The World Health Organization (WHO) recommends antimicrobial use density (AUD) as an indicator for evaluating the amount of antimicrobials used, an index that is now widely employed in many facilities. Defined daily doses (DDD) set by WHO are used for calculating AUD. However, discrepancies have been noted between other countries and Japan in the standard dosage of antimicrobials, which may cause a problem evaluating antimicrobial use with the DDD. Therefore, in this study, we calculated AUD (modified antimicrobial use density: mAUD) with the DDD (modified defined daily dose: mDDD) of our hospital for the carbapenem antimicrobial meropenem (MEPM), mAUD, and resistance rate of Pseudomonas aeruginosa. From 2010 through fiscal year 2016 (ending in March), AUD was 5.9±1.4, 7.0±2.9, 8.2±2.3, 6.8±2.1, 7.3±2.2, 7.0±2.1, and 8.0±3.0 and mAUD was 11.7±2.7, 12.0±4.9, 11.3±3.1, 11.0± 3.4, 11.4±3.5, 11.5±3.5, and 11.2±4.2, respectively. The corresponding resistance rate of P. aeruginosa was 35.1%, 37.9%, 10.0%, 6.0%, 22.6%, 10.6%, and 10.0%. A significant positive correlation was found between mAUD and the resistance rate of Pseudomonas aeruginosa (P < 0.01, r = 0.88). Our results confirm that the mAUD is an effective index for controlling resistance of P. aeruginosa.

Objective: The use of generic drugs is promoted for the purpose of reductions of medical costs and patient’s copayment.  In general, it is thought that clinical effects of the original brand and the generic drugs are equal if they are bioequivalent.  However, it is necessary to inspect their therapeutic equivalence to use the generic drugs securely.  We, therefore, assessed the therapeutic equivalence and pharmacoeconomics by substitution of an original drug (Amaryl®) with a generic drug (Glimepiride [Tanabe]).
Methods: Therapeutic Equivalence: The total variation was calculated by using the HbA1c levels before it switched from Amaryl® to Glimepiride [Tanabe].  The tolerance limits were set as 1/4 of the total variation.  Pharmacoeconomics: The difference of drug prices and the difference of patient’s copayment were calculated.
Results: As the variation of HbA1c levels was within tolerance limits before and after switching from Amaryl® to Glimepiride [Tanabe], we evaluated that their therapeutic effect was equivalent.  The difference of drug prices after switching from the original to the generic one was 4,582.6 yen/year on average (minimum: 949.0 yen, maximum: 12,045.0 yen); the difference of patient’s copayment was 872.5 yen/year on average (minimum: 0 yen, maximum: 3,613.5 yen).  These data show that the use of the generic drugs is effective to reduce medical costs.
Conclusion: For further promoting the use of the generic drugs, we consider it essential to compare the therapeutic equivalence and the safety of the original and the generic drugs in clinical practice.

Objective: Management of low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) is important for patients with type 2 diabetes merger hyperlipidemia. Pemafibrate (PF) has different characteristics from conventional fibrates. In this study, we retrospectively compared the efficacy and safety of PF and bezafibrate (BF) in patients with type 2 diabetes merger hypertriglyceridemia.Methods: Patients who were administered PF (0.2 mg/day) or BF (400 mg/day) for 24 weeks or longer were included. Twenty patients in each group were extracted using propensity score matching (PS). PS was calculated using the patient background (before the start of administration) of PF or BF. We investigated lipid-related parameters (TG, high density lipoprotein cholesterol [HDL-C], and LDL-C) and other laboratory test parameters pre administration and 24 weeks post administration.Results: TG decreased significantly in both groups (p<0.05). However, there were no significant differences between the two groups in the TG treatment target (<150 mg/dL) achievement rate (p =1.00), TG change rate (p=0.84), and TG change amount (p=0.77). In addition, there were no significant changes in HDL-C and LDL-C in both groups. In the PF group, alanine transaminase (ALT) (p< 0.05), alkaline phosphatase (p<0.05) decreased. In the BF group, ALT (p<0.05) and γ-GTP (p<0.05) decreased. Both groups showed improvement in liver function after 24 weeks. eGFR (p<0.05) significantly decreased only BF group. There were no significant changes in renal function, creatine kinase (CK), or hemoglobin A1c (HbA1c) in either group.Conclusion: Our study suggests that there is no difference in the TG lowering effect and safety of PF and BF in type 2 diabetic patients.

