Comparing the Dosing Period in Package Inserts of Antimicrobial Agents Between Japan and the United States.

Introduction: The duration of antimicrobial therapy is a critical evaluation index of antimicrobial stewardship (AS). The inclusion of the dosing period on package inserts provides a strong reason for clinical intervention by pharmacists in cases where physicians prescribe inappropriate dosing periods. This study investigated differences in the description of dosing periods in antimicrobial package inserts between Japan and the U.S. Methods: We conducted a survey comparing differences in the dosing period of oral and injectable antimicrobials approved and marketed in Japan and the U.S. as of May 1, 2021. The Fisher exact test was used to compare the presence or absence of a description of the dosing period on the package insert between these two countries. Results: We evaluated 69 antimicrobial agents, of which 34 were oral; and 35 were injectable agents. In Japan, 20 (29.0%) of the antimicrobials had package inserts stating the dosing periods, compared with 58 (84.1%) in the U.S. (p < 0.001). Conclusions: It was found that the information on the duration of administration was missing from the package insert in Japan compared to the U.S. Lack of information on the duration of administration may lead to long-term administration by the treating physician and also make it difficult for the pharmacist to inquire about the administration. It is expected that the inclusion of scientifically-based dosing periods in all package inserts will promote AS among physicians and pharmacists who are not specialists in infectious disease therapy.

Prevalence of therapeutic drug monitoring and adherence to imatinib in chronic myeloid leukemia in Japan.

OBJECTIVE: The effectiveness of imatinib, a tyrosine kinase inhibitor recommended for the treatment of chronic myeloid leukemia, is associated with high adherence and trough plasma imatinib concentrations of ~ 1,000 ng/mL. However, adherence and therapeutic drug monitoring (TDM) for imatinib have hardly been reported. This study evaluated the prevalence of TDM and adherence to imatinib for chronic myeloid leukemia in Japan. MATERIALS AND METHODS: Monthly insurance claims data for ~ 5.6 million individuals aged 20 - 74 years between June 1, 2005 and December 31, 2017 were studied. Patients with at least one prescription for imatinib were included to calculate adherence and the annual mean prevalence of TDM for imatinib. RESULTS: A total of 498 patients with 9,620 prescriptions of imatinib were included. After 2013, the number of imatinib prescriptions and the number of patients treated with imatinib were over 1,000 and 200, respectively. The mean annual prevalence of TDM for imatinib was 12.2% (95% confidence interval (CI), 8.1 - 16.1%). Antihyperuricemic drugs and steroids increased the likelihood of TDM. The medication possession ratio for assessment of adherence was 93.5% (95% CI: 91.8 - 95.5%). The annual mean prevalence of TDM for imatinib was low, although adherence was high. CONCLUSION: To encourage the measurement of plasma concentrations of imatinib in clinical settings, adding a package insert, a summary of product characteristics, and a patient information leaflet regarding the implementation of TDM is justified and warrants further attention.

Polymethoxyflavonoids tangeretin and nobiletin increase glucose uptake in murine adipocytes.

Tangeretin and nobiletin are polymethoxyflavonoids that are contained in citrus fruits. Polymethoxyflavonoids are reported to have several biological functions including anti-inflammatory, anti-atherogenic, or anti-diabetic effects. However, whether polymethoxyflavonoids directly affect glucose uptake in tissues is not well understood. In the current study, we investigated whether tangeretin and nobiletin affect glucose uptake in insulin target cells such as adipocytes. We observed that treatment with tangeretin or nobiletin significantly increased the uptake of [(3) H]-deoxyglucose in differentiated 3T3-F442A adipocytes in a concentration-dependent manner. Data showed that phosphatidyl inositol 3 kinase, Akt1/2, and the protein kinase A pathways were involved in the increase in glucose uptake induced by polymethoxyflavonoids. These data suggest that the anti-diabetic action of polymethoxyflavonoids is partly exerted via these signaling pathways in insulin target tissues.