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.

Cutaneous adverse drug reaction (CADR) is a common problem in clinical medication. This study aimed to investigate the correlation between clinical drug application and CADR occurrence as evidence for preventive strategies and rational clinical drug use.
We analyzed the characteristics of CADRs of 858 patients admitted to Shandong Provincial Third Hospital from March 2007 to December 2018. The most significant drugs concerning the common skin symptoms and their significance to CADR were investigated by case-non-case and multiple logistic regression analyses.
A total of 266 drugs were involved in 858 cases of CADR. Among the ten most relevant medications, primarily antibiotics and herbal injections, and nutritional support drugs, potassium sodium dehydroandrographolide succinate injection, and cefoperazone sodium and sulbactam sodium injection were found to be 2.1 and 1.45 times statistically more prone to CADRs than to other adverse drug reactions (ADRs), respectively. The main route of administration was intravenous (63.16%), with oral administration accounting for 25.19%. There were 747 cases of ADR, 71 of severe ADR, 2 of new and severe ADRs, and 38 cases of new ADR. Overall, 100 cases of CADR exhibited abnormal alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels. The predictive factors for severe CADR occurrence included allergy and smoking histories, cefoperazone sodium, sulbactam sodium injection, levofloxacin lactate and sodium chloride injection.
Drug-induced CADR symptoms are commonly associated with other ARDs, predominantly rashes and pruritus, and are often accompanied by some medical conditions, especially liver and kidney damage. Detailed attention to a patient\'s primary diseases, allergy history, and drug safety profile could help prevent or reverse CADR in most patients.