The educational program for newly graduated pharmacists in the Department of Pharmacy, Hokkaido University Hospital was revised in 2011. To ensure the appropriateness and safety of drug treatment, an education program for newly graduated pharmacists for the purpose of learning ward-based pharmacy services was developed and a method for evaluating the usefulness of the program was proposed. The program was carried out for new pharmacists in 2013, and the usefulness and objectivity of the program were evaluated. In the program, the new pharmacists received training in central duties as well as seminars for developing problem-solving capabilities in basic duties, TDM seminars and other training. Assessment of the program was carried out every 2 weeks on the basis of evaluation check lists for pharmacy services compiled by the staff in charge, and the progress made in acquiring skills for performing duties was quantified and discussed at regular meetings of the staff in charge. One instructor was assigned to each new pharmacist, and interviews were conducted by the instructor to assess the pharmacist's capabilities for duties and problems including mental aspects. Based on the results of assessments, 3 of 17 new pharmacists had been assigned to ward duties in 2013. Thus, consideration should be given to the assessment period for some parts of the training. The education program for newly graduated pharmacists is therefore considered to be useful for training new pharmacists, and the establishment of indices for objective evaluation is expected to contribute greatly to the enhancement of capabilities to perform duties.

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The simple suspension method (SSM) is a method of administering drugs via feeding or gastrostomy tubes to those who have difficulty swallowing. In the SSM, solid formulations (eg, tablets, capsules) are immersed in hot (55℃) water. This promotes the disintegration and dissolution of the drugs and changes their solubility. However, pharmaceutical companies have not issued test results on the solubility and dissolution behaviors of suspended drugs prepared according to the SSM.
For this study, we chose 10 drugs, 8 listed and 2 not listed in the Japanese Orange Book, to compare the dissolution behaviors of each drug, treated vs untreated with the SSM. Dissolution was classified into three patterns: rapid (gliclazide and famotidine), moderate (propranolol, pindolol, metoprolol), and slow (furosemide, ibuprofen, glimepiride). The initial dissolution rates of the moderate-dissolution drugs increased markedly by employing the SSM. In this study, hydroxyzine capsules and phenytoin tablets, neither of which is listed in the Japanese Orange Book, were compared with different dosage/administration forms of those drugs listed in the book (ie hydroxyzine tablets and phenytoinphenobarbital combination tablets). The dissolution behavior of these drugs was not estimated from the dissolution profiles of different forms available in the book. Nevertheless, it seemed that the available data on the dissolution of drugs will be useful when pharmacists estimate the dissolution behavior of drugs administered using the SSM.

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The anti-tumor agent gemcitabine hydrochloride is stable in solid state; however, deamination occurs in acidic solution, yielding β-uridine analogue, whereas anomerization reaction occurs in basic solution. Thus, the brand-name preparation for injection is supplied as lyophilized dry powder, and ingredients are added to result in acidic solution when dissolved in saline. In this study, a brand- and 6 generic-name medicines were compared with regard to gemcitabine stability, β-uridine production, and pH during storage at 25℃ for 6 months after dissolving in saline. Gemcitabine concentrations were decreased time-dependently, and β-uridine concentrations were increased. The pH values were constant. Another generic medicine supplied as solution was also subjected for comparison. At the start of the experiments (Time 0), β-uridine had already been produced in the generic medicine supplied as solution. These results suggest that the generic medicine supplied as solution has to be maintained for tight control in the processes of manufacturing or distribution.

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Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs) are classified as renin-angiotensin system blockers. Angioedema is a serious adverse event caused by ACEIs. There have been fewer reports of angioedema associated with ARBs than with ACEIs. The Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) are widely used for pharmacovigilance. We analyzed the association of renin-angiotensin system blockers and angioedema in reports of the FAERS and JADER database, and classified type of ACEIs and ARBs in Weibull distribution. Reports for 13 ACEIs (lisinopril, ramipril, etc) and 7 ARBs (valsartan, losartan, etc) were analyzed. We evaluated the association between each drug and adverse event using the number of relevant reports, reporting ratio, and reporting odds ratio (ROR). FAERS contained 4,746,890 reports, and after excluding duplicate data, 3,522,995 reports were analyzed. The number of reports relating to angioedema was 215,569. The ROR of ACEIs and ARBs associated with angioedema was 2.3 (95% confidence interval [CI]: 2.3-2.3) and 1.8 (95% CI: 1.8-1.8), respectively. JADER contained 292,720 reports. The number of reports relating to angioedema was 6,764. The ROR of ACEIs and ARBs associated with angioedema was 1.5 (95%CI: 1.3-1.7) and 1.0 (95%CI: 1.0-1.1), respectively. The RORs indicate that angioedema is positively associated with both ACEIs and ARBs. ACEIs and ARBs are classified as early failure type in Weibull distribution. ACEIs and ARBs should be administered carefully with regard to angioedema.

