Because neutropenia involves susceptibility to severe infection, appropriate management of neutropenia is required during cancer chemotherapy. Assessing individual patients’ background to identify those at high risk is an important step. A systematic review of the literature was performed to overview recent findings about neutropenia risk factors. Type of cancer, treatment regimen, patient age, gender, performance status, comorbidities, laboratory abnormalities, prior therapies and some genetic polymorphisms were reported as risk factors for neutropenic complications.
We have reported novel findings on the risk factor of severe neutropenia by using a pharmacoepidemiologic approach. One of them clarifies the increased risk by drug-drug interaction between vinorelbine and clarithromycin. Patients who were administered clarithromycin during chemotherapy with vinorelbine were at 4.52-times higher risk for severe neutropenia compared with patients who were administered vinorelbine alone. Another study reveals ethnic diversity in docetaxel toxicity between Asian and non-Asian clinical studies using integrated analysis of published articles. Clinical trials conducted in Asia had 19.0 times higher risk on severe neutropenia compared with non-Asian trials. Pharmacists and clinicians should mention such ethnic diversity.
Like our studies, a pharmacoepidemiologic approach is useful for the clinical pharmacists’ study that aims to identify risk factors on pharmacotherapy.

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Pharmacists need to check prescriptions of parenteral lipid emulsions from various aspects due to the many difficulties that occur when administering them. Thus, we performed a questionnaire survey on the usage of and current involvement of pharmacists in administering parenteral lipid emulsions. Pharmaceutical departments of 381 institutions in Osaka Prefecture participated in this survey between June 1 and July 31, 2012. The questionnaire contained items including the characteristics of the hospital, usage of parenteral lipid emulsions, and current prescription-checking by pharmacists. A hundred and twelve institutions (29.4%) responded to the survey; parenteral lipid emulsions were used in 96 institutions. Some institutions appropriately used them but others did not. Additionally, in some institutions, pharmacists did not check the prescriptions for detailed items, such as the dosing rate and administration route. Furthermore, we observed a trend toward more items indicating the inappropriate use of these emulsions and less involvement of pharmacists in institutions without compared to with a nutrition support team (NST). These current situations were considered to largely relate to the number of pharmacists and whether NST therapists (pharmacists) are available. In the future, pharmacists should significantly contribute to nutritional and risk management in in-hospital team medicine.

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The inhalation profile (flow rate, volume and pattern) from a dry powder inhaler (DPI) is crucial for the efficient delivery of medications to the bronchial airways. However, instructions regarding the inhalation profile are not always adequate. We recruited 28 volunteers who were not familiar with DPIs to simulate patients who received the first prescription of a DPI. Following verbal instructions, they inhaled from various DPIs, and we recorded the inhalation profiles as listed above. Flow-time curves were classified into 3 patterns. A: early peak followed by a linear decrement, C: trapezoid, B: between A and C. Mean ( ± SD) peak inhaled flow rates (PIFR) and volumes were 54.3 ± 23.5 L・min^-1and 1.40 ± 0.58 L for the Diskus^®, 52.8 ± 11.5 and 1.39 ± 0.58 for the Turbuhaler^®, and 46.0 ± 13.4 and 1.27 ± 0.74 for the Twisthaler^®, respectively. There were weak correlations between PIFRs and inhalation volumes. Percent of subjects attaining a PIFR > 30 L・min^-1 was 92.9% (Diskus^®), 92.9% (Turbuhaler^®), and 100% (Twisthaler^®), and those attaining a PIFR > 60 L・min^-1 were 32.2% (Diskus^®), 17.9% (Turbuhaler^®), and 14.3% (Twisthaler^®). Only a few subjects inhaled with pattern A, and most of the subjects inhaled with pattern C. In conclusion, untrained patients may inhale with suboptimal flow rates and volumes from a DPI. Inhaled flow patterns may also be poor.

