Objective To mine adverse drug event (ADE) signals associated with lutetium [¹⁷⁷Lu] vipivotide tetraxetan based on the FDA Adverse Event Reporting System (FAERS) database and evaluate its safety profile in real-world settings.

Methods ADE reports related to lutetium [¹⁷⁷Lu] vipivotide tetraxetan were collected from the FAERS database from the first quarter of 2022 to the fourth quarter of 2025. Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were used for signal detection. The time-to-onset characteristics of ADEs were also analyzed.

Results A total of 11,396 ADE reports associated with lutetium [¹⁷⁷Lu] vipivotide tetraxetan were collected. A total of 33 positive signals were identified through signal mining, involving 11 system organ classes. The top 10 signals by number of reports were, in order: physical deterioration, death, laboratory test abnormality, anemia, platelet count decreased, thrombocytopenia, hemoglobin decreased, dry mouth, pancytopenia, and blood cell count decreased; the top 10 by signal strength were: physical deterioration, radiation exposure, haematology test abnormal, laboratory test abnormality, spinal infection, salivary hyposecretion, spinal cord compression, renal creatinine clearance decreased, radiation injury, and loss of libido. Eleven potential signals not mentioned in the drug label were newly identified, including general physical health deterioration, hematuria, loss of libido, subdural hematoma, hydronephrosis, decreased renal creatinine clearance, increased blood creatine, decreased performance status, failure to thrive, spinal infection, and urinary tract obstruction. Time-to-onset analysis showed a median time to ADE occurrence of 61 (28-124) days, with a Weibull distribution shape parameter β of 0.92 (0.86-0.98), indicating an "early failure" pattern and a risk that gradually decreases as treatment progresses.

Conclusion This study systematically characterizes the real-world adverse event profile of lutetium [¹⁷⁷Lu] vipivotide tetraxetan. In addition to known hematologic toxicities, new potential signals involving the renal and urinary system, nervous system, and psychiatric disorders were identified. ADEs predominantly occurred during the early treatment phase, suggesting that enhanced monitoring of hematologic and renal function should be strengthened during the early stage of treatment.

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