The interactions between 4 compounds used as influenza neuraminidase inhibitors—oseltamivir, zanamivir, laninamivir, and peramivir— and influenza virus neuraminidase were analyzed using pair interaction energy decomposition analysis based on fragment molecular orbital (FMO) method, quantitatively elucidating binding characteristics of each inhibitor. Our calculations revealed that structures with common functional groups showed similar binding characteristics, whereas structures with functional groups differing in hydrophilicity/hydrophobicity showed different types of intermolecular interactions for the same amino acid residues. Such analysis is expected to be effective for precise molecular design in structure-based drug design.

Amiodarone (AMD) is characterized by complex pharmacokinetics involving high lipophilicity and extensive protein binding. Serum AMD concentrations are influenced by triglyceride (TG) levels. Although the impact of TG on AMD concentrations at steady state has been previously investigated, data regarding the initial treatment period are limited. Given the prolonged half-life of AMD and the need for dose adjustments prior to reaching steady state, elucidating the effect of TG during this early phase is important. This retrospective study analyzed 64 patients who received AMD therapy at Sapporo City General Hospital between January 2016 and December 2024. Serum levels of AMD, its active metabolite desethylamiodarone (DEA), TG, and albumin were measured during the initial period (4–6 months) and steady-state period (7–12 months). Concentration-to-dose (C/D) ratios were calculated to assess pharmacokinetic variability during each period. Significant positive correlations were observed between serum TG levels and C/D_AMD during the initial (r=0.424, p<0.05) and steady-state (r=0.492, p<0.01) periods. A modest but significant correlation was observed between TG and C/D_DEA during the steady-state period (r=0.304, p<0.05). No significant correlations were found between albumin and C/D_AMD or C/D_DEA at any period. Serum TG levels affected AMD concentrations from the initial treatment period; however, the pharmacologically active unbound fraction remained stable. Consequently, dose adjustments based solely on fluctuations in TG levels are not required during the initial period. These findings contribute to the development of more precise AMD dosing strategies to maintain antiarrhythmic efficacy from treatment initiation.

It is no exaggeration to say that most biological processes are carried out by proteins. However, proteins in the cells of many animals, including humans, will be damaged by various non-physiological modifications with age. The accumulation of such damaged/abnormal proteins is thought to cause a decline in the physiological function of various tissues in aging individuals. To maintain normal physiological function, abnormal proteins must be restored to normal by repair enzymes or removed by protein degradation enzymes, and new molecules must be synthesized and replaced. However, the transcription factors responsible for inducing heat shock proteins involved in the repair of conformationally altered proteins and molecules in the proteasome involved in the degradation of damaged proteins, are altered with age as well. In other words, those proteins involved in maintaining the homeostasis of proteins are also altered themselves with age. This review summarizes the author’s 44 years of research on “aging and proteostasis.”

Oral lichen planus (OLP) causes chronic pain and functional limitations. In a randomized, placebo-controlled crossover trial of ibuprofen gargle, short-term analgesia on the visual analog scale (VAS) was not statistically significant, although patient-perceived functional gains were suggested. This study aimed to characterize the long-term patient-centered response patterns to ibuprofen gargling using predefined responder definitions. We performed a secondary exploratory analysis of a single-center trial and its long-term extensions (jRCTs051220009 and jRCTs051220010). Twenty-four participants were followed up on day 176. Endpoints combined within-day analgesia on VAS at 0, 5, and 15 min (VAS₀, VAS₅, VAS₁₅) with multidimensional symptoms from the 10-item Patient-Reported Oral Mucositis Symptom (PROMS) scale. Time-to-first achievement (TFA) was summarized, and responses were evaluated descriptively and visually. Overall PROMS response (Definition C) occurred in 21/24 participants (median TFA, 5 d). Domain-level responders were frequent (e.g., pain domain D 20/24, eating domain F 18/24; both median 5 d). In contrast, fewer participants met VAS-based endpoints: A 16/24 (between-day VAS) and B 17/24 (within-day VAS) over the observation period. Visual summaries suggested that improvements tended to emerge early and were sustained or recurrent across subsequent weeks in some participants. Although immediate analgesia was modest, this exploratory analysis indicated that regular use of ibuprofen gargling may be associated with early and durable improvements in patient-reported symptoms and function in OLP. These exploratory findings suggest that patient-centered endpoints may be useful for evaluating topical NSAIDs, and should be examined in future studies with larger sample sizes.

