Tacrolimus Related Acute Pancreatitis: An Observational, Retrospective, Pharmacovigilance Study

Hui Yang; Zhuoling An; Yong Zhao; Hezhe Lu

doi:10.1016/j.clinthera.2024.04.005

Tacrolimus Related Acute Pancreatitis: An Observational, Retrospective, Pharmacovigilance Study

Clin Ther. 2024 May 9:S0149-2918(24)00083-3. doi: 10.1016/j.clinthera.2024.04.005. Online ahead of print.

Authors

Hui Yang¹, Zhuoling An², Yong Zhao³, Hezhe Lu⁴

Affiliations

¹ Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
² Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
³ Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen, China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁴ Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: hezhe@ioz.ac.cn.

PMID: 38729808
DOI: 10.1016/j.clinthera.2024.04.005

Abstract

Purpose: Recent case reports have drawn attention to the emergence of acute pancreatitis, a potentially life-threatening complication associated with tacrolimus. This study uses the Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate the risk signal of acute pancreatitis associated with calcineurin inhibitors (CNIs), with a focus on tacrolimus.

Methods: We conducted an observational retrospective pharmacovigilance study utilizing the FAERS database, encompassing data from its inception to the third quarter of 2023. The assessment of the association between CNIs and acute pancreatitis was carried out using the Information Component (IC) and Reporting Odds Ratio (ROR). Logistic regression analysis was employed to elucidate factors contributing to fatal outcomes. All analyses were performed using R version 3.2.5.

Finding: We identified 221 cases of acute pancreatitis linked to CNIs. The median age of individuals experiencing acute pancreatitis induced by tacrolimus was 43, with a predominant occurrence among male patients. Our study showed a significant association between CNIs and acute pancreatitis (ROR 1.82 [1.60-2.08], IC 0.85 [3.66-3.92]). Comparing tacrolimus and cyclosporine, the signal for tacrolimus seemed to be higher. Further analysis revealed that, with the exception of patients aged 60 and above, the signal for tacrolimus remained stable. Contrastingly, the signal for cyclosporine was unstable and limited to the male group and individuals aged less than 20 years. In cases of CNIs-related acute pancreatitis, the mortality rate was 31.67% (70/221 cases). Logistic regression analysis indicated that a younger age acts as a protective factor for death due to CNIs-related acute pancreatitis (OR 0.943, 95% CI 0.915-0.972, P = 0.000).

Implications: Our study has identified a safety signal for tacrolimus in relation to acute pancreatitis. Additionally, we observed advanced age as a significant risk factor for tacrolimus-related acute pancreatitis, leading to mortality. Given the widespread use of tacrolimus, it is crucial for healthcare providers to be vigilant and informed about the potential association with acute pancreatitis.

Keywords: Acute pancreatitis; Calcineurin inhibitors; Disproportionality analysis; Food and Drug Administration Adverse Events reporting system; Real-word study; Tacrolimus.