Safety profile of letrozole in the real world: a disproportionality analysis of FAERS database and systematic review of case reports.

Background: Letrozole is an aromatase inhibitor for breast cancer. Most of the safety data of letrozole came from clinical trials, while real-world information is insufficient.

Research design and methods: FAERS data were analyzed using OpenVigil 2 for disproportionality signals. A systematic review of PubMed, Embase, and CINAHL identified letrozole-related ADR case reports, evaluated by Naranjo Scale.

Results: The analysis of FAERS (2004 Q1-2023 Q4) identified 1,165 ADR signals from 29,631 cases, with general disorders, gastrointestinal, and musculoskeletal connective tissue disorders being the most frequent system organ classes (SOCs). Fatigue (3,431 cases), nausea (2,421), diarrhea (1,943), arthralgia (1,756), and alopecia (1,640) were the top reported signals. Novel signals included nitrituria and retinal phototoxicity, with 14 SOCs identified in the top 20 high-PRR signals. The systematic review included 45 cases from 40 publications, with skin/subcutaneous (13 cases) and musculoskeletal disorders (9 cases) most common. Notably, 26.67% of ADRs (12/45) were unreported in labeling, including rhabdomyolysis, systemic sclerosis, and acute kidney injury.

Conclusions: Clinicians need to pay attention to rhabdomyolysis when letrozole combined with catecholaminergic agents. Patient education on urine output monitoring is essential due to potential kidney injury. Bone marrow suppression and reproductive toxicity risks require clinical attention.