In Japan, amrubicin hydrochloride (AMR) is occasionally administered to patients with recurrent small cell lung cancer (SCLC). AMR therapy can induce febrile neutropenia (FN), a complication that may be fatal or compromise therapeutic efficacy due to treatment interruption or dose reduction. Identifying risk factors for FN is therefore critical to ensuring safe and effective AMR administration. Current evidence on this issue remains limited to small case series, underscoring the need for more robust studies. We conducted a multicenter retrospective analysis to examine predictors of FN during AMR treatment for recurrent SCLC. Patients who received AMR between April 1, 2013, and March 31, 2023, were included. The cohort comprised 256 patients, divided into 192 without FN and 64 with FN. Multivariate analysis demonstrated that performance status (PS) >2 (odds ratio: 5.8, 95% confidence interval: 1.70–19.80, p=0.005) and hematocrit (HCT) (odds ratio: 0.93, 95% confidence interval: 0.877–0.994, p=0.033) were significantly associated with FN development. These findings suggest that PS and HCT may serve as key indicators for predicting FN during AMR therapy in patients with recurrent SCLC.

In response to the rapid advancement of digital transformation (DX) in healthcare, pharmacists are increasingly expected to interpret and apply electronic health record (EHR) information to support clinical decision-making and patient care. Despite this shift, the integration of educational EHRs into pharmacy curricula remains limited, and their educational effectiveness is underexplored in Japan. This study implemented a structured EHR-based educational program for fourth-year pharmacy students and evaluated its impact on their clinical reasoning, interprofessional perception, and information and communications technology (ICT) literacy. Nineteen students participated in a 240-min program, featuring a pediatric Kawasaki disease case, and utilizing an educational EHR platform. The instructional design included case analysis, group discussion, role-play, and reflection. Educational outcomes were assessed using pre- and post-intervention tests; rubric-based performance evaluations; Attention, Relevance, Confidence, and Satisfaction model questionnaires; and qualitative analysis of open-ended feedback. Statistical analysis using the Wilcoxon signed-rank test revealed significant improvements in knowledge and performance metrics (p<0.05). Students reported high motivation and satisfaction, and qualitative findings highlighted the program’s effectiveness in fostering clinical thinking and team-based care perspectives. However, feedback also suggested the need for workload balance and instructional pacing refinement. These findings indicate that an EHR-based program can serve as a valuable model for developing essential competencies in pharmacy education aligned with evolving professional roles. Future iterations may benefit from incorporating flipped classroom elements, repeated exposures, and diversified assessment strategies to enhance long-term learning outcomes.

Piperacillin/tazobactam (PIPC/TAZ) and vancomycin (VCM) are frequently used in combination (PTV) to manage severe healthcare-associated infections, but are also associated with an increased risk of acute kidney injury (AKI). In 2019, Ogaki Municipal Hospital implemented pharmacist-led interventions aimed at reducing PTV use and mitigating AKI. This study evaluated the impact of these interventions on antibiotic safety and patient outcomes. This retrospective study included hospitalized patients treated with PTV between January 2010 and December 2023. Details of these pharmacist interventions were reviewed retrospectively. Patients were categorized into pre- and post-intervention periods. The primary outcomes reported were the duration of PTV therapy and the incidence of AKI. Multivariable regression analyses were performed to evaluate the association between the intervention, therapy duration, and AKI incidence. Mediation analysis was conducted to assess whether the reduction in PTV duration mediated the effect of the intervention on AKI incidence. As a result, AKI incidence decreased from 19.8% in the pre-intervention period to 7.7% in the post-intervention period (p=0.038). In the PTV cohort, multivariable models showed lower AKI risk in the post period [adjusted odds ratio (OR) 0.283; 95% confidence interval (CI) 0.086 to 0.803; p=0.024] and a shorter PTV duration (β=−2.011 d; 95% CI −3.459 to −0.563; p=0.007). In mediation analysis, the shortening of PTV duration partially mediated the AKI reduction (ACME p=0.016). In conclusion, pharmacist-led interventions effectively reduced PTV duration leading to a decrease in AKI incidence, highlighting the critical role of pharmacists in promoting antimicrobial stewardship and improving patient outcomes.

