Pharmacovigilance insights into drug-associated venous thromboembolism

Background: Venous thromboembolism (VTE), affecting 1-2 per 1,000 adults annually, represents a major preventable cause of hospitalization and mortality. The use of specific medications is an acquired risk factor for VTE. This pharmacovigilance study systematically evaluated medication-associated VTE risk using the largest publicly available adverse event database. Methods: Disproportionality analysis of adverse event reports from the US Food and Drug Administration Adverse Event Reporting System was conducted between 2004 Q1 and 2024 Q3. Medications were stratified by Anatomical Therapeutic Chemical classification, with time-to-event analysis using Weibull distribution modeling (shape parameter β). Results: There were 168,960 reports associated with drug-associated VTE, encompassing 1,718 medications. Of the 135 medications identified by disproportionality analysis as having a significant risk, 58 did not mention VTE in their package inserts. Antineoplastic and immunomodulating agents were found to have the largest number (64, 47.4%), followed by genito-urinary system and sex hormones (34, 25.2%), and blood and blood forming organs (16, 11.9%). The shape parameter β of all cases was 0.649 (95% CI: 0.643-0.656), indicating an early failure pattern. The shortest drug-associated times were observed with andexanet alfa, recombinant FVIIa, and basiliximab. Females (55%) and the 45-64 age group (34%) were predominantly affected. Reports and deaths due to drug-associated VTE have increased over the years. Conclusion: A total of 135 medications showed positive signals for VTE (58 unmentioned in package inserts). The high-risk profile of anti-tumor agents and immunomodulators was highlighted. These findings provide robust data-driven guidance for clinical pharmacotherapy to mitigate VTE risks.