Patients with reduced swallowing function have difficulty taking tablets in their original form. In such cases, tablets are crushed (crushing method) and administered through feeding tubes, but this practice may affect efficacy. A simple suspension method (SSM) has been widely used to address issues of administering crushed tablets through feeding tubes. Most of all angiotensin-converting enzyme (ACE) inhibitors are ester prodrugs. When they are suspended with magnesium oxide, ester prodrugs are hydrolyzed, and the active metabolite increases before absorption. In this study, we investigated the effects of SSM and crushing methods on the pharmacokinetics of the ACE inhibitor using temocapril and magnesium oxide. A human clinical trial was conducted to compare the pharmacokinetics of temocapril and magnesium oxide in three groups in six healthy adult men (period 1, tablet group; period 2, SSM group; and period 3, crushing-and-mixed group). The pharmacokinetics of temocaprilat, which is the active metabolite, were examined. The AUC_0-24 and C_max of the SSM group were 89.3％ and 86.1％ compared with those of the tablet group, whereas those of the crushing-and-mixed group decreased to 73.0％ and 78.9％, respectively. In the crushing-and-mixed group, the concentration of temocapril decreased during crushing and long-term storage. Findings in the present study suggest that the crushing method may decrease in AUC_0-24 and C_max and that the expected drug effect may not be achieved. For ester prodrugs, the use of SSM might be considered rather than the crushing method.

Studies have indicated that the rise in clarithromycin (CAM) resistance in Helicobacter pylori is a reason for the decline in H. pylori eradication success. We instituted a pharmacist-led antimicrobial stewardship (AS) program to reduce treatment failure due to CAM-resistant H. pylori. In this retrospective single-center study, we evaluated the efficacy of this program by comparing initial eradication rates (primary outcome) for CAM-resistant H. pylori infections between two groups, namely, the non-AS group (from May 1, 2015, to December 31, 2018) and the AS group (from January 1, 2019, to December 31, 2020). The results showed that compared with the non-AS group, the AS group had a significantly higher initial eradication rate (80.0％ (116/145 cases) vs. 94.9％ (37/39 cases), respectively, P = 0.028); a significantly lower total drug cost (6,624.7 yen(6,392.3 - 6,624.7) vs. 6,392.3 yen (6,392.3 - 6,392.3), respectively, P < 0.001). These findings suggest that pharmacist-led AS programs for the treatment of CAM-resistant H. pylori infections can improve the initial eradication success rate and have a positive pharmacoeconomic impact.

Depakene^® fine granules (Depakene) that contain 40％ sodium valproate have a high sedimentation rate and poor suspension dispersibility. Administration of Depakene suspension via a commonly used nasal 8-Fr outer diameter feeding tube results in tube blockage. The study aimed to determine if the addition of thickened food to Depakene would prevent tube blockage observed with Depakene suspension alone. We tested a 1 g / 20 mL Depakene suspension with the addition of various concentrations of thickened food and measured the dissolution profile and tube passage amounts of sodium valproate. When the concentrations of thickened food were ≤ 2％, the dissolution profile and tube passage amount of sodium valproate were not affected. In a questionnaire survey on the sensation of injecting the Depakene suspension into a tube, most respondents said that a 0.38％ thickened food concentration was the “easiest to inject,” with infrequent tube blockages. Since the plunger pressing force for the 0.38％ thickened food concentration was about 12 N, it was regarded as the load that an adult woman could easily inject into the tube. To summarize, we found that a thickened food concentration of 0.38％ effectively prevented tube blockage of a 1 g / 20 mL suspension of Depakene.