While drugs affecting stroke rehabilitation outcomes have been studied in the context of convalescent hospitals, data on acute stroke patients remain insufficient. This retrospective single-center study aimed to evaluate the impact of medications on functional outcomes during rehabilitation in acute stroke patients. The study included stroke patients who received rehabilitation between April 2017 and March 2018. A total of 144 patients (mean age: 70.6±12.3 years; male/female: 86/58) were analyzed, including 101 with cerebral infarction (mean age: 72.3±12.1 years; male/female: 65/36) and 43 with cerebral haemorrhage (mean age: 66.7±12.1 years; male/female: 21/22). Multiple regression analysis was used to identify associations between drug use and recovery of activities of daily living (ADL). Multiple regression analysis of the overall data identified the use of non-steroidal anti-inflammatory drugs (NSAIDs) as a promoting factor for ADL recovery [partial regression coefficient (PRC): 34.52, p<0.01] and the use of angiotensin-converting enzyme inhibitors (ACE-Is) as an inhibiting factor (PRC: −36.33, p<0.01). In the cerebral infarction group, only ACE-I use was identified as an inhibiting factor (PRC: −28.85, p<0.01). In the cerebral haemorrhage group, NSAID use was identified as a promoting factor (PRC: 51.27, p=0.01), while the use of diabetes drugs was identified as an inhibiting factor (PRC: −39.82, p=0.046). Our results suggest that certain drugs influence functional recovery after stroke. However, further research is needed to understand the underlying mechanisms.

Lansoprazole is a proton pump inhibitor (PPI), frequently used for the treatment of gastroesophageal reflux disease. It may also be used in pregnant women; however, the safety of lansoprazole exposure during pregnancy remains unclear. In this study, we assessed the risk of major malformation and the effects on other pregnancy and birth outcomes resulting from lansoprazole exposure during the first trimester based on data from two Japanese facilities that provided counseling on drug use during pregnancy between 1988 and 2017. The study included 106 cases of lansoprazole exposure and 1788 control individuals. The risk of major malformation following exposure to lansoprazole after the first trimester was compared with that of the control group administered non-teratogenic drugs during the first trimester. The incidence of major malformation in singleton liveborn infants was 1.0% (1/96) in the lansoprazole group and 1.9% (31/1670) in the control group. Adjusted multivariable logistic regression analysis revealed no significant difference in the incidence between the control and lansoprazole groups [adjusted OR: 0.51 (95% confidence interval: 0.07–3.79), p=0.507]. Furthermore, no differences were observed between the two groups in the incidence of stillbirth, miscarriage, and birth weight. The results indicate that lansoprazole exposure during the first trimester is not associated with an increased risk of major malformations. Overall, our findings provide valuable insight for selecting gastroesophageal reflux disease medications for use in pregnant women.

Direct involvement of community pharmacists in the sale of OTC medicines is expected to help prevent adverse drug reactions (ADRs) and enhance treatment efficacy. However, the extent of their actual involvement in OTC medicine sales remains insufficiently investigated. To address this, we retrospectively analyzed OTC medicine sales survey forms to assess the involvement of community pharmacists in OTC medicine sales, and identify drug-related problems (DRPs) requiring pharmaceutical decisions. All customers who visited the Yokohama Nishiguchi branch of WinPharma Co., Ltd. to purchase OTC medicines were included in the study. Community pharmacists were involved in all OTC medicine sales. Among the 821 customers who sought specific OTC medicines, product choice was changed based on pharmacist recommendation in 124 cases (15.1%), including cases recommended to visit a doctor. Frequency of product change was highest for second-class OTC medicine sales. In addition, contraindications (21.0%) were the most common DRPs, with second-class OTC medicines accounting for 80.8% of all these cases. Furthermore, when including the 666 cases in which community pharmacists were consulted directly about purchasing OTC medicines, 790 of the 1487 cases (53.1%) required pharmacist involvement. These findings highlight the crucial role of community pharmacists preventing ADRs and enhancing treatment efficacy based on OTC medicines characteristics and conditions and lifestyles of users regardless of the risk classification of OTC medicines. Proactive involvement by community pharmacists can improve self-medication safety and efficacy by ensuring the proper use of OTC medicines.

