Objective To analyze adverse drug event (ADE) signals of subcutaneous pertuzumab-trastuzumab using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), and to provide evidence for safe clinical medication.

Methods ADE reports related to subcutaneous pertuzumab-trastuzumab submitted from the second quarter of 2020 to the third quarter of 2025 were extracted from the FAERS database. Signal detection was performed using three disproportionality analysis methods: the reporting odds ratio (ROR), the Medicines and Healthcare products Regulatory Agency's (MHRA) algorithm, and the Bayesian Confidence Propagation Neural Network (BCPNN).

Results A total of 3,707 ADE reports was identified with subcutaneous pertuzumab-trastuzumab as the primary suspected drug, involving 922 preferred terms. A total of 54 positive signals were detected by the ROR, MHRA, and BCPNN methods, involving 13 system organ classes (SOCs). The top six ADEs by signal strength were all related to the administration site. Diarrhea was the most frequently reported ADE, while general disorders and administration site conditions was the SOC with the highest number of signals and reports. Eleven signals, including acneiform dermatitis, decreased platelet count, subcutaneous hemorrhage, vulvovaginal dryness, and thermal burn, were not documented in the drug's prescribing information.

Conclusion Clinicians should monitor not only common ADEs but also potential signals (e.g., acneiform dermatitis, decreased platelet count) for early detection and early intervention.

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