Published papers

Background and Objectives: Oropharyngeal dysphagia (OD), a dysfunction in swallowing food or drink, can result from various diseases and adverse drug reactions. OD is a risk factor for aspiration pneumonia (AP). However, the specific drugs causing OD and their incidence rates are not fully understood. This study aimed to identify drugs associated with OD, their incidence rates, and AP risk factors in patients taking these drugs on the basis of the information provided in package inserts. Methods: This study identified candidate dysphagia-inducing drugs (CDIDs) from Japanese package inserts that listed OD as an adverse reaction. The age, sex, medications, and comorbidities of patients taking CDIDs were analyzed using the JammNet insurance database, purchased from JammNet Co., Ltd. (Tokyo, Japan). Results: Overall, 54 ingredients were identified as CDIDs. Out of 24,276 patients taking CDIDs, 146 (0.6%) were diagnosed with OD and 76 (0.3%) with AP. Among those with AP, 23 patients (30%) also had OD. OD or AP occurred in patients taking 28 (52%) of the 54 target ingredients. In addition, 13 ingredients had an adverse reaction incidence of 1% or greater for either condition. The top five CDIDs with the highest incidence rates for each diagnosis were clobazam, baclofen, zonisamide, tiapride hydrochloride, and topiramate. Incidence rates of OD and AP were significantly higher with multiple CDIDs than with a single drug (p < 0.05). Logistic regression analysis showed that AP occurrence was significantly associated with males, late-stage elderly individuals, a diagnosis of OD, and constipation. Conclusions: The results of this study suggest that careful attention should be given to the risk of AP when prescribing CDIDs, particularly for elderly male patients.

Several patients with advanced heart failure are prescribed a combination of diuretics and renin-angiotensin system (RAS) inhibitors. When dental clinics prescribe non-steroidal anti-inflammatory drugs (NSAIDs) to patients in this situation, it might result in a “Triple Whammy,” increasing the risk of acute kidney injury. This case report describes the first example of a novel dental-pharmacy cooperation model in Japan, designed to prevent the “Triple Whammy,” enabling both sides to claim medical service fees. We hereby report the case of a 80-year-old male patient with a history of heart failure, maintained on a diuretic and a RAS inhibitor. He was prescribed loxoprofen by a dentist at another pharmacy, resulting in the “Triple Whammy.” As a part of this cooperation model, the pharmacist utilized a new medication information inquiry form and shared details about the patient’s medications and clinical course with the dentist. The pharmacist proceeded to recommend acetaminophen as an alternative to NSAIDs, because it has minimal cyclooxygenase-2 (COX-2) inhibitory effects. It was later confirmed that the prescription had been changed. Dental–pharmacy cooperation should be strengthened for heart failure patients who receive both a diuretic and a RAS inhibitor, using this new tracing report option to prevent the “Triple Whammy” caused by NSAIDs prescribed at dental clinics.

Xerostomia is a condition characterized by the primary complaint of dry mouth, which can lead not only to oral issues but also to systemic diseases and a decline in quality of life (QOL). While drug adverse reactions are among its causes, the underlying mechanisms and risks associated with each medication remain unclear. Therefore, this study aimed to clarify aspects of drug-induced xerostomia using the Japanese Adverse Drug Event Report Database. Five Preferred Terms defined by the Japanese version of the Medical Dictionary for Regulatory Activities, including Thirst, Dry mouth, Dry throat, Lip dry, and Salivary hyposecretion, were classified as representing adverse reactions related to xerostomia and were extracted. An analysis of approximately 20 years of data revealed 781 cases were reported as xerostomia. Signals were detected for 27 drugs, classified into 10 categories according to the Anatomical Therapeutic Chemical classification. Of these, 20 drugs had xerostomia descriptions in their package inserts, and 12 drugs were assigned scores on the Anticholinergic Risk Scale. Signals were also detected for drugs not widely known to be associated with xerostomia, such as ANTINEOPLASTIC AGENTS and VACCINES, suggesting the influence of patients’ underlying diseases and concomitant medications. Both the newly identified seven drugs and those that do not exhibit anticholinergic effects should be evaluated in conjunction with further clinical data. Future investigations considering patients’ underlying conditions and concomitant medications are important. Furthermore, since xerostomia may impact QOL and systemic health, pharmacists are expected to play an active role in its prevention and early detection.

