BackgroundTranexamic acid (TXA) is a widely used antifibrinolytic agent for the management of hemorrhagic disorders and has increasingly been investigated for the treatment of intracerebral hemorrhage (ICH). However, TXA-associated adverse drug events (ADEs), particularly neurological complications, remain insufficiently characterized, despite their association with unfavorable neurological outcomes, prolonged hospitalization, and increased in-hospital mortality. A systematic evaluation of TXA-related safety risks and underlying mechanisms in ICH is warranted.Materials and methodsFAERS reports from the first quarter of 2004 to the third quarter of 2023 were analyzed to identify TXA-associated ADE signals using a hierarchical prediction framework integrating statistical learning algorithms. Network toxicology analyses were conducted to explore potential molecular mechanisms and key regulatory targets involved in TXA-related effects in ICH. Drug–target interactions were further assessed by molecular docking and molecular dynamics simulations. In vitro experiments using ICH-related cell models were performed to validate the predicted neurotoxic effects of TXA.ResultsEight significant neurologically related ADE signals associated with TXA were identified, including myoclonic seizures and status epilepticus. Network toxicology analysis highlighted CASP3, PPARA, and BCL2 as key regulatory genes potentially mediating TXA-related neurotoxicity in ICH. Molecular docking demonstrated strong binding affinities between TXA and core targets, with binding energies lower than −8.0 kcal/mol. Molecular dynamics simulations confirmed stable binding conformations, with root mean square deviation values below 2.0 Å. In vitro experiments further supported the potential neurotoxic effects of TXA in ICH cell models.ConclusionThis study establishes an integrated computational-to-experimental framework for evaluating the safety of TXA in ICH. The FAERS analysis revealed overall neurological ADE signals for TXA. Combined with network toxicology and in vitro data, these findings suggest potential neurotoxic mechanisms that warrant cautious evaluation in future ICH-specific studies.