Decoding Ambrisentan's Risks: A Deep Dive into FAERS Data

Abstract Objective This article aims to investigate the adverse drug event (ADE) signals associated with ambrisentan, a medication employed in the treatment of pulmonary arterial hypertension (PAH), and to offer guidance for its safe clinical application. Methods ADE reports related to ambrisentan were collected from the U.S. FDA Adverse Event Reporting System (FAERS) database between Q1 2007 and Q2 2024. Data mining was performed utilizing the Reporting Odds Ratio (ROR) method within disproportionality analysis. ADE names were standardized and coded according to the System Organ Class (SOC) and Preferred Term (PT) of the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Results A total of 45,007 ADE reports identified ambrisentan as the primary suspect drug. with 74.26% involving female patients, primarily aged 18–65. Notably, the majority of these reports, 85.75%, originated from the United States. The most common patient outcomes were hospitalization (46.19%). A total of 267 positive ADE signals were detected for ambrisentan. Notably, hematotoxicity related ADEs, such as decreased serum iron levels and iron-deficiency anemia, as well as nervous system-related ADEs, including exertional dizziness and syncope, were not documented in the drug's package insert. Additionally, other ADEs, such as elevated human chorionic gonadotropin (hCG) levels, atrial flutter, syncope, and jaw pain, were similarly omitted from the insert. The time-to-onset (TTO) analysis revealed that the majority of positive ADE signals were observed within the initial 0–30 days (9.05%) and beyond than 360 days (10.01%) following the commencement of treatment. Conclusion Our research had conducted a systematic summary of the adverse reactions of ambrisentan and explored the mechanism of its adverse reaction occurrence. We had verified the common adverse reactions of ambrisentan, including peripheral oedema, headache, nasal congestion, liver function impairment, and a strong signal for anemia. Additionally, we had discovered new positive signals of adverse reactions such as palpitations, atrial flutter, syncope, jaw pain, gastrointestinal bleeding, ear congestion, and middle ear effusion. This study provided a systematic elaboration on the adverse reactions of ambrisentan, emphasizing the importance of comprehensive monitoring and management of adverse reactions to ensure patient safety and optimize treatment outcomes.