The importance of oral health has gained increasing recognition in the recent years owing to its association with numerous systemic diseases such as diabetes and cardiovascular disease. Dental checkups are crucial for maintaining and promoting oral health; however, in Japan, a relatively low uptake of dental checkups remains a challenge. Community pharmacists are expected to play a vital role in supporting the health and well-being of local residents; however, they have been observed to be reluctant to provide support in the oral health domain. This study aimed to develop and evaluate a blended learning training program on oral health support aimed at educating pharmacists working in health support pharmacies. The training, which involved online learning and on-site training, covered topics such as the importance of oral health, methods of oral health assessment, and the mechanisms of eating and swallowing. The participants, including a total of 39 pharmacists from across the country, completed surveys before and after the training, as well as at 9 months and 15 months posttraining. The results demonstrated a significant improvement in the pharmacists' knowledge, explanatory abilities, and confidence in providing oral health support, and these effects were observed to persist for up to 15 months after the training had ended. In addition, the variety of oral health-related products in pharmacies increased. This blended learning program demonstrates the potential to redefine the role of pharmacists in promoting oral health and contribute to the improvement of oral health among local residents.

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.

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.

This study aimed to assess the availability of renal function laboratory values in Japanese community pharmacies and examine their association with the prescription of drugs requiring dosage adjustment. In this cross-sectional observational study, data were obtained from the electronic medical records of a community pharmacy in Japan. A total of 389 eligible patients (aged ≥ 18 years) who visited the pharmacy in April 2024 were included. The primary outcome measures were the proportion of participants with available renal function laboratory values and those prescribed medications requiring dosage adjustment. A total of 128 patients (32.9%) were prescribed at least one medication requiring dosage adjustment, most commonly vitamin A and D preparations (32 cases) and antidiabetic agents (31 cases). Renal function laboratory values were available for 40 patients (10.3%). Compared to those not prescribed such drugs, patients receiving medications requiring renal-based dosage adjustments included a significantly higher proportion of older adults (70/128, 54.7% vs 98/261, 37.5%, p = 0.001) and patients with available laboratory values (20/128, 15.6% vs 20/261, 7.7%, p = 0.015). No patients were identified with the "Triple Whammy," which is known to significantly increase the risk of renal function deterioration. Community pharmacists endeavor to obtain renal function laboratory values for older adults, who are more likely to be prescribed medications requiring dosage adjustment. However, the proportion of cases with obtained laboratory values remains low. Pharmacists are expected to actively recommend renal function testing to physicians. Furthermore, they should contribute to safe pharmacotherapy by utilizing comprehensive patient information.

Purpose: The prevalence of migraine headache is higher in women. Low barometric pressure is a factor in headache triggering, but sex-related differences have not been identified. The purpose of this study was to examine sex-related differences in headache triggered by low barometric pressure. Methods: Study subjects aged 20–49 years were randomly selected from a research company’s (Macromill, Inc.) web panel. Those with chronic migraine or tension-type headache invited to complete a web-based self-administered questionnaire. Logistic regression analysis was performed with the objective variable as the Headache Impact Test-6 (HIT-6) high scores (56 or more) or headache triggered by low barometric pressure. Results: Participants were 332 women and 337 men in the headache population. HIT-6 high scores were associated with age at headache occurrence 20 years or younger (OR: odds ratio 1.85, 95% CI: confidence interval 1.15–2.99, p = 0.012) and headache triggered by low barometric pressure (OR 2.11, 95%CI 1.51–2.94, p < 0.001). Headache triggered by low barometric pressure was significantly associated with women (OR 2.92, 95%CI 2.12–4.02, p < 0.001). Conclusions: Headache triggered by low barometric pressure were related to sex-related differences. It was suggested that a sex-specific treatment approach for headache triggering is needed.

Expectations for pharmacists' contribution and involvement in pressure ulcer pharmacotherapy are growing. This study aimed to not only clarify the effects of incorporating practical training on the use of topical medications into clinical preparatory education but also examine the relationship between students' aspiration—or lack thereof—to pursue a career as a pharmacist. The percentage of positive responses to the questionnaire survey on knowledge, skills, and attitudes toward pressure ulcer treatment was significantly higher after the lecture than before and highest after the practical training. In addition, students who aspired to become pharmacists tended to provide a higher percentage of positive responses after the lecture. However, the gap between aspiring and non-aspiring pharmacists tended to narrow after practical training. These results suggest that incorporating practical training on pressure ulcer treatment into lectures improves students' knowledge, skills, and attitudes toward its treatment. Including practical training in pressure ulcer education may compensate for the difference in the educational effect of lectures between students who aspire to become pharmacists and those who do not, thereby improving the educational effect for the latter.

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.