Since pharmacy is a discipline based on natural and life sciences, learning about pharmacy is considered useful for science students outside this field. In this survey, we investigated whether pharmacy lectures delivered to students majoring in life sciences were useful for their studies within their respective fields. A questionnaire was sent to the students enrolled in the course, asking them to evaluate, on a five-point scale, whether the lectures were helpful in deepening their learning in their field of study, both overall and for each lecture theme. Additionally, we conducted a Customer Satisfaction (CS) analysis, using the overall evaluation of the lectures as the objective variable and the evaluation of each lecture theme as the explanatory variable. The response rate was 75.0% (72/96). Overall, 98.6% of the respondents found the lectures helpful in deepening their learning in their field of study. The satisfaction rate for each lecture topic exceeded 80%. When the CS graph was created, the lecture themes categorized as “priority maintenance field” were “Pain, psychology, analgesics, psychotic drugs” and “Adverse event.” In contrast, the themes identified as “priority improvement field” were “Hypertension and the therapeutic agent” and “Drug interactions.” These findings suggest that pharmacy lectures might be useful for deepening the learning of students majoring in life sciences.

The primary aim of this study is to examine whether the appearance of pharmacists in Japan is an issue worthy of discussion. A web-based survey was conducted in June 2023 among 500 men and women aged 25–74 (male/female ratio=1 : 1, equally assigned to five age categories). The respondents were asked about their trust in eight pictures of male pharmacists with different appearance factors (trust scale: seven questions, 6-point response). The pictures were combined using an orthogonal table for five factors (hair color (black and brown), hair length (normal and long), accessories, white coat condition (clean and dirty), and clothing under white coat (Y shirt+tie, Y shirt+T-shirt)). The data were analyzed through conjoint analysis. The median age of the 500 respondents was 50.5 (38–62) years. The highest mean confidence score for each of the eight images was 28.8(SD6.4) and the lowest was 16.1 (SD7.1). Conjoint analysis indicated that the relative importance of clothing and hair to trustworthiness was 50.9% and 33.8%, respectively. The condition of the white coat was high at 29.1%. The level utilities scores were 0.341 for “Y-shirt” and −0.008 for “Y-shirt+tie” for clothing under the white coat. Notably, cleanliness of the white coat had a greater impact than hair color or length. The results indicate that the appearance of male pharmacists significantly affects initial trust. Thus, appearance standards for pharmacists, including females, should be actively discussed.

Community pharmacists play a vital role in delivering person-oriented services, such as addressing prescription inquiries, providing home care services, and conducting medication follow-ups. Despite their significance, no nationwide surveys have assessed the efficacy of these pharmaceutical activities. Therefore, this study aimed to collect information on these three pharmacist tasks and investigate their effectiveness in preventing serious adverse drug reactions and reducing medical costs. Ten percent of insurance pharmacies in each prefecture were randomly selected to participate in the survey. Data were collected on basic pharmacy information, prescription inquiries, home care services, and medication follow-up, which spanned from 12 June to 18 June 2023. Of the 561 pharmacies pre-registered for the study, valid responses were obtained from 433 pharmacies (77.2%). The reported cases included 3064 prescription inquiries, 765 home care services, and 326 medication follow-ups. Prescription inquiries prevented serious adverse drug reactions in 122 cases, home care services in 209 cases, and medication follow-ups in 13 cases. The cost reductions associated with these activities were ¥28291790, ¥58285600, and ¥2544950, respectively, resulting in a total cost reduction of ¥89122340. The annual cost reduction was ¥33229078321.7, assuming a severity rate of 6.7%. The estimated annual reduction in medical costs specifically attributed to prescription inquiries was ¥8732177830. This study indicates that pharmacists prevent adverse drug reactions and contribute to the safety of drug treatment through prescription inquiries, home care services, and medication follow-up. These tasks reduced annual medical costs by approximately ¥42 billion, highlighting the economic and healthcare benefits of community pharmacy services.

Lemborexant, an orexin receptor antagonist (ORA), was introduced as a safer sleep medication at our hospital, but its prescription rate remained low. To address this issue, promotion of ORAs began in August 2022. This study aimed to evaluate the impact of these activities on the number of patients prescribed lemborexant. And it aimed to evaluate prescription conditions non-benzodiazepine drugs (NBDs) and delirium treatment antipsychotics (DTAs). The study spanned from August 2021 to March 2024, with August 2022 serving as the intervention point. The drugs analyzed included lemborexant, zolpidem and eszopiclone (NBDs), and risperidone and quetiapine (DTAs). Analyzed using interrupted time-series analysis, and assess changes in the number of patients prescribed these medications and the number of patients with abnormal indications. The promotion of ORAs significantly increased lemborexant prescriptions [level change 18 (95% confidence interval 0.07 to 35: p=0.049), slope change 2.7 (0.57 to 4.9: p=0.015)]. Concurrently, prescriptions for NBDs decreased [level change −56 (−86 to −25: p<0.001), slope change −30 (−54 to −5.7: p=0.017)], and the slope change for DTAs with abnormal instructions also decreased [−1.2 (−2.3 to −0.11: p=0.032)]. No significant differences were found for the other items. Promoting ORAs increased its use, and led to a reduction in the prescriptions of NBDs and DTAs with abnormal indications. Although there was no change in patient conditions, given the adverse effects associated with NBDs and DTAs these changes suggest a shift toward safer drug treatment practices.

