Abstract：
Fluoropyrimidines are anticancer drugs and can cause hyperammonemia both intravenously and orally. Renal dysfunction may interact with fluoropyrimidine to cause hyperammonemia. We performed quantitative analyses of hyperammonemia using a spontaneous report database to examine the frequency of intravenously and orally administered fluoropyrimidine, the reported frequency of fluoropyrimidine-related regimens, and fluoropyrimidine\'s interactions with chronic kidney disease (CKD).
This study used data collected between April 2004 and March 2020 from the Japanese Adverse Drug Event Report database. The reporting odds ratio (ROR) of hyperammonemia was calculated for each fluoropyrimidine drug and was adjusted for age and sex. Heatmaps depicting the use of anticancer agents in patients with hyperammonemia were drawn. The interactions between CKD and the fluoropyrimidines were also calculated. These analyses were performed using multiple logistic regression.
Hyperammonemia was observed in 861 of the 641,736 adverse events reports. Fluorouracil was the most frequent drug associated with hyperammonemia (389 cases). The ROR of hyperammonemia was 32.5 (95% CI 28.3-37.2) for intravenously administered fluorouracil, 4.7 (95% CI 3.3-6.6) for orally administered capecitabine, 1.9 (95% CI 0.87-4.3) for tegafur/uracil, and 2.2 (95% CI 1.5-3.2) for orally administered tegafur/gimeracil/oteracil. Calcium levofolinate, oxaliplatin, bevacizumab, and irinotecan were the most frequently reported agents in cases of hyperammonemia with intravenously administered fluorouracil. The coefficient of the interaction term between CKD and fluoropyrimidines was 1.12 (95% CI 1.09-1.16).
Hyperammonemia cases were more likely to be reported with intravenous fluorouracil than orally administered fluoropyrimidines. Fluoropyrimidines might interact with CKD in hyperammonemia cases.
This study used data collected between April 2004 and March 2020 from the Japanese Adverse Drug Event Report database. The reporting odds ratio (ROR) of hyperammonemia was calculated for each fluoropyrimidine drug and was adjusted for age and sex. Heatmaps depicting the use of anticancer agents in patients with hyperammonemia were drawn. The interactions between CKD and the fluoropyrimidines were also calculated. These analyses were performed using multiple logistic regression.
Hyperammonemia was observed in 861 of the 641,736 adverse events reports. Fluorouracil was the most frequent drug associated with hyperammonemia (389 cases). The ROR of hyperammonemia was 32.5 (95% CI 28.3-37.2) for intravenously administered fluorouracil, 4.7 (95% CI 3.3-6.6) for orally administered capecitabine, 1.9 (95% CI 0.87-4.3) for tegafur/uracil, and 2.2 (95% CI 1.5-3.2) for orally administered tegafur/gimeracil/oteracil. Calcium levofolinate, oxaliplatin, bevacizumab, and irinotecan were the most frequently reported agents in cases of hyperammonemia with intravenously administered fluorouracil. The coefficient of the interaction term between CKD and fluoropyrimidines was 1.12 (95% CI 1.09-1.16).
Hyperammonemia cases were more likely to be reported with intravenous fluorouracil than orally administered fluoropyrimidines. Fluoropyrimidines might interact with CKD in hyperammonemia cases.
摘要：
目的：氟嘧啶是抗癌药物，可通过静脉和口服引起高氨血症。肾功能障碍可能与氟嘧啶相互作用，导致高氨血症。我们使用自发报告数据库对高氨血症进行了定量分析，以检查静脉和口服氟嘧啶的频率，氟嘧啶相关方案的报告频率，和氟嘧啶与慢性肾脏病（CKD）的相互作用。
方法：本研究使用2004年4月至2020年3月从日本不良药物事件报告数据库收集的数据。计算每种氟嘧啶药物的高氨血症报告比值比（ROR），并根据年龄和性别进行调整。绘制了描述高氨血症患者使用抗癌剂的热图。还计算了CKD与氟嘧啶之间的相互作用。这些分析使用多元逻辑回归进行。
结果：在641,736份不良事件报告中的861份中观察到高氨血症。氟尿嘧啶是与高氨血症相关的最常见药物（389例）。静脉注射氟尿嘧啶的高氨血症的ROR为32.5（95％CI28.3-37.2），口服卡培他滨4.7（95%CI3.3-6.6），1.9（95%CI0.87-4.3）替加氟/尿嘧啶，和2.2（95％CI1.5-3.2）口服替加氟/吉马拉西/奥曲拉西。左亚叶酸钙，奥沙利铂,贝伐单抗,在静脉注射氟尿嘧啶的高氨血症病例中，伊立替康是最常见的药物。CKD与氟嘧啶相互作用项系数为1.12(95%CI1.09~1.16)。
结论：与口服氟尿嘧啶相比，静脉注射氟尿嘧啶更有可能报告高氨血症病例。在高氨血症病例中，氟嘧啶可能与CKD相互作用。
方法：本研究使用2004年4月至2020年3月从日本不良药物事件报告数据库收集的数据。计算每种氟嘧啶药物的高氨血症报告比值比（ROR），并根据年龄和性别进行调整。绘制了描述高氨血症患者使用抗癌剂的热图。还计算了CKD与氟嘧啶之间的相互作用。这些分析使用多元逻辑回归进行。
结果：在641,736份不良事件报告中的861份中观察到高氨血症。氟尿嘧啶是与高氨血症相关的最常见药物（389例）。静脉注射氟尿嘧啶的高氨血症的ROR为32.5（95％CI28.3-37.2），口服卡培他滨4.7（95%CI3.3-6.6），1.9（95%CI0.87-4.3）替加氟/尿嘧啶，和2.2（95％CI1.5-3.2）口服替加氟/吉马拉西/奥曲拉西。左亚叶酸钙，奥沙利铂,贝伐单抗,在静脉注射氟尿嘧啶的高氨血症病例中，伊立替康是最常见的药物。CKD与氟嘧啶相互作用项系数为1.12(95%CI1.09~1.16)。
结论：与口服氟尿嘧啶相比，静脉注射氟尿嘧啶更有可能报告高氨血症病例。在高氨血症病例中，氟嘧啶可能与CKD相互作用。
