Akagi Tomoaki, Hamano Hirofumi, Miyamoto Hirotaka, Takeda Tatsuaki, Zamami Yoshito, Ohyama Kaname
Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
Department of Hospital Pharmacy, Okayama University Hospital, Okayama, Japan.
Eur J Clin Pharmacol. 2025 Jan;81(1):129-137. doi: 10.1007/s00228-024-03767-6. Epub 2024 Oct 23.
SN-38, the active metabolite of irinotecan, may cause adverse events necessitating treatment discontinuation and management. Diarrhea, which is treated with loperamide, is one such event. However, loperamide may delay SN-38 elimination, causing more adverse events. Therefore, understanding the adverse events caused by symptomatic drugs is crucial for safe drug therapy. This study aimed to assess the association between loperamide and irinotecan-induced adverse events.
We analyzed data up to December 2022 from VigiBase, the World Health Organization's adverse event database. The study used reporting odds ratios (RORs) to evaluate the associations between concomitant medications and irinotecan-induced adverse events. Fisher's exact probability test was used to analyze the adverse events. Logistic regression analysis was performed to identify associated adverse event signals.
Of the 32,520,983 cases analyzed, 57,454 involved the use of irinotecan. Among these, 1589 (2.8%) patients were co-treated with loperamide. Signals for neutropenia (ROR 1.37, 95% confidence interval (CI) 1.20-1.57, p < 0.001), anemia (ROR 1.81, 95% CI 1.43-2.30, p < 0.001), and alopecia (ROR 1.89, 95% CI 1.30-2.74, p < 0.01) were detected with concomitant loperamide. Multivariate logistic regression analysis confirmed that concomitant loperamide use was associated with signals for neutropenia, anemia, and alopecia.
Our results suggest that loperamide increases the risk of irinotecan-induced adverse events and enhances irinotecan toxicity. The study methodology may be useful for predicting adverse event risk when choosing symptomatic therapy drugs during irinotecan use.
伊立替康的活性代谢产物SN - 38可能引发不良事件，从而需要停药并进行处理。腹泻就是其中一种不良事件，常用洛哌丁胺进行治疗。然而，洛哌丁胺可能会延迟SN - 38的清除，进而引发更多不良事件。因此，了解对症治疗药物所导致的不良事件对于安全用药至关重要。本研究旨在评估洛哌丁胺与伊立替康所致不良事件之间的关联。
我们分析了世界卫生组织不良事件数据库VigiBase截至2022年12月的数据。该研究采用报告比值比（ROR）来评估联合用药与伊立替康所致不良事件之间的关联。采用Fisher精确概率检验分析不良事件。进行逻辑回归分析以识别相关的不良事件信号。
在分析的32520983例病例中，57454例使用了伊立替康。其中，1589例（2.8%）患者同时接受了洛哌丁胺治疗。发现同时使用洛哌丁胺会出现中性粒细胞减少（ROR 1.37，95%置信区间（CI）1.20 - 1.57，p < 0.001）、贫血（ROR 1.81，95% CI 1.43 - 2.30，p < 0.001）和脱发（ROR 1.89，95% CI 1.30 - 2.74，p < 0.01）的信号。多变量逻辑回归分析证实，同时使用洛哌丁胺与中性粒细胞减少、贫血和脱发的信号相关。
我们的结果表明，洛哌丁胺会增加伊立替康所致不良事件的风险并增强伊立替康的毒性。该研究方法可能有助于在使用伊立替康时选择对症治疗药物时预测不良事件风险。