LM1010, a high-performance liquid chromatography system for therapeutic drug monitoring (TDM) of various agents in clinical practice, is currently approved in Japan. Unlike conventional systems, LM1010 can rapidly measure clinical samples, and data analysis is based on the absolute calibration curve method and fully automated. However, the analytical performance of the LM1010 for the measurement of serum concentrations of linezolid (LZD) has not yet been evaluated. In this study, we aimed to evaluate the analytical performance of LM1010 and confirm the long-term stability of LZD at −30°C. One hundred forty-eight serum samples were collected from 25 patients (17 men and 8 women) who received LZD. Serum concentrations of LZD were measured using LM1010 and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three LM1010 instruments were used to confirm the differences in the measured values. A Passing–Bablok regression analysis demonstrated a strong correlation between LM1010 and LC-MS/MS (r=0.991), and comparable results were observed among the three LM1010 instruments (r=0.982–0.998). Bland–Altman analyses revealed that the average difference between LM1010 and LC-MS/MS methods was 1.7%, and similar results were observed among the three LM1010 instruments. The long-term stability of serum LZD in samples stored at −30°C for 48 weeks was also confirmed. These results suggest that LM1010 can be used for TDM of LZD in clinical practice.

Durotep^®MT Patch (DMTP) (Janssen Pharmaceutical K.K., Tokyo) is a systemically acting narcotic patch containing fentanyl. It is applied transdermally and removed 72 h after applying. The range of effective serum fentanyl concentrations is very narrow (0.3–3 ng/mL). Therefore, analysis of the absorption kinetics (ABK) is especially important. We studied ABK for fentanyl from DMTP 16.8 mg. There are 5 analytical methods to obtain ABK: The estimated mean absorbed rate at steady state (EMARSS) obtained using the residual method (standard value), absolute bioavailability method, Wagner–Nelson method, 3-compartment model Loo–Riegelman method (3LR), and SPLINE–Deconvolution method (SDecon), yielding results of 0.104, 0.119, 0.114, 0.109, and 0.103 mg/h respectively. EMARSS for 3LR and SDecon were nearly equal to the standard value. The absorbed rate for fentanyl with elapsed time by SDecon indicated an amplitude of 3 times with about a 20 h period at 10.7–72 h and the increase in the absorption rate began before the increase in the serum concentration when DMTP was applied transdermally. This phenomenon indicates that the mean absorption rate was constant; thus, an absorption steady state was reached. The actual mean absorption rate during this period was 0.0924 mg/h (range: 0.0594–0.131). The cumulative absorption ratio increased gradually with only a small amplitude, and bioavailability was 44.2%. From our results, SPLINE–Deconvolution is the most suitable method to assess fentanyl absorption kinetics of DMTP.

Active vitamin D₃ (VDRAs) can cause drug-induced hypercalcemia and acute renal failure. Eldecalcitol (ELD), a VDRA, promotes bone formation more strongly than other VDRAs, such as alfacalcidol (ALF), but whether or not ELD affects serum calcium (Ca) levels and renal function more significantly than other VDRAs is unclear. In Japan, the supply of ALF was temporarily stopped in 2021, and patients at Fukuoka University Hospital who were taking ALF were either switched to ELD or discontinued ALF. We retrospectively investigated how these prescription changes affected serum Ca levels and renal function. Sixty-seven adult patients who were admitted to our hospital for at least 5 d between September 2021 and March 2022 and were taking ALF at the time of admission were divided into 3 groups: 36 patients who continued ALF (ALF-C), 12 who were switched to ELD (ELD-S), and 19 who discontinued VDRAs (DC). The changes in weekly serum Ca levels and renal function during hospitalization were compared between the groups. At the second week of observation, the change in the serum Ca level was 0.01 mg/dL in the ALF-C group, +0.45 mg/dL in the ELD-S group, and −0.37 mg/dL in the DC group, showing a significant difference among these groups. In addition, serum Ca levels were increased in all patients in the ELD-S group at Week 2. The estimated glomerular filtration rate didn’t change significantly in any group during hospitalization. These results suggest that serum Ca levels should be measured by Week 2 when ELD is newly started or changed.