Purpose: Loneliness is related to menstrual disorders and medication use. Loneliness and pain are related and may be associated with analgesic use. The aim of this study was to investigate the prevalence of concomitant analgesic use and overuse, and to clarify factors associated with loneliness and analgesic overuse among women who are low-dose estrogen-progestin (LEP) users. Methods: Women in their 20s and 30s were randomly selected from a research company’s web panel (Macromill, Inc.) and LEP users were screened. The survey included analgesic concomitant use days per month and the Three-Item Loneliness Scale (TIL). Logistic regression analysis was performed with high TIL score (≥ 6) and analgesic use ≥ 10 days per month as the objective variables. Results: A total of 516 valid responses from LEP users were analyzed. Among them, 64.1% reported concomitant analgesic use on ≥ 1 day per month, 11.2% on ≥ 10 days per month, and 45.7% had high TIL score. High TIL score was significantly associated with concomitant analgesic use on ≥ 1 day per month (odds ratio [OR] 1.76, 95% confidence interval [95%CI] 1.18–2.63, p = 0.006). Concomitant analgesic use on ≥ 10 days per month was significantly associated with endometriosis (OR 5.25, 95%CI 2.15–12.81, p < 0.001) and concomitant analgesic use for low back pain (OR 4.67, 95%CI 1.65–13.18, p = 0.04). Conclusions: To our knowledge, this is the first detailed study to investigate concomitant analgesic use and overuse among LEP users. Loneliness was found to be prevalent in this population and was associated with concomitant analgesic use, potentially reflecting underlying patterns of frequent or habitual analgesic intake. Furthermore, concomitant analgesic overuse was linked to conditions such as endometriosis and low back pain, underscoring the importance of medication monitoring that takes into account both loneliness and the self-recording of menstrual symptoms. Greater attention by healthcare professionals to the psychosocial context of concomitant analgesic overuse and loneliness may facilitate more meaningful patient dialogue and contribute to improved quality of life.

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.

Pharmacy practice experiences (PPEs) based on a revised model core curriculum for pharmaceutical education that incorporates outcome-based education have been implemented in Japan. PPEs is a 22-week period in both a community pharmacy and hospital and is characterized by “participatory and experiential learning,” “performance evaluation,” and “continuous involvement in eight representative diseases.” This mini-review describes the evaluation from preintroduction to implementation of PPEs. During the performance evaluation, using a rubric—consisting of a four-point score—for assessing pharmaceutical students’ performance instead of a rating scale of specific behavioral objectives was feasible. Pharmacist mentors and pharmaceutical students could measure the latter’s performance level and growth in PPEs at a community pharmacy or hospital using a rubric assessment. During the continuous involvement of eight representative diseases, sharing information tools between community pharmacies and hospitals substantially increased the implementation rate related to these eight diseases. Furthermore, experiences of eight representative diseases were considerably associated with the growth of pharmaceutical students’ performance. Results indicate that PPEs with which pharmaceutical students experience a wide range of involvement with eight representative diseases may effectively enhance their competencies.

Obtaining laboratory data on renal function in community pharmacies is challenging, as pharmacists rarely perform pharmaceutical interventions based on the patient’s renal function during over-the-counter (OTC) medication sales. This study aimed to identify OTC medications requiring caution in patients with impaired renal function using the Pharmaceuticals and Medical Devices Agency (PMDA) database. Moreover, we compared renal function-related cautionary notes in the package inserts of prescription drugs having the same composition. The analysis focused on the package inserts of OTC medications sold exclusively by pharmacists. Among these, 64% (9/14 cases) of pharmaceuticals requiring guidance (yo-shidou medication) and 80% (107/134 cases) of Category 1 OTC medications had renal function-related warnings in the “precautions for use (what you should not do/who should seek consultation)” section. For OTC medications containing famotidine and nizatidine, the dosage and administration were set lower than those for prescription drugs. Although these drugs can be used for patients with impaired renal function on prescription, their use is restricted as OTC medications. We believe that enabling self-checks of renal function at community pharmacies could expand the range of indications for OTC medications and promote notified self-medication.

Undernutrition is a common risk after surgery or during periods when oral dietary intake is challenging. Enteral nutrients, frequently utilized in nutritional management, are drugs associated with multiple contraindications involving pathology and allergy, and they require careful attention in dispensing. However, the occurrence of nutrition-related incidents in community pharmacies remains unknown. This study aimed to identify issues regarding the safety of pharmacotherapy in patients requiring enteral nutrition using the database of Project to Collect and Analyze Pharmaceutical Near-Miss Event Information. We highlighted the critical information that pharmacists should focus on to prevent accidents and elucidated the details and prescription drugs of cases that matched the search for “Nutrition (all included)” in Japanese. There were 475 cases reported between January 2009 and September 2023. Of these, 347 cases (73%) were classified as “inquiry about prescription and provision of information to prescribing physician” (Category II) and 115 cases (24%) were classified as “drug dispensing” (Category I). In both cases, the top five drugs were enteral nutrients. Among the life-threatening Category II cases, 9 cases were for pathological contraindications including severe liver or renal dysfunction, 6 cases were for adverse reactions including diarrhea, and 5 cases were for allergies or patient constitutions. Notably, the incidence of adverse reactions was higher than in data for the latest annual reports. Therefore, pharmacists should be mindful while dealing with prescriptions involving possible contraindications in patients requiring enteral nutrition. Pharmacists should contribute to the provision of safe pharmacotherapy by remaining vigilant against dispensing errors.

