A Comprehensive Disproportionality Analysis of Drug‐Related Head Injury Reports Using the FAERS Database

OBJECTIVE: This study aimed to identify and characterize drugs associated with reports of head injury through a comprehensive analysis of the FDA Adverse Event Reporting System (FAERS) database. METHODS: A retrospective disproportionality analysis was conducted on FAERS reports from 2004 to 2023. Cases were identified using a single Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term: "Head Injury" (PT code 10019196). Four disproportionality methods-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS)-were used to detect significant safety signals. RESULTS: Analysis of 26,485 head injury reports revealed a rising trend over time, with 84.12% being serious and 8.51% fatal. Strongest signals were detected for coagulation factors, notably vonicog alfa (ROR: 43.69) and pegylated factor VIII (ROR: 26.93). Chamomile also showed a significant association (ROR: 20.10). In contrast, warfarin had the highest report count (n = 429) but only a moderate signal strength (ROR: 6.77). CONCLUSION: This large-scale pharmacovigilance study identifies a strong association between coagulation factor therapies and reports of head injury. This signal most plausibly reflects confounding by indication rather than a direct prothrombotic mechanism. It also raises safety concerns regarding chamomile. These findings highlight the need for increased clinical vigilance and further investigation into these potential risks.