Safety assessment of ambrisentan based on the FDA Adverse Event Reporting System

Ambrisentan is an endothelin receptor antagonist broadly used for the treatment of pulmonary arterial hypertension. However, multiple adverse events (AEs) were reported with its use, and we intended to evaluate potential ambrisentan-associated AE signals through the US Food and Drug Administration Adverse Event Reporting System. Reports from March 2019 to December 2022 were selected for disproportionality analysis. Four signal detection methods were applied, namely the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean, to assess ambrisentan-associated AE signals. Ambrisentan was identified as a suspected drug in 30,060 reports. AEs associated with ambrisentan covered 8 system organ classes and showed potential signals at the preferred-term level, such as peripheral edema and dyspnea, as well as cardiac AE signals including palpitations and cardiac failure. The median time to onset of ambrisentan-associated AEs was 240 days, and approximately half (49.66%) of the AEs with documented time to onset occurred after 1 year of use. Our research identifies potential safety signals of cardiac AEs associated with ambrisentan use. These signals are hypothesis-generating and warrant confirmation in prospective studies, as well as continued pharmacovigilance monitoring.