Itraconazole Contaminated with Rilmazafone in Japan: A Retrospective Analysis Using the Japanese Adverse Drug Event Report Database.

backgroundIn early December 2020, the antifungal medication, itraconazole (ITCZ), was mistakenly contaminated with rilmazafone in Japan. Healthcare professionals reported adverse drug reaction reports associated with ITCZ and included central nervous system-depression symptoms such as dizziness, lightheadedness, loss of consciousness, and intense drowsiness.

objectiveWe examined ITCZ-associated suspicious cases using the Japanese Adverse Drug Event Report (JADER) database to determine the impact of adverse drug reaction reporting on post-marketing safety measures.

methodsAdverse drug reaction reports in which the suspicious or concomitant medication was ITCZ or fluconazole (FLCZ) were extracted from the JADER dataset. The number of adverse drug reaction reports associated with central nervous system-depression adverse drug reactions were counted, and chronological changes were compared with ITCZ and FLCZ.

resultsOf the 713,893 adverse drug reaction reports in the JADER database, 5048 cases were associated with ITCZ and 6007 cases with FLCZ. When ITCZ contamination occurred, the number of adverse drug reaction reports associated with ITCZ increased rapidly, while those with FLCZ did not. In addition, the proportion of central nervous system-depression adverse drug reactions increased only in the ITCZ-associated report.

conclusionsAn incident of ITCZ contamination with rilmazafone was detected on the JADER retrospectively. This case highlights the importance of spontaneous adverse drug reaction reporting, even if the causal relationship between the drug and adverse drug reaction is unknown.