Association Between Anticholinergic Drug Use and Febrile Neutropenia Induced by Anticancer Chemotherapy: Analysis of the Japanese Adverse Drug Event Report Database

Background/Aim: We previously reported that benzodiazepines with anticholinergic effects are a risk factor for infection in patients with diffuse large B-cell lymphoma; however, the effects of other anticholinergic drugs and the trend of severe infections, such as febrile neutropenia (FN), have not been investigated. The Japanese Anticholinergic Risk Scale (JARS) was developed by the Japanese Society of Geriatric Pharmacy to screen for potentially inappropriate medications with anticholinergic effects. This study aimed to elucidate the trend of FN induced by anticancer chemotherapy in patients who received anticholinergic drugs listed in the JARS. Patients and Methods: We obtained data from the JADER. Reporting odds ratios (RORs) were used to detect safety signals for FN. Anticholinergic drugs were classified into three categories according to their JARS score. Safety signals for FN were considered positive if the lower limit of the 95% confidence interval (CI) of the ROR was >1. Results: A total of 162, 918 cases were included in the dataset. RORs for FN indicated that cases with an anticholinergic risk score of 1 and 3 showed a safety signal (score 1: ROR=1.748, 95%CI=1.659-1.841; score 3: ROR=1.525, 95%CI=1.371-1.696), while no safety signals were observed for those with a risk score of 2 (ROR=1.015, 95%CI=0.863-1.194). Similar trends were observed in cases 70 years old and over and those under 70 years old. Conclusion: The trend of FN in patients who received an anticholinergic drug listed in the JARS was similar among younger and older patients.