonia. Furthermore, our analysis uncovered novel ADRs not previously documented in the drug label, including pulmonary embolism, etc. Conclusion: This real-world pharmacovigilance study has identified significant and previously unreported ADRs associated with Temozolomide. Further research for validation and resolution is urgently needed to guide the clinical application of Temozolomide, ensuring the safety and efficacy of its use in treating brain tumors.