Abstract

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.

Highlights

  • Acute kidney injury (AKI) is a common and serious condition, with a prevalence of 15–60% among inpatients (Mehta et al, 2004; Hoste et al, 2015)

  • The number of VACV-related AKI events increased between June and September, and the same trend was observed for the percentage of AKI events

  • We demonstrated that many VACV-related AKI cases occur in summer in Japan

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Summary

Introduction

Acute kidney injury (AKI) is a common and serious condition, with a prevalence of 15–60% among inpatients (Mehta et al, 2004; Hoste et al, 2015). Valacyclovir (VACV), an antiviral prodrug of acyclovir (ACV), is effective against herpes zoster-associated pain and skin lesions (Colin et al, 2000; Lin et al, 2001). VACV is known as a common cause of drug-related AKI (Sugimoto et al, 2008; Roberts et al, 2011; Zhang et al, 2016). Drug-related acute kidney disease is a common side effect of valacyclovir (VACV) treatment. Analgesics are frequently administered concomitantly with VACV to treat the pain of herpes zoster, the differences between nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen in relation to VACV-related acute kidney injury (AKI) are unclear. We 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

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