Abstract:

Tacrolimus (Tac) is a cornerstone immunosuppressant in the treatment regimens for organ transplant recipients. However, its extensive clinical use has brought attention to its associated drug safety concerns. Recent case reports highlighting Tac-induced gastrointestinal ulcers have prompted further investigation. In the present study, we analyzed Tac-associated adverse events using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to identify potential adverse event signals. Adverse event reports were collected up to the third quarter (Q3) of 2023, revealing 339 cases of Tac-related gastrointestinal ulcers. A disproportionality analysis was conducted utilizing the Bayesian confidence propagation neural network of information component (IC) and reporting odds ratio (ROR) methods. All statistical analyses were performed using R version 3.6.1. The findings demonstrated a significant signal for gastrointestinal ulcers associated with Tac use, with a ROR₁ of 1.87 (95% CI: 1.68–2.08) and an IC₁ of 0.89 (95% CI: 0.73–1.05) when compared to all other drugs. When compared specifically to cyclosporine, Tac also showed a significant signal (ROR₂ = 1.55, 95% CI: 1.28–1.86; IC₂ = 0.24, 95% CI: 0.04–0.44). Further analysis identified age, male gender, and European descent as risk factors for mortality outcomes in patients with Tac-associated gastrointestinal ulcers. These findings highlighted the critical need for clinicians to strengthen the monitoring and early detection of gastrointestinal ulcers in patients undergoing Tac therapy. Enhanced vigilance in this regard is essential to optimize the management and care of transplant patients.

Key words: Tacrolimus, Gastrointestinal ulcers, Food and Drug Administration Adverse Events Reporting System, Disproportionality analysis, Real-word study