In this study, we assessed the information sharing practices between pharmacists and multidisciplinary healthcare professionals such as doctors, care managers, and nurses, and others. We evaluated the effectiveness of “home medical care management guidance reports” and “home-visit drug management guidance reports” prepared by pharmacists. We also identified factors that could enhance collaborative practices. To improve the reports, we introduced a new report form with an overview column and a reply column. We used the SOAP format in the new reports. We found that the response rate for reports from X pharmacy was significantly higher than that of Y pharmacies. A survey revealed that X’s reports contained more categories (median of 3 versus 1 in Y’s reports). Pharmacy X’s reports had a smaller proportion of pharmacotherapy details, and a larger proportion of information regarding patients’ living and health conditions, as well as environmental factors. We also found that the character count in X’s assessment column was significantly greater (168.5 versus 60), and notably less in the overview sections (12 versus 22) when compared to Y’s reports. Suggestions and guidance constituted a significantly larger portion of X’s reports (29.8% compared to 10.8% in Y’s). Questionnaire feedback from other healthcare professionals to whom the subject pharmacies send reports highlighted the importance of pharmacist-provided information on health and living conditions, based on pharmacological knowledge. Based on these results, to enhance health information sharing, pharmacists should integrate assessments of pharmacotherapy with health and living conditions and effectively communicate this information to other professionals.

Introduction: This study examines current OTC pharmaceuticals in Japan categorized as potential substances for abuse and discusses future initiatives for drug abuse prevention. Methods: The Pharmaceuticals and Medical Devices Agency package inserts search function was used to identify OTC pharmaceuticals containing substances prone to abuse. Subsequently, the corresponding OTC pharmaceuticals containing the designated ingredients were investigated, analyzing their therapeutic and risk categories. Results: In total, 1427 (13.9%) OTC pharmaceuticals contained the designated ingredients, with those containing methylephedrine and dihydrocodeine accounting for the majority (1245/1427, 87.2%). Among the therapeutic categories, oral cold medicines were predominant at 564, followed by antitussives and expectorants at 213, and oral rhinitis medicines at 100. Regarding risk categories, designated schedule II pharmaceuticals predominated in 9 out of 11 therapeutic category classifications. Conclusion: Designated schedule II pharmaceuticals, such as oral cold medicines, antitussives and expectorants, and oral rhinitis medicines, pose a high risk of drug abuse. Addressing this challenge necessitates collaboration between pharmacists and registered sales clerks to implement preventive measures aligned with current trends in drug abuse.

Pemetrexed is a folate analog inhibitor for the treatment of non-small-cell lung cancer (NSCLC). Prophylactic supplementation with vitamin B₁₂ and folic acid reduces hematotoxicity associated with pemetrexed. Metformin, the antidiabetic agent, has been associated with the potential side effect of vitamin B₁₂ deficiency. This retrospective observational study aimed to evaluate the effect of concomitant metformin use on hematologic adverse events in patients with NSCLC undergoing pemetrexed-based chemotherapy using the Medical Data Vision Database. Patients with stage III or higher NSCLC who received pemetrexed from April 2008 to May 2021 were categorized into metformin-treated (MTF) and non-metformin-treated (non-MTF) groups. The primary outcome was the proportion of granulocyte colony-stimulating factor (G-CSF) administration during cycle (C) 1 to C2 or C2 to C3 of pemetrexed therapy. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. A total of 1174 patients met the inclusion criteria (54 in MTF and 1120 in non-MTF). After PSM, 52 patients were included in each group. The median metformin dosage in the MTF group was 500 mg/d before and 625 mg/d after PSM. There were no significant differences between the MTF and non-MTF groups in G-CSF administration (15.4 vs. 21.2%, p=0.446). Multivariate logistic regression analysis also showed that metformin use did not significantly affect hematologic toxicity (odds ratio: 1.208, 95% CI: 0.554–2.634). This suggests that the concomitant use of a relatively low dose of metformin is unlikely to significantly increase the risk of hematotoxicity in Japanese patients with NSCLC receiving pemetrexed-based chemotherapy.