To conduct data mining on tepotinib-associated adverse drug events (ADEs) using the US FDA Adverse Event Reporting System (FAERS) database, providing evidence for its clinical safety.

ADE reports for tepotinib from FAERS (Q1 2021 to Q4 2024) were analyzed. Signal detection methods included the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Multi-item Gamma Poisson Shrinker (MGPS). Sex-based differences in ADE signals were assessed using Fisher’s exact test with Bonferroni correction.

A total of 523 ADE reports identified tepotinib as the primary suspect drug, revealing 37 positive Preferred Terms (PT) across 14 System Organ Classes (SOCs). Notably, ADEs involving the ear and labyrinth disorders, infections and infestations, and nervous system disorders were not documented in the drug label. Several PTs—including malignant pleural effusion, infectious pleural effusion, central nervous system metastasis, pneumothorax, deafness, pericardial effusion, and dysgeusia—were newly identified as potential risks. Sex-stratified analysis showed higher diarrhea risk in women and a stronger appetite loss association in men. Importantly, interstitial lung disease (ILD) exhibited a significant signal in men (ROR=16.28, ROR025=8.71) but not in women, suggesting sex may be a key risk factor for tepotinib-induced ILD.

Clinicians should prioritize monitoring high-frequency, high-signal, and newly detected ADEs during tepotinib therapy. The drug label should be updated to include sex-specific ILD risk warnings.