Safety signals and CMV-related events reported during letermovir therapy: a FAERS database study

Background Letermovir is an antiviral agent approved for CMV infection prophylaxis in transplant recipients. This study aimed to evaluate safety signals reported during letermovir treatment, using data from the FDA Adverse Event Reporting System (FAERS). Methods Data from October 2017 to September 2024 were extracted from FAERS database. Reported events were analyzed across hierarchy levels, from Preferred Term (PT) to High-Level Terms (HLTs) and System Organ Classes (SOCs). Disproportionality analysis was performed to detect safety signals. Recorded time to onset was analyzed descriptively, and univariable logistic regression was performed to explore report-level factors. Results The most frequently reported events was infections and infestations at SOC level, cytomegalovirus infection at HLT level and CMV infection reactivation at Preferred Term level. Apart from CMV-related events, safety signals involved hematological abnormalities, pericardial effusion, hepatic and renal failure, bacterial and viral infections, pathogen resistance, and transplantation-related events. The median recorded time to onset was 25 days for all events, and 33 days for CMV-related events, with later recorded onset in intravenous than tablet reports. Exploratory logistic regression showed lower odds of CMV-related event reporting with older age and treatment initiation in more recent years, higher odds with intravenous administration, and regional differences in reporting. Conclusion This study identified safety signals reported with letermovir involving hematological, cardiac, hepatic, renal, infectious, and transplantation-related events. CMV-related signals may reflect breakthrough infection. These findings require validation in clinical studies.