Language：Japanese   Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Although remdesivir, a prodrug of nucleoside analog (GS‐441524), has demonstrated clinical benefits in coronavirus disease 2019 (COVID‐19) treatment, its pharmacokinetics (PKs) in patients with COVID‐19 remain poorly understood. Therefore, in this study, the PKs of remdesivir and its major metabolite, GS‐441524, were evaluated using a population PK (PopPK) approach to understand the PK aspect and exposure–clinical outcome relationship. The serum concentrations of remdesivir and GS‐441524 (102 points in 39 patients) were measured using liquid chromatography–tandem mass spectrometry. All patients received 200 mg remdesivir on the first day, followed by 100 mg on 2–5 days, except for one patient who discontinued remdesivir on day 4. The median (range) age, body surface area, and estimated glomerular filtration rate (eGFR) were 70 (42–85), 1.74 m² (1.36–2.03), and 68 mL/min/1.73 m² (33–113), respectively. A compartment model with first‐order elimination combined with remdesivir and GS‐441524 was used for nonlinear mixed‐effects model analysis. Remdesivir was rapidly eliminated after infusion, whereas GS‐441524 was eliminated relatively slowly (half‐time = 17.1 h). The estimated apparent clearance (CL) and distribution volume of GS‐441524 were 11.0 L/h (intersubject variability [ISV]% = 43.0%) and 271 L (ISV% = 58.1%), respectively. The CL of GS‐441524 was significantly related to the eGFR (CL × [eGFR/68]^0.745). The post hoc area under the curve of GS‐441524 was unrelated to the recovery rate or aspartate aminotransferase/alanine aminotransferase elevation. Overall, PopPK analysis showed the rapid elimination of remdesivir in the blood, and GS‐441524 accumulation depended on eGFR in patients with COVID‐19. However, no relevance of exposure–clinical outcome was not suggestive of the dose adjustment of remdesivir.

DOI： 10.1002/psp4.12936

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/psp4.12936

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although automated dispensing robots have been implemented for medication dispensing in Japan, their effect is yet to be fully investigated. In this study, we evaluated the effect of automated dispensing robots and collaborative work with pharmacy support staff on medication dispensing. METHODS: A robotic dispensing system integrating the following three components was established: (1) automated dispensing robot (Drug Station®), which is operated by pharmacy support staff, (2) automated dispensing robot for powdered medicine (Mini DimeRo®), and (3) bar-coded medication dispensing support system with personal digital assistance (Hp-PORIMS®). Subsequently, we evaluated the incidences of dispensing errors and dispensing times before and after introducing the robotic dispensing system. Dispensing errors were classified into two categories, namely prevented dispensing errors and unprevented dispensing errors. The incidence of dispensing errors was calculated as follows: incidence of dispensing errors = total number of dispensing errors/total number of medication orders in each prescription. RESULTS: After introducing the robotic dispensing system, the total incidence of prevented dispensing errors was significantly reduced (0.204% [324/158,548] to 0.044% [50/114,111], p < 0.001). The total incidence of unprevented dispensing errors was significantly reduced (0.015% [24/158,548] to 0.002% [2/114,111], p < 0.001). The number of cases of wrong strength and wrong drug, which can seriously impact a patient's health, reduced to almost zero. The median dispensing time of pharmacists per prescription was significantly reduced (from 60 to 23 s, p < 0.001). CONCLUSIONS: The robotic dispensing system enabled the process of medication dispensing by pharmacist to be partially and safely shared with automated dispensing robots and pharmacy support staff. Therefore, clinical care for patients by pharmacists could be enhanced by ensuring quality and safety of medication.

