Risk Evaluation for Acute Kidney Injury Induced by the Concomitant Use of Valacyclovir, Analgesics, and Renin–Angiotensin System Inhibitors: The Detection of Signals of Drug–Drug Interactions

Background: Drug-related acute kidney disease is a common side effect of valacyclovir (VACV) treatment. Although analgesics are frequently administered concomitantly with VACV to treat the pain of herpes zoster, the differences between nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in relation to VACV-related acute kidney injury (AKI) are unclear. The risk for AKI with concomitant use of VACV and renin–angiotensin system (RAS) inhibitors that can cause AKI via a similar mechanism to NSAIDs is also unknown. We therefore evaluated the association between concomitant use of these drugs and VACV-related AKI, which was characterized according to the Japanese Adverse Drug Event Report (JADER) database. Methods: We analyzed data from the JADER database, which is a spontaneous reporting system. The reporting odds ratio was used to evaluate the signals of AKI. Results: A high proportion of VACV-related AKI cases occurred in summer. There was an increase in AKI signal in cases with concomitant use of VACV and NSAIDs, while no increase was detected in cases with concomitant use of VACV and acetaminophen. AKI events in cases with concomitant use of VACV and NSAIDs were more frequent in older and female patients and those with hypertension. Additionally, a signal increase for VACV-related AKI was observed with concomitant use of RAS inhibitors, with or without NSAIDs. Conclusions: We identified a seasonal variation in VACV-related AKI. Additionally, our findings indicate that acetaminophen might represent a safer analgesic than NSAIDs with respect to VACV-related AKI. We also identified candidate risk factors for AKI with concomitant use of NSAIDs, such as older age, female sex, and hypertension. Although further studies are warranted, our findings highlight the need to consider concomitant drug use and seasonal factors that lead to urinary output loss so that VACV-related AKI can be avoided.