Recently, there have been reports that the combination of renin angiotensin inhibitors, diuretics, and non-steroidal anti-in‰ammatory drugs increases the risk of acute kidney injury (AKI). This combination has been dubbed the``Triple Whammy''. However, there have been no reports about its chronic eŠects on the kidney. In this study, we investigated the chronic eŠects of the``Triple Whammy'' on kidney function. There were 203 outpatients who were prescribed this combination in our hospital for 5 years. We excluded patients who could also conˆrm the combination in the previous year and patients for whom laboratory data were unavailable, thus, leaving a target patient group of 95 patients. The average estimated glomerularˆltration rate (eGFR) decreased signiˆcantly from 62.6 to 58.9 mL/min/1.73 m 2 immediately after administering the combination (p ＜ 0.01). Although no patients were diagnosed with AKI within 90 days after being administered the combination, 7.4％ of patients exhibited a  25％ reduction in eGFR compared with that before commencing the combination. Correlation analysis of gender, age, past renal function, and renal function change demonstrated that eGFR before administration of the combination negatively correlated with changes in eGFR (p ＜ 0.01). Considering the eŠects of individual diŠerences, eGFR changes before and after administering the combination were compared using a case-crossover design and eGFR after administering the combination was found to be signiˆcantly reduced (p ＜ 0.01). Therefore, it appears that the``Triple Whammy'' may cause not only AKI but also chronic renal degeneration.

Acute kidney injury (AKI) associated with “Triple Whammy” drug therapy consisting of renin-angiotensin system inhibitors, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported. There have been no reports investigating “Triple Whammy” drug therapy and the time to AKI onset using adverse drug events report databases. The aim of this study was to determine the relationship between the time to AKI onset and treatment with “Triple Whammy” drug therapy. We analyzed AKI cases registered in the Japanese Adverse Drug Event Report database. The data were analyzed using the Kaplan–Meier approach, generalized Wilcoxon tests, and Weibull distribution. AKI was reported in 18,415 cases, of which 7,466 cases used Triple Whammy drugs. All combinations of Triple Whammy drugs were associated with significantly higher odds ratios for reporting AKI. In Weibull analysis, AKI onset was early for most combination patterns of Triple Whammy drugs. The Kaplan–Meier approach showed that the treatment duration to AKI onset was much shorter in cases using NSAIDs; median onsets, 8 days for triple combination, 7 days for NSAIDs added to renin-angiotensin system inhibitors, 9 days for NSAIDs added to diuretics, 6 days for diuretics added to NSAIDs, and 9 days for NSAIDs alone. AKI associated with Triple Whammy drugs is likely to occur in the early stages of treatment, especially with concomitant NSAIDs. Patients should be monitored for the occurrence of AKI within the first 2 weeks.

The proper use of drugs with renal excretion and nephrotoxicity is an urgent problem due to the increase in CKD patients. We have been sharing renal function data on CKD patients among medical staff, including community pharmacists, using the CKD sticker since March, 2012 in Shiga. The CKD sticker is affixed to the medication log book of CKD patients. We performed questionnaire surveys of all community pharmacies in Shiga for five years from 2012 to 2016, and examined the utility of the CKD sticker. The CKD sticker was recognized at 98.6％ of pharmacies in 2016. Pharmacies attended by patients with the CKD sticker increased to 68.8％ in 2016. In addition, there were no local differences among 9 branches in the Shiga Pharmacist Society in 2016. The number of pharmacies that performed questionable inquiries based on the CKD sticker increased from 7.7％ in 2012 to 24.7％ in 2016. Pharmacies that inquired about patients with CKD stickers greatly increased in 2016, and the number of prescription changes increased. The spread of CKD stickers was observed throughout the prefecture, and this study demonstrated that the CKD sticker was a useful tool for questionable inquiries. The CKD sticker helped to avoid the use of drugs in cases with nephrotoxicity and to reduce the quantity of drugs in cases with renal excretion, allowing for safe medication of CKD patients.

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In clinical practice, edoxaban is sometimes prescribed for off-label use based on the hypothesis that it is as safe and effective as warfarin. However, there is limited safety information on off-label use due to lack of clinical trial. We aimed to analyze the tolerability of off-label use of edoxaban and to identify patient characteristics associated with major bleeding as adverse effects. Patients under edoxaban treatment between January 2017 and December 2017 were enrolled in this retrospective cohort study. The incidence of major bleeding with off-label use compared with on-label use was analyzed using by log-rank test. Univariate and multivariate regression analysis were undertaken to detect independent variables with significant odds ratio that associated with major bleeding. After the exclusion criteria were applied, the patients were divided into two groups: off-label group (n = 30) and on-label group (n = 161). Incidence of major bleeding was found to be higher in the off-label group (13.3%) than in the on-label group (3.7%) (p<0.05). Multivariate adjustment showed that the off-label use or portal vein thrombosis and patients with history of major bleeding has significantly higher incidence of major bleeding. We demonstrated that off-label use of edoxaban may be a significant risk factor for major bleeding.