We investigated the relationship between renal function assessment based on cystatin C (CsyC) and serum creatinine levels and the status of chemotherapy use in patients with gynecological cancer undergoing paclitaxel and carboplatin therapy. A significant positive correlation was found between estimated glomerular filtration rate from creatinine (eGFRcre) and eGFR from CsyC (eGFRcys) in the 98 patients included in the study. When eGFRcre and eGFRcys values were grouped according to GFR categories in the CKD severity classification, severe cases (eGFRcys < eGFRcre) were of more advanced age (P < 0.05) and had lower albumin levels (P < 0.01) than matched cases. Although no clear relationship was found between renal function assessment and chemotherapy status, the CysC and eGFRcys values tended to be higher and lower, respectively, in patients whose chemotherapy was deferred (P < 0.01 for CysC, P = 0.07 for eGFRcys). These results suggest that eGFRcre-based renal function assessment is overestimated compared with eGFRcys-based assessment in patients with gynecological cancer and may lead to carboplatin overdose or treatment deferral in elderly patients and patients with hypoalbuminemia.

Direct-acting oral anticoagulants (DOAC) were approved for the prevention of cardiogenic embolism in non-valvular atrial fibrillation in recent years. However, the dosage of DOAC has to be reduced in patients with bleeding tendencies where the risk of hemorrhage is high, and dose reduction strategies differ depending on the type of DOAC. Therefore, we examined the dosage regimens of 4 DOACs (dabigatran, rivaroxaban, apixaban, edoxaban). Among 129 patients treated with DOACs, 85 received the standard dosage and 44 received non-standard dosage regimens. Among the non-standard dosage patients, 6 were taking a high dose (dose reduction was desirable) and 38 patients were taking a low dose (low dose is usually desirable). The low dosage group were significantly older and had a significantly lower CHADS2 score than that of the high dosage group. Hemorrhagic events occurred in 2 patients in the standard dosage group and in 3 patients in the low dosage group. Also, a thrombotic event occurred in only 1 patient in the standard dosage group. About 30% of the patients were on low dosage versus standard dosage. In practice, attending physicians tend to reduce the dose to avoid a hemorrhagic event particularly in elderly persons. However, a hemorrhagic event also occurred with low dosage in this survey. The validity and safety of dosages outside the limits of standard dosage have not been reported even though this dosage method is commonly used in clinical practice. Thus, more data should be accumulated from a large-scale cohort study to clarify this.

Objective: The use of generic drugs is promoted to reduce medical costs and copayments. However, tumor agents are expensive and generic drugs are not widelyused. Thus, it is necessaryto evaluate the safetyof generic drugs in more detail. We compared the incidence of adverse events between the original drug (Gemzar®: GEM) and generic drug (Gemcitabine [Sandoz]: GE-GEM) using propensityscore (PS) matching.Methods: We investigated adverse events in patients who received one course of GEM or GE-GEM. The patient background (age,sex, BSA, cancer type, stage, metastasis, surgical history, and radiotherapy) and administration status (administration route and RDI) were used to calculate the PS.Results: Among all patients (GEM: 51, GE-GEM: 54), a significantlygreater number in the GE-GEM group had cancer metastasis. On comparison of adverse events, there were significantlymore cases of vascular pain (p＜0.05) in the GEM group, and manycases of nausea (p＝0.08) and rash (p＝0.08). Fortypatients in each group were extracted byPS matching. There were no significant differences in the patient background between the groups, and on comparison of adverse events, the two groups did not significantly differ.Conclusion: Our studysuggested that there is no difference in side effects between Gemzar® and gemcitabine [Sandoz]. To compare the incidence of adverse events, it is useful to use PS matching in clinical practice.