Warfarin (WF) has interactions with various drugs that alter its anticoagulant effect and this also applies to anti-cancer agents. However, interactions between WF and paclitaxel-carboplatin combination therapy (TC therapy) have not been adequately studied up till now. In view of this, we investigated such drug interactions in patients on WF who were receiving TC therapy at Kobe University Hospital from 1 February 2005 to 31 January 2010. As subjects, 17 patients in whom WF dosing had been stabilized prior to initiation of TC therapy were selected. Changes in the anticoagulant effect of WF due to TC therapy were investigated retrospectively. The pro-thrombin time international normalized ratio (PT-INR) significantly increased (from 2.00 to 2.58 (p <0.05)) after the initiation of TC therapy. However, this increase seemed to be transient. The PT-INR level peaked a few days after TC therapy, and then returned to normal within a few days. Furthermore, in patients who received additional concomitant drugs with known WF interactions, there was a tendency for PT-INR to increase even more than it did with TC therapy alone.
In the case of initiating TC therapy in patients taking WF, when analgesics or other drugs that are known to have interactions with WF are being given concomitantly, the anticoagulant effect will be increased significantly. Therefore, PT-INR should be closely monitored for a few days after TC therapy and patient education should be conducted before TC therapy is initiated in those on WF.

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We conducted a retrospective assessment of the efficacy and safety of pravastatin sodium in the case of switching from the branded drug to a generic version. The assessment was conducted on 1,337 hyperlipidemic patients at the Kameda General Hospital who had received the branded medicine for more than 28 days before substitution and the generic medicine for more than 28 days after substitution. We investigated the clinical equivalency with regard to efficacy indices including total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride (TG) levels, as well as safety indices including aspartete transferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (γ-GTP), creatine phosphokinase (CPK), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total-bilirubin (T-Bil), blood urea nitrogen (BUN), and serum creatinine (Scr) levels. There were no significant differences in the efficacy and safety indices between before and after substitution.
In subgroup analyses by glycated hemoglobin (HbA1c) or age there were also no significant differences between before and after substitution in the efficacy and safety indices. Detailed investigations on patients whose safety indices deteriorated to 2 or above (CTCAE v3.0 JCOG) showed that in most cases this was due to temporary changes in medical conditions, surgery, or fever. There were 14 patients who had stopped taking the generic possibly due to adverse events but there was no definite causal relationship between them and the generic. We concluded that the generic version of pravastatin administered in this study had similar efficacy and safety profiles to the branded medicine.

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The Nagasaki University School of Pharmaceutical Sciences has conducted a practical training program in community medicine for its students in the Nagasaki Goto Islands in collaboration with the University’s School of Medicine. The purpose of this program was to provide students with an experience of community medicine in remote rural areas from both the public health and social welfare viewpoints.
In order to evaluate the educational effects of this program, a questionnaire survey targeting 84 fourth-year pharmaceutical students who participated in the 2008 academic year was conducted both before and after the practical training. Responses were obtained from almost all the students and revealed that levels of interest in community medicine in the Goto Islands were significantly higher after the training program than before it. Furthermore, a large number of students expressed great satisfaction with the program. Not only the practical training at clinics in remote rural areas but also the opportunities to give lectures on healthcare to local citizens with medical students were highly evaluated by the pharmaceutical students. Therefore, the practical training in community medicine with medical students in the Goto Islands will be continued, conducting it for sixth-year pharmacy students as part of their advanced education from the 2011 academic year onwards.

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Inventory control of expensive injection drugs is highly important in hospital management, and careful handling of highrisk drugs is required to ensure safety in drug therapy. In this regard, when a hospital determines appropriate content sizes to be adopted in the case of drugs available in many different vial sizes, it is necessary to weigh costs against risk management, especially for anti-cancer drugs since they are not only expensive but also highly hazardous. Therefore, the establishment of an adoption strategy for these drugs is a prerequisite for efficient hospital management and safety of drug therapy.
This study looked at an appropriate drug size adoption strategy for anticancer chemotherapeutics at Asahikawa Medical University based the following approach: 1) determine the motives for increasing or decreasing the number of drugs purchased in multiple vial sizes, 2) examine the expected effects of each motive, 3) determine the greatest effect by evaluation of drug properties, 4) in evaluation obtain score for each property and 5) determine appropriate adoption priority indices. A review of the vial sizes adopted based on this approach showed that it would reduce patient co-payments as well as hospital expenses without compromising safety or operational procedures.
Therefore, an effective drug adoption strategy based on individual drug characteristics and available sizes could achieve greater safety and efficiency in hospital management.