In recent years, many drugs with characteristic side effects, such as molecular target drugs, are used in cancer chemotherapy. Continuous side effect monitoring and management are required not only during hospitalization, but also in outpatient treatments. Therefore, pharmacists at our hospital conduct interviews with hepatocellular carcinoma patients receiving lenvatinib (LEN) before they are examined by a doctor. In the present study, to evaluate the effectiveness of outpatient pharmacist interventions, the treatment continuation rate within 6 months of the initiation of LEN administration was compared between an intervention group (n = 45) and non-intervention group (n = 47). The treatment continuation rate (event: adverse events or progressive disease (PD)) was higher in the intervention group (P < 0.05). No significant differences were observed in the discontinuation rate due to PD, whereas that due to adverse events was lower in the intervention group. Within 2 months of treatment initiation, the discontinuation rate due to adverse events was 21.4％ in the non-intervention group, but 0％ in the intervention group. No significant differences were noted in the incidence of adverse events during the observation period, the initial dose of LEN, relative dose intensity, or hepatic reserve. Furthermore, the acceptance rate of proposals by pharmacists to doctors was 87.5％, with the highest rate for supportive care proposals. These results suggest that interventions by pharmacists contributed to an increase in the treatment continuation rate. Moreover, interventions were considered to be useful for preventing early discontinuation due to adverse events.

Obinutuzumab, a novel glyco-engineered anti-CD20 monoclonal antibody, has been developed to have superior efficacy to rituximab. Although obinutuzumab frequently causes infusion reactions (IR) during initial administration, there have been few reports about the frequency and risk factors for IR. In this study, we investigated the frequency of clinically relevant IR during obinutuzumab administration and explored the risk factors associated with obinutuzumab-induced IR. We included patients who were administered obinutuzumab for CD20⁺ B-cell non-Hodgkin lymphoma treatment at the Department of Hematology in Tenri Hospital from September 2018 to September 2020. Twenty-five patients were included (13 men and 12 women) and their median age was 68 (49 - 81 years). Nine (36％) of these patients developed IR (grade ≧ 2). Comparison of patient characteristics between IR and non-IR groups showed that the incidence of IR during obinutuzumab administration was related to soluble interleukin-2 receptor (sIL-2R) and lactate dehydrogenase (LDH) levels. The results of ROC curve analysis revealed the cut-off values of sIL-2R and LDH were 3,201 U/mL and 260 U/L, respectively, and AUC of ROC curve for sIL-2R and LDH were estimated at 0.75 and 0.72, respectively. The higher IR incidence was detected when sIL-2R levels exceeded 3,201 U/mL. In addition, the number of patients who developed IR at sIL-2R ≧ 3,201 U/mL and/or LDH ≧ 260 U/L was larger than that at sIL-2R ≧ 3,201 U/mL. The combined biomarker, sIL-2R and LDH may be useful for prediction of the occurrence of IR after the initial administration of obinutuzumab.

The “Japanese Clinical Practice Guidelines for antimicrobial prophylaxis in surgery” were issued in June 2016. The pharmacist (essential in the antimicrobial stewardship team at Ogaki Municipal Hospital), in collaboration with the clinical department, prepared the antimicrobial prophylaxis in surgery based on the guidelines and provided daily monitoring and feedback-based interventions to patients prescribed with antimicrobial prophylaxis. In this trial, we compared the outcomes before and after the modification of antimicrobial prophylaxis in transurethral endoscopic surgery. The number of patients undergoing surgery before and after modification were 365 and 495, respectively. The number of preoperative urine cultures performed significantly increased from 10.1％ to 21.2％. Of the urine cultures performed after the modification, 8.6％ were resistant to cefazolin; however, all these cases had their antimicrobials modified based on the antibiotic susceptibility test results. Before and after modification, the compliance rates were 88.5％ and 89.7％, respectively; and the incidence of postoperative urinary tract infections (UTI) was 3.0％ and 3.2％, respectively. There was no significant difference in the foregoing factors. The cost of antimicrobial agents per operation was ￥1,187, which was reduced to ￥337 after the modification. We propose that pharmacists change the clinical pathway of antimicrobial prophylaxis in cooperation with clinical departments to improve compliance rates. Furthermore, implementation of antimicrobial based daily monitoring and feedback-based interventions is important as it encourages performance of preoperative urine cultures and enables proper administration of appropriate antimicrobials based on the results. Consequently, control of postoperative UTI and the reduction of antimicrobial usage costs will ensue.