Objective To identify the adverse drug event (ADE) signals of trofinetide based on the FDA Adverse Event Reporting System database, and to provide reference for clinical safe drug use.

Methods Trofinetide-related ADE reports from the first quarter of 2023 to the fourth quarter of 2025 were extracted from the FAERS database. Reports listing trofinetide as the primary suspected drug were screened. Signal detection was performed using four disproportionality analysis methods, followed by analyses of adverse event time-to-onset and age stratification.

Results A total of 5,314 ADE reports with trofinetide as the primary suspected drug were collected, and 98 positive signals were detected. Diarrhea and vomiting were the labelled ADEs with the highest reporting frequency. The top two signals with the highest reporting odds ratio values were diaper dermatitis and drooling. Time-to-onset analysis indicated that most ADEs occurred in the early stage of medication. Age-stratified analysis revealed highly consistent gastrointestinal risks between children aged 2~10 years and those aged 10~18 years, and cutaneous and infectious adverse events exhibited stronger association in younger patients.

Conclusion The most common ADEs associated with trofinetide are diarrhea and vomiting, consistent with clinical trial findings. Signals such as diaper dermatitis, drooling, and various infections are not clearly documented in the drug label and require further attention. Gastrointestinal reactions should be closely monitored during the early stage of treatment, and attention should be paid to cutaneous and infectious adverse events based on the age-stratified risk characteristics of children.

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