Abstract
BACKGROUND: Fondaparinux sodium, a synthetic pentose sugar, selectively inhibits factor Xa and is mainly used to prevent venous thromboembolism during major lower extremity orthopedic surgeries. It is also utilized for treating unstable angina pectoris and non-ST-segment-elevation myocardial infarction (NSTEMI). Given its extensive clinical application, comprehensive evaluation of its safety profile in clinical practice is essential. METHODS: This pharmacovigilance investigation systematically evaluated the post-marketing safety profile of fondaparinux sodium by leveraging real-world data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024), where fondaparinux sodium was the primary suspected drug. To further validate the robustness and generalizability of our findings, we cross-referenced the identified signals with data from two external sources: the VigiAccess database (Q2 2003 to Q4 2025) and the Japanese Adverse Drug Event Report (JADER) database (Q2 2007 to Q2 2025). Disproportionality analyses employed the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multiple empirical Bayes Gamma-Poisson shrinker (MGPS). Furthermore, sensitivity analyses were conducted to ensure the robustness of the results. Finally, the optimal parametric model was applied to estimate the temporal risk of adverse events (AEs). RESULTS: In the FAERS database, we identified 5,700 fondaparinux sodium-related AE reports, corresponding to 17,061 unique Preferred Terms (PTs). Time-to-onset analysis (N = 2,220) showed an early-peak profile (β = 1.2, median: 7 days), with 81.98% of events within 30 days. Disproportionality analysis confirmed positive signals for haemorrhagic complications across all demographics. Subgroup analysis revealed higher bleeding RORs in females, and increased risks of anemia and skin necrosis in the elderly patients(≥ 65 years). Pediatric patients (< 18 years) showed rare but significant hepatotoxicity. Healthcare professionals reported more complex clinical terms, while consumers reported more symptomatic events. Several unbalanced signals, including haematemesis (ROR = 14.52, 95%CI: 11.99-17.58) and skin necrosis (ROR = 27.29, 95%CI: 20.06-37.12) were identified. Sensitivity analyses further confirmed the robustness of these findings, and key signals were cross-referenced with the VigiAccess database and JADER database. The detection of these signals highlights potential safety concerns that warrant further clinical monitoring rather than confirming definitive causality. CONCLUSION: This study serves as a hypothesis-generating inquiry into the real-world safety of fondaparinux sodium. While our findings align with established adverse reaction profiles, they also highlight potential novel signals that warrant further investigation. These insights provide valuable reference points for clinical monitoring, particularly in special populations, though further epidemiological studies are needed to verify causality.