Xerostomia is a syndrome characterized by subjective or objective findings of oral dryness. One quarter of the elderly population suffers from xerostomia owing to a decline in salivary secretion function with age and problems with oral closure. Additionally, many ethical drugs have xerostomia listed as an adverse drug reaction. Xerostomia reduces the self-cleansing action of the mouth and can cause problems in maintaining oral health. In this study, we created a list of drugs associated with xerostomia from these package inserts. Then, electronic medical record data from Keio University Hospital were analyzed to investigate prescribing trends among elderly patients and to identify patient characteristics associated with these drugs. Patients who received continuous prescriptions from April 2019 to March 2020 were included in this study based on age, prescribed drugs, and associated diseases. Among the 575 patients analyzed, 464 (80.7％) were prescribed at least one xerostomia-inducing medication. Compared with the early-stage elderly, a significantly higher proportion of late-stage elderly patients received these medications (P < 0.001) and had multiple prescriptions (P < 0.001). Logistic regression analysis examined the presence and multiple prescriptions of xerostomia-inducing drugs, showing significant associations with late-stage elderly patients and polypharmacy. The most common conditions among patients prescribed xerostomia-inducing drugs were endocrine, nutritional, metabolic, cardiovascular, and gastrointestinal diseases. Accordingly, vasodilators, peptic ulcer drugs, and hyperlipidemic drugs were frequently prescribed to these patients. The results suggest that the risk of xerostomia should be a point of consideration when prescribing multiple medicines to elderly patients.

Background: Previously, we have demonstrated that human ABCB5 is a full-sized ATP-binding cassette transporter that shares strong homology with ABCB1/P-glycoprotein. ABCB5-transfected cells showed resistance to taxanes and anthracyclines. Herein, we further screened ABCB5 substrates, and explored the mechanism of resistance. Methods: Sensitivity of the cells to test compounds was evaluated using cell growth inhibition assay. Cellular levels of buthionine sulfoximine (BSO), glutathione and amino acids were measured using HPLC and an enzyme-based assay. Cellular and vesicular transport of glutathione was evaluated by a radiolabeled substrate. Expression levels of glutathione-metabolizing enzymes were assessed by RT-PCR. Results: Human ABCB5-transfected 293/B5-11 cells and murine Abcb5-transfected 293/mb5-8 cells showed 6.5- and 14-fold higher resistance to BSO than the mock-transfected 293/mock cells, respectively. BSO is an inhibitor of gamma-glutamylcysteine ligase (GCL), which is a key enzyme of glutathione synthesis. 293/B5-11 and 293/mb5-8 cells also showed resistance to methionine sulfoximine, another GCL inhibitor. A cellular uptake experiment revealed that BSO accumulation in 293/B5-11 and 293/mb5-8 cells was similar to that in 293/mock cells, suggesting that BSO is not an ABCB5 substrate. The cellular glutathione content in 293/B5-11 and 293/mb5-8 cells was significantly higher than that in 293/mock cells. Evaluation of the BSO effect on the cellular glutathione content showed that compared with 293/mock cells the BSO concentration required for a 50 % reduction in glutathione content in 293/B5-11 and 293/mb5-8 cells was approximately 2- to 3-fold higher. This result suggests that the BSO resistance of the ABCB5- and Abcb5-transfected cells can be attributed to the reduced effect of BSO on the transfectants. Cellular and vesicular transport assays showed that the transport of radiolabeled glutathione in 293/B5-11 cells was similar to that in 293/mock cells. The mRNA expression of genes encoding glutathione-metabolizing enzymes in 293/B5-11 cells was similar to that in 293/mock cells. The cellular content of Glu, a precursor of glutathione, in 293/B5-11 and 293/mb5-8 cells was higher than that in 293/mock cells. Conclusions: ABCB5/Abcb5-transfected cells showed resistance to BSO, which is not a substrate of ABCB5. Our results suggest that ABCB5/Abcb5 upregulates cellular glutathione levels to protect cells from various poisons.