Risk of respiratory, thoracic, and mediastinal disorders associated with endothelin receptor antagonists and prostacyclin-related drugs in pulmonary hypertension: a disproportionality analysis based on FAERS

Expert Opin Drug Saf. 2024 Dec 3:1-12. doi: 10.1080/14740338.2024.2436077. Online ahead of print.

Abstract

Background: Adverse drug events (ADEs) for endothelin receptor antagonists (ERAs) and prostacyclin-related drugs (PRDs) have been reported in clinical trials, but large-scale, real-world evaluations for respiratory, thoracic, and mediastinal disorders (RTMD) remain scarce.

Methods: A pharmacovigilance analysis of the FAERS database (Q1 2004~Q2 2024) used the reporting odds ratio (ROR) method for disproportionality analysis to assess the adverse drug events (ADEs) of ERAs and PRDs in pulmonary arterial hypertension, focusing on risks related to RTMD.

Results: Reports of ADEs for ERAs (bosentan, ambrisentan, and macitentan) were 15,286, 36795, and 17,497, respectively, and for PRDs (epoprostenol, treprostinil, iloprost, and selexipag) were 5,477, 57265, 3,247, and 5,504. Females exceeded males, with most cases in adults. The top PTs for ERAs were death, dyspnea, and pneumonia, with bosentan linked to liver impairment. PRDs commonly cause headaches, flushing, hypotension, edema, and fluid retention. Dyspnea was the most reported RTMD risk for all drugs, and nasal congestion was noted for all. Selexipag had the fewest RTMD-related PTs, and iloprost had the strongest signal for hemoptysis.

Conclusion: The analysis highlights the RTMD risks of ERAs and PRDs in treating PH and underscores the need for careful monitoring of ADEs to ensure their safe and effective use in clinical practice.

Keywords: Endothelin receptor antagonists; FAERS; RTMD; adverse drug events; prostacyclin-related drugs; pulmonary hypertension.