Risk of delirium with antiepileptic drug use: a study based on the Japanese Adverse Drug Event Report database.

BACKGROUND: Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. AIM: The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. METHOD: Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. RESULTS: There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. CONCLUSION: Our study's findings suggest that antiepileptic drug usage may be associated with delirium development.

Antihypertensive Drug Combinations Modify Cisplatin-induced Acute Kidney Injury.

BACKGROUND/AIM: There is limited evidence about the nephrotoxicity of calcium channel blockers (CCBs) and renin-angiotensin system (RAS) inhibitors with concomitant cisplatin (CDDP). We investigated whether combinations of antihypertensive drugs are associated with CDDP-related acute kidney injury (AKI) using the Japanese Adverse Drug Event Report database. PATIENTS AND METHODS: We analysed 544,864 reports in the database from 2004 to 2020. A reporting odds ratio (ROR) and confidence interval (CI) with adjustment for potential confounding factors was calculated for AKI for each drug and the combined use of the drugs and CDDP. RESULTS: CDDP, CCBs, and RAS inhibitors were all detected signals for AKI. The ROR in cases with concomitant use of CCBs, RAS inhibitors, and CDDP (adjusted ROR 7.28; 95% CI=5.56-9.54) was higher than that in cases with use of each drug. CONCLUSION: AKI may require more attention when patients receiving CDDP take CCBs and RAS inhibitors together.

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.