Shingo Kondo

“Triple whammy” prescriptions, combining non-steroidal anti-inflammatory drugs (NSAIDs), renin–angiotensin system (RAS) inhibitors, and diuretics, increase acute kidney injury (AKI) risk. To clarify the frequency and profiles of these prescriptions and identify vulnerable populations, we analyzed the AHI partners database to estimate the number of individuals prescribed these three drug classes. In the single-agent analysis, loxoprofen was the most commonly prescribed NSAID (66.3%), olmesartan (19.4%) and telmisartan (15.9%) were the predominant RAS inhibitors, and furosemide (19.6%) and spironolactone (16.0%) were the most frequently used diuretics. Dual-drug combinations showed patterns consistent with the single-agent results for NSAIDs and diuretics. By contrast, sacubitril/valsartan was the most common RAS inhibitor when combined with diuretics, frequently utilized for heart failure management. In triple whammy prescriptions, NSAIDs and diuretics patterns mirrored those of single-agents. The annual number of triple whammy prescriptions showed a statistically significant downward trend over the study period by the Mann–Kendall trend test (p = 0.048). Notably, sacubitril/valsartan was the leading RAS inhibitor (46/199 patients, 23%), showing a higher proportion than its single-agent use (7.4%). Heart failure patients prescribed these two causative drugs are highly vulnerable to “triple whammy” prescriptions. Awareness of inadvertent NSAID additions is warranted to mitigate potential AKI risks.

Background/Objectives: Malnutrition and undernutrition are critical health concerns associated with increased mortality and costs. Although these are distinct clinical concepts, they are often used interchangeably in clinical practice and are inconsistent with the diagnostic frameworks. This diagnostic ambiguity may obscure true patient profiles. This study aimed to clarify the real-world diagnostic patterns of malnutrition and undernutrition and identify associated drug prescription trends using a patient estimation database in Japan. Methods: We analyzed the AHI partners database of 2024. Patients were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, code E46. Sex differences were analyzed and stratified according to age group: older adults (≥65 years) and younger adults (15–39 years). Odds ratios (ORs) were used to identify associated drugs. Results: Of 96,673,453 patients, 216,652 were diagnosed with malnutrition and 77,100 with undernutrition. In both categories, older adults accounted for more than half of the patients. Notably, distinct diagnostic labeling patterns were observed by sex. Malnutrition predominated in women (58.8%), whereas undernutrition was more prevalent in men (70.6%). This male predominance of undernutrition was reversed in younger adults, where women showed higher proportions in both categories. Prescription analysis identified 31 drugs frequently prescribed to the study population. Enteral elemental formulas had the highest OR (89.7). Some psychotropic drugs were frequently prescribed to women. Conclusions: Diagnostic patterns varied by sex and age, potentially reflecting distinct practices in diagnostic labeling. These findings highlight the need for standardized frameworks to ensure consistent assessments and effective nutritional interventions.

Objective: Pharmacotherapy is a potential risk factor for undernutrition; however, the association between individual drugs and nutrition-related adverse reactions remains unknown. We aimed to explore drugs affecting appetite and taste using the Japanese Adverse Drug Event Report (JADER) database. Methods: JADER reports (April 2004–January 2025) were analyzed for drug safety signals across seven Preferred Terms (PTs): “Appetite disorder,” “Decreased appetite,” “Abnormal loss of weight,” “Ageusia,” “Dysgeusia,” “Hypogeusia,” and “Taste disorder.” Signal detected drugs were classified by therapeutic category, and their package insert information was reviewed. Results: Among 20,638 nutrition-related adverse reaction reports, signals were detected for 54, 14, 24, and 13 drugs for “Decreased appetite,” “Ageusia,” “Dysgeusia,” and “Taste disorder”, respectively. No signals were detected for the other three PTs. Regarding therapeutic category, other hormone preparations were common for “Decreased appetite,” while anti-viral agents were common for “Dysgeusia” and “Taste disorder.” Of these, five and 15 drugs lacked descriptions in the package inserts regarding decreased appetite and taste-related adverse reactions, respectively. Conclusions: This study clarified drugs that may affect appetite and taste, providing a focused list for early detection. These findings may enhance pharmacovigilance practices and inform clinical approaches for managing drug-induced nutritional concerns.

Introduction Diuretics are widely used in Japan for the treatment of hypertension and heart failure. Electrolyte disturbance is a common adverse reaction to diuretics and may be life-threatening. Previous studies have shown that diuretic-induced electrolyte disturbance is more common in women. Electrolyte balance is regulated by the kidneys, and renal function tends to decline with advancing age. Objective The aim of this study was to identify patients at high risk of adverse reactions to diuretics, considering the effects of sex, renal function, and age on susceptibility to diuretic-induced electrolyte disturbance. Methods Claims data for 67,135 patients on diuretics in Japan were sourced from DeSC Healthcare, Inc. The data covered the period from April 2020 to March 2021. Results Analysis of patient numbers using the chi-squared test showed that hyperkalemia was more common in men than in women (326 vs. 271; p = 0.003) and that hypokalemia was more common in women than in men (413 vs. 285; p < 0.001). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for women considering age and renal function (estimated glomerular filtration rate [eGFR]). In elderly patients aged ≥ 75 years, the odds of developing hypokalemia in women compared to men were 1.47 (95% CI 1.13–1.91) for eGFR 60–30 mL/min/1.73 m² and 2.05 (95% CI 1.08–4.10) for eGFR < 30 mL/min/1.73 m². Conclusion Among women aged ≥ 75 years, those in lower eGFR groups (60–30 and < 30) had higher odds of hypokalemia compared to men. These data highlight the importance of monitoring for adverse reactions to diuretics, particularly hypokalemia, in elderly women with low eGFR.

The package inserts of prescription drugs provide essential information for the proper administration of pharmacotherapy. The incidence of adverse reactions for several drugs is known to be higher in women than in men. However, no studies have examined whether information on gender differences is included in Japanese package inserts. Therefore, this study investigated information on gender differences in the package inserts of Japanese prescription drugs, using the drug information database JAMES provided by the Medical Information System Development Center and the Japan Pharmaceutical Information Center. Non-proprietary names of prescription drugs were yielded 1,679 in Japan. Of the 1,679 ingredients in package inserts of prescription drugs, 76 (4.5%) included information on gender differences. The number of inserts that contained information on gender differences in the "DOSAGE AND ADMINISTRATION," "ADVERSE REACTIONS," and "PHARMACOKINETICS" sections was 3, 16, and 62, respectively. Furthermore, in the "ADVERSE REACTIONS" section, 15 of the 16 inserts mentioned a higher frequency of adverse reactions in women compared with men. Importantly, most of the inserts with information on gender differences in the "PHARMACOKINETICS" section mentioned a higher area under the curve for women than for men. Most of the package inserts of prescription drugs with information on gender differences provide useful information aimed at preventing risks in women. However, there is an extreme lack of information on gender differences in the package inserts of prescription drugs in Japan, and we consider enhancing information on gender difference as an urgent issue.