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Falls and fall-related injuries among inpatients are one of the most important concerns in medical safety management and sometimes cause a significant decrease in activities of daily living (ADL). It has been suggested that the adverse reactions of psychotropic drugs related to their sedative-hypnotic, cognitive deficit producing and muscle reaction-related effects are closely associated with falls.
In this study, we examined a relationship between the risk of falls and psychotropic drugs based on prescriptions in fall incident reports at Nagoya University Hospital in a 12-month period beginning in April 1, 2005. In July 2006, we conducted an educational intervention involving instructing health care staff on the optimal use of psychotropics. After doing this, we examined prescriptions in fall incident reports over a 12-month period beginning in April 1, 2006. The results showed a decrease in fall incidence due to long-acting drugs in 2006 as compared with 2005 and this indicated that, among psychotropics, sedativehypnotic-anxiolytics were one of the highest risk factors for falls. These results suggest that an educational intervention can be an effective means of reducing the number of falls and fall-related injuries among inpatients.

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Recent studies carried out in Western countries have suggested a potential adverse interaction between clopidogrel and proton pump inhibitors (PPIs), which inhibit CYP2C19 activity. The purpose of this study was to examine the influence of individual PPIs and CYP2C19 polymorphism on the antiplatelet effect of clopidogrel in Japan. The platelet aggregations induced by 20 μmol/L ADP and CYP2C19 single nucleotide polymorphisms (^*2 and ^*3) were determined in 118 patients on aspirin plus clopidogrel (75 mg/day) therapy. Twenty-five and 13 patients were treated with lansoprazole and rabeprazole, respectively. The platelet aggregation of extensive metabolizers (EM : ^*1/^*1) treated with lansoprazole tended to be higher than those not given a PPI (21.5 % vs. 17.4 %, respectively, p=0.14). Lansoprazole was observed to have no effect on platelet aggregation in intermediate metabolizers (IM : ^*1/^*2 and ^*1/^*3) and poor metabolizers (PM : ^*2/^*2, ^*2/^*3, and ^*3/^*3). Furthermore, platelet aggregation in IMs and PMs not given lansoprazole was significantly higher than that in EMs taking lansoprazole. Rabeprazole did not affect platelet aggregation in any genotype. These results suggest that the influence of PPIs on the antiplatelet effect of clopidogrel is minimal in Japanese patients.

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Liposomal-Amphotericin B (L-AMB) may cause hypokalemia. This study was carried out to examine the occurrence of hypokalemia and its primary causes in 74 patients who were administered L-AMB. They were divided into 2 groups regarding the severity of hypokalemia that occurred: Grade 0-2 group: 35 patients (47.3%), and Grade 3-4 group: 39 patients (52.7%). The results of a comparison of the Grade 0-2 group and Grade 3-4 group showed that causes for the Grade 3-4 group were significantly different from those in the Grade 0-2 group, which were a serum albumin level of more than 2.82 mg/dL at the start of the L-AMB administration (p=0.004, OR: 8.711, 95%CI: 2.273-45.823), and a history of hypokalemia before L-AMB administration (p=0.009, OR: 7.859, 95%CI: 1.844-44.109) in the Grade 3-4 group.
While combination with trimethoprim-sulfamethoxazole resulted in significant avoidance of Grade 3-4 hypokalemia (p=0.019, OR: 0.233, 95%CI: 0.063-0.750), administration of potassium for preventive or maintenance purposes did not affect the occurrence of hypokalemia (p=0.137, p=0.198). However, for 20 patients with an abnormal serum potassium level (Grade 1 and more) at the start of L-AMB administration, our findings suggested that the preventive/maintenance administration of potassium was indeed effective (p=0.011).
It has been proven that L-AMB causes hypokalemia frequently and the primary causes have been clarified. In this regard, it is important to regularly monitor serum potassium levels and adjust them depending on the situation of patients with hypokalemia.

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We conducted a training program to enhance pharmacy students’ awareness of the importance of medicinal education for children as part of the students’ professional training curriculum at a pharmacy school. In this study, we investigated students’ levels of knowledge of medicinal education before entering university to study pharmacy and evaluated the cognitive changes that took place after they undertook the training program as well as their satisfaction with and their opinions of the usefulness of the training. The program consisted of preparing medicinal education materials and conducting a trial class using the materials prepared. A questionnaire was distributed to 111 pharmacy students who participated in the training program in 2009, and the responses in 107 fully completed questionnaires were analyzed.
Twenty-nine out of the 107 evaluable respondents had had some previous experience in the field of medicinal education (27.1%). Before the training program, 25 of these 29 students (86.2%) and 34 of the 78 students who had had no such experience (43.6%) selected “strongly agree” or “agree” as their response to the statement “medicinal education is necessary for children” while after the training, the response rates for these 2 groups were 86.2% and 85.9%, respectively. The training program also enhanced the students’ interest in medicinal education regardless of their previous experience of it. In addition, 100% of the students responded that the training program was “very useful”, “useful”, or “slightly useful” and 95.3% indicated satisfaction with it. These findings suggest that the training program was useful in increasing the students’ awareness of the importance of medicinal education for children.

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