To detect safety signals and characterize the time-to-onset (TTO) profile of letermovir-associated adverse events (ADE) based on the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.

FAERS data from Q4 2017 to Q2 2025 were retrieved. Disproportionality analyses were performed using reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network. TTO was calculated and fitted using the Weibull distribution, with stratification by designated medical events (DME).

A total of 1 007 letermovir-related reports were identified, yielding 65 positive signals across 15 system organ classes. Among 778 cases with valid TTO, the overall median TTO was 43 (8, 124) days with a Weibull shape parameter β=0.58, indicating an early-onset pattern (cumulative proportion ≤30 days: 44.1%; ≤90 days: 66.8%). For key DMEs, liver failure exhibited typical early onset [median 5 (5, 5) days, β=0.88], whereas agranulocytosis [median 74 (40, 95) days, β=1.44] and acute kidney injury [median 88 (14, 579) days, β=0.68] demonstrated delayed and prolonged risk profiles.

Letermovir-associated ADE predominantly occurs early, but onset patterns vary across organ toxicities. Hepatic monitoring should be prioritized during early therapy, while hematologic and renal surveillance should be extended over a longer window.