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Erlotinib and gefitinib are oral molecular target drugs for treating non-small cell lung cancer. To provide effective treatment and prevent severe toxicities, it is crucial to educate patients regarding the proper usage and adverse reactions of these drugs. Pharmacists play a key role in this respect. As there are no established patient education tools or tests for measuring patient understanding of molecular target drugs, each pharmacist evaluates the depth of patient understanding depending on their experience. In the present study, we developed various support tools such as understanding check sheet, medicine instruction sheet, leaflet of drug interaction with citrus fruits, and rash management manuals to standardize the patient education method. Each patient was tested twice with the understanding check sheet. Firstly, just after the physician/nurse explained the treatment; secondly, immediately before discharge. After the first test, we explained to the patients the questions they had answered incorrectly, with the help of the tools described above. To evaluate the usefulness of these tools, the percentage answered correctly in the understanding check sheet before and after the education was compared in 39 patients treated with erlotinib or gefitinib. The percentage answered correctly increased significantly after the education. These results suggest that the patient education system using education support tools is useful to improve patient understanding regarding erlotinib and gefitinib.

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Denosumab was shown to be superior to zoledronic acid for the prevention of skeletal-related events in advanced cancer patients with bone metastasis. However, hypocalcemia has been reported as a serious adverse effect after the administration of denosumab. Various risk factors associated with hypocalcemia induced by denosumab have not yet been clarified. To clarify the risk factors associated with hypocalcemia induced by denosumab, we retrospectively reviewed the records of 57 patients who had received denosumab at Yamato Municipal Hospital between May 2012 and April 2014. They were divided into hypocalcemia (n = 13) and non-hypocalcemia (n = 44) groups according to the serum calcium level. A comparison of the patient backgrounds in the two groups revealed significant differences in the breast cancer and administration of proton pump inhibitors (PPIs). Multiple logistic regression analysis showed that the administration of PPIs (odds ratio: 7.59, 95% confidence interval: 1.30-44.42, P = 0.025) was significantly related to hypocalcemia induced by denosumab. Therefore, the administration of PPIs may be the principal cause of development in hypocalcemia induced by denosumab and they should be used with caution.

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Cancer chemotherapy for uric acid degrading enzyme preparation Rasburicase is an effective drug as a treatment and prophylactic for tumor lysis syndrome (TLS). It exerts a rapid uric acid reduction effect by its powerful uric acid oxidation action. Details such as uric acids and electrolytes after completion of the drug administration have not been studied, though re-rise of the uric acid, and uric acid levels have not been reported as risk factors for re-increase. In this study, adult hematologic malignancies patients treated with Rasburicase for TLS prophylactic purposes after cancer chemotherapy were classified into a drug increment of uric acid group and no increment of uric acid group. We investigated the risk factors for increment of uric acid and examined the daily dose of Rasburicase, administration period, TLS risk classification, serum phosphorus, potassium, calcium values before administration. There was a significant difference between the two groups, and the multiple logistic regression analysis showed that the daily dosage and administration period of Rasburicase were significant. These results indicate that the dosage and administration period should be carefully considered when re-administering Rasburicase.

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We report the cases of 10 patients with acute lithium intoxication who were treated over the past 6 years. The range of lithium overdose was 600 mg to 9,600 mg and the lithium concentration of all cases was greater than the toxic concentration. Three of the 10 cases were treated with fluid therapy. Another 3 cases were treated with continuous hemodiafiltration (CHDF). The rest were treated with hemodialysis (HD). The serum lithium concentration of the 3 patients with fluid therapy gradually decreased. However, it took 24 hours after the treatment to reach the therapeutic level in Case 2 since the slope was comparatively loose. In the meantime, the high lithium concentration of patients with CHDF (Cases 4, 8, 10) and HD rapidly decreased and it finally reached the therapeutic level. But a post-dialysis rebound effect in the lithium concentration was detected in Case 9. This report shows that CHDF and HD is an effective and sufficient treatment for lowering the serum concentration of lithium in a short period in acute lithium toxicity. As the serum lithium concentration of a patient with HD often rebounds and repeated or prolonged treatment may be required, we reaffirmed the patient's condition. Thus, completion of HD should be judged based on not only serum lithium concentration but also sufficient observation of the clinical course.

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