アブストラクト | PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
ジャーナル名 | European journal of clinical pharmacology |
Pubmed追加日 | 2024/10/24 |
投稿者 | Akagi, Tomoaki; Hamano, Hirofumi; Miyamoto, Hirotaka; Takeda, Tatsuaki; Zamami, Yoshito; Ohyama, Kaname |
組織名 | Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.;Department of Hospital Pharmacy, Okayama University Hospital, Okayama, Japan.;Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki;University, Nagasaki, Japan.;Department of Education and Research Center for Clinical Pharmacy, Faculty of;Pharmaceutical Sciences, Okayama University, Okayama, Japan.;zamami-y@okayama-u.ac.jp.;k-ohyama@nagasaki-u.ac.jp. |
Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/39443366/ |