Macitentan adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2013 to 2024

This pharmacovigilance study analyzes the adverse event (AE) profile of Macitentan, a dual endothelin receptor antagonist used for pulmonary arterial hypertension (PAH), using real-world data from the FDA Adverse Event Reporting System (FAERS) from Q4 2013 to Q4 2024. Among 37,790 Macitentan-related AE reports, a high frequency of serious outcomes was observed, including hospitalization (41.9%) and death (22.3%). The most affected System Organ Classes (SOCs) were General Disorders, Respiratory, and Gastrointestinal Disorders. Disproportionality analysis identified both known AEs, such as fluid retention and anemia, and potential new safety signals not currently highlighted in the prescribing information, including left ventricular failure and abnormal brain natriuretic peptide levels. A sex-stratified analysis revealed distinct AE patterns, with males showing higher reporting of cardiopulmonary events and mortality, while females reported more breast cancer, autoimmune conditions, and urinary tract infections. Time-to-onset analysis indicated a bimodal distribution, with peaks in the first month of treatment and after one year, suggesting distinct early and late risk phases. These findings underscore the dynamic nature of Macitentan’s safety profile in real-world practice. The study highlights the need for individualized risk assessment, proactive monitoring—particularly for cardiac and sex-specific AEs—and reinforces the value of continuous post-marketing surveillance to optimize the safe use of Macitentan in PAH management.