Objective  To analyze the adverse events (AEs) associated with tucatinib based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, the adverse events (AEs) associated with tucatinib, and to provide guidance for its safe clinical application.

Methods  AE reports listing tucatinib as the primary suspected drug from Q4 2020 to Q2 2025 were extracted from FAERS. AEs were coded using preferred terms (PT) and system organ class (SOC). Four disproportionality methods were employed for signal detection and analysis.

Results  A total of 2,968 AE reports associated with tucatinib were identified, predominantly from the United States (82.40%) and submitted by consumers (38.00%). Female patients accounted for as high as 89.10%, with the majority aged 60-74 years (21.30%). Most AEs occurred within 1 month of drug administration (45.52%, 178/391). After excluding irrelevant signals such as product issues and primary disease effects, statistical analysis was conducted on the positive results generated by the four algorithms, with a total of 82 PTs positive signals obtained, involving 15 SOCs. The common AEs listed in the tucatinib package insert, including diarrhea, nausea, palmar-plantar erythrodysesthesia, fatigue, and abnormal liver function, were generally consistent with the PTs and SOCs with high frequencies and signal intensities identified in this study. In addition,  a variety of AEs with strong signals that were not recorded in the package insert, such as onychalgia, onycholysis, memory impairment, cerebral edema, and abnormal examination results of reduced ejection fraction.

Conclusion  When using ticatinib in clinical practice, patients should be closely monitored for gastrointestinal disorders, liver and kidney function, skin conditions and neuropsychiatric symptoms. Cardiac function and electrolyte levels should be regularly assessed during treatment, and any abnormalities should prompt timely intervention and therapeutic adjustment.

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