Safety evaluation of riociguat: insights from FAERS and VigiAccess databases, and establishment of pharmacist management framework

Abstract

A comprehensive understanding of the safety profile of riociguat is essential for optimizing patient management. We analyzed riociguat-associated adverse event (AE) reports from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) and VigiAccess databases. Gender-specific AEs, serious clinical outcomes, drug-drug interaction (DDI), and time-to-onset (TTO) analysis were evaluated. Findings were validated against clinical trials. Based on a narrative evidence review and pharmacovigilance findings, we proposed a pharmacist-led workflow. A total of 12,763 AE reports were identified in FAERS and 17,316 in VigiAccess, with females comprising the majority. The most frequently reported AEs were dyspnoea and hypotension. Strongest safety signals included diastolic hypotension and bendopnoea. After adjusting for age and body weight, females reported more dyspnoea, headache, nausea, vomiting, and chest pain. DDI analysis identified 30 interaction signals, primarily involving endothelin receptor antagonists (36.67%) and oral anticoagulants (33.33%). The median TTO was 225.0 days (IQR: 47.0–710.5 days). Pharmacovigilance findings demonstrated general concordance with safety data from six clinical trials. We established a pharmacist-led riociguat management workflow: pre-treatment evaluation, treatment initiation, and maintenance. Six core pharmacist responsibilities were identified: drug interaction management, safety signal recognition, patient education, efficacy and safety assessment, professional documentation, and quality indicators. This pharmacovigilance analysis confirmed known safety concerns with riociguat (hypotension, gastrointestinal disorders, peripheral edema), while identifying traumatic fractures and pain in jaw as additional safety signals. Gender differences and DDI signals warrant attention. These findings inform risk-benefit assessments and support the role of pharmacists in optimizing riociguat therapy management.