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Onco-Tain^TM Vial, which was developed to prevent occupational exposures to hazardous drugs such as antineoplastic drugs, is a vial preparation equipped with sheathings (a PVC reinforced base and a shrink wrapping of a protective PET sleeve on the vial). The shatter-resistance of the Onco-Tain™ vial was evaluated with a free fall test. Four types (9 strengths in total) of Onco-Tain™ vials, which contain antineoplastic agents and are available worldwide, were used in the test. Vials with the PVC bases and PET sleeves removed from the Onco-Tain™ vial were used as the control. Mimicking the fall of vials in the medical setting, the falling heights were set at 70, 135 and 180 cm, and the breakage ratios of vials and the scattering area of contents were measured.
In the control group (Non-OT group), 3.5, 9.4 and 8.9 percent of vials were broken at the heights of 70, 135 and 180 cm, respectively, and the scattering of contents was observed in all broken vials. The breakage ratios of vials in the Onco-Tain™ vial group (OT group) were statistically significantly lower (0.0 and 2.4%) at the heights of 70 and 135 cm, and tended to be lower (3.3%) at the height of 180 cm. No leakage was observed in vials broken in the OT group. The significant improvement of shatter-resistance of vials was confirmed by applying the protection sleeves to the surface of the vials. By applying these concepts in the future, a decrease of occupational exposures to hazardous drugs caused by the breakage of containers is expected.

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Among the adverse effects of anticancer drugs, critical effects have attracted the most attention. However, non-critical adverse effects that lower the quality of life of cancer patients have been gaining recognition. For example, the package insert of tegafur･gimeracil･oteracil potassium (S-1) was modified and lacrimal duct obstruction was added to the list of critical adverse effects on September 25, 2012. In a similar vein, this study aimed to examine the awareness of healthcare professionals regarding the adverse effects of anticancer drugs on the eyes. A web-based questionnaire survey was administered to medical doctors and pharmacists. We received responses from 38 doctors and 123 pharmacists. Only 39.5% (15) of the doctors and 33.3% (41) of the pharmacists were aware of the adverse effects of anticancer drugs on the eyes. Among respondents who had observed these adverse effects, only 12.5% (1/8) of doctors and 11.1% (2/18) of pharmacists reported them to the authorities or the pharmaceutical companies. The results suggest that the adverse effects of anticancer drugs on the eyes should gain more recognition among healthcare professionals. Therefore, we would like to encourage them in obtaining information concerning the safety of medicines and to report all observed adverse effects regardless of their severity.

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Recent studies have reported methotrexate (MTX) delayed excretion in the case of co-administration of proton pump inhibitor (PPI) in high-dose MTX therapy. We investigated whether PPI influenced the serum concentration of MTX (MTX-con) in intermediate-dose MTX chemotherapy. We also investigated the relation between MTX-con and blood urea nitrogen (BUN) / serum creatinine (SCr) ratio before the treatment, which is a kind of laboratory indicator of dehydration. MTX-con and SCr increase after the treatment. We examined MTX-con for 36 cycles in 19 candidates in our institution. Co-administration of PPI was observed in 8/36 (22%). Average MTX-con at 48 hr after MTX administration with and without co-administration of PPI was 0.32 ± 0.12 μM and 0.41 ± 0.37 μM respectively (P = 0.92). A BUN/SCr ratio indication over 20 before therapy was observed in 10/36 (28%). Average MTX-con at 48 hr after MTX administration was 0.21 ± 0.14 μM in the BUN/SCr ratio 20 and over group, 0.46 ± 0.36 μM in the BUN/SCr ratio under 20 group (P < 0.01). SCr increased over 0.3 mg/dL after MTX administration was observed in 4/36 (11%). Average MTX-con after 48 hr MTX administration was 0.72 ± 0.6 μM in the SCr 0.3 and over group, 0.35 ± 0.27 μM in the SCr under 0.3 mg/dL group (P < 0.05). Co-administration of PPI is not associated with MTX delayed excretion and BUN/SCr ratio before the treatment and SCr increase after the treatment was suggested as a possible factor in MTX-con influence.

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