DOI： 10.1186/s40780-022-00255-w

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Medication-related osteonecrosis of the jaw is a serious adverse event associated with bone-modifying agents, such as injectable bisphosphonate (zoledronic acid) and the anti-receptor activator of nuclear factor-κB ligand antibody (denosumab). OBJECTIVE: This study aims to evaluate and compare the time-to-onset profile for medication-related osteonecrosis of the jaw associated with denosumab between treatment-naïve (naïve group) and pre-treatment with zoledronic acid (post-zoledronic acid group) patients using the Japanese Adverse Drug Event Report database. METHODS: Medication-related osteonecrosis of the jaw was defined according to the Medical Dictionary for Regulatory Activities. The medication-related osteonecrosis of the jaw onset profiles were evaluated using the Weibull shape parameter and the log-rank test. RESULTS: The Japanese Adverse Drug Event Report database contains 632,409 reports published between April 2004 and March 2020. In the time-to-onset analysis, after extracting the combinations with complete information for the treatment start date and the medication-related osteonecrosis of the jaw onset date, 272 reports of the naïve group and 86 reports of the post-zoledronic acid group were analyzed. The median onset in the naïve and post-zoledronic acid groups was 487.0 (25-75%: 274.0-690.8) and 305.5 (25-75%: 158.3-508.5) days, respectively. Medication-related osteonecrosis of the jaw occurred earlier in the post-zoledronic acid group than in the naïve group, and the log-rank test demonstrated a significant difference in their time transitions (p < 0.0001). CONCLUSIONS: The results indicated a risk of medication-related osteonecrosis of the jaw in naïve and post-zoledronic acid groups and a shorter onset time in the latter than in the former. Thus, healthcare professionals should take the early risk of medication-related osteonecrosis of the jaw into account when switching patients from zoledronic acid to denosumab treatment.

DOI： 10.1007/s40801-022-00324-4

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Nivolumab is an anti-programmed death-1 (PD-1) antibody used for immuno-oncological therapy of various cancers, including non-small cell lung cancer (NSCLC). This study aimed to characterize the real-world population pharmacokinetics (PK) of nivolumab in NSCLC patients. METHODS: PK samples were collected by opportunistic sampling of Japanese NSCLC patients treated with nivolumab monotherapy. Population PK analysis was performed using a two-compartment model in NONMEM. Patient-specific factors such as body weight, age, sex, serum albumin (ALB), estimated glomerular filtration rate (eGFR), performance status, programmed cell death receptor ligand 1 (PD-L1) expression in tumors, and treatment periods were evaluated as potential covariates for clearance. RESULTS: A total of 223 serum samples collected from 34 patients were available for analysis. The median (min-max) age and weight were 69 years (38-83) and 62.7 kg (36.8-80.5), respectively. The mean (95 % confidence interval) clearance estimate was 0.0064 L/h (0.0058-0.0070). The inclusion of the ALB level, eGFR, and treatment period significantly improved the model fit. CONCLUSION: A real-world nivolumab population PK model was developed using an opportunistic sampling strategy in Japanese patients with NSCLC. Further studies are warranted to characterize the exposure-response relationship and determine the optimal dosing regimens for these patients.

DOI： 10.1097/FTD.0000000000000996

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Purpose

Patients receiving vascular endothelial growth factor–tyrosine kinase inhibitors are at a risk of developing proteinuria. Renin–angiotensin system (RAS) inhibitors exert renoprotective effects and might reduce proteinuria risk in these patients. We investigated the risk factors for and protective effect of RAS inhibitors against proteinuria in patients with renal cell carcinoma (RCC) receiving axitinib.

Methods

We retrospectively reviewed the medical records of patients with RCC receiving axitinib at Kobe City Medical Center General Hospital between September 2012 and October 2020. Patients with proteinuria ≥ 2+ at baseline were excluded. The patients were categorized into RAS inhibitor user, non-RAS inhibitor user, and non-user groups. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events, version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors for developing grade ≥ 2 proteinuria.

Results

Among 42 patients, 28 received antihypertensive drugs at baseline. Among these, 17 and 11 patients were in the RAS inhibitor and non-RAS inhibitor user groups, respectively. Twenty-three patients (54.8%) developed grade ≥ 2 proteinuria. The multivariate analysis revealed that the non-RAS inhibitor user group (P = 0.001) and patients with pre-existing grade 1 proteinuria (P = 0.022) were significantly associated with the development of grade ≥ 2 proteinuria, whereas the RAS inhibitor user group was not significantly associated with it.

Conclusion

In patients with RCC receiving axitinib, pre-existing proteinuria and non-RAS inhibitor use were significantly associated with grade ≥ 2 proteinuria development. Our preliminary data should be confirmed by further studies.

DOI： 10.1007/s00280-022-04408-4

Other Link： https://link.springer.com/article/10.1007/s00280-022-04408-4/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Despite reports on the impact of vitamin D status on coronavirus disease 2019 (COVID-19) severity, the association between low vitamin D status and severe COVID-19 remains unclear. Moreover, researchers have not determined the aforementioned association in Japanese patients. This study aimed to investigate the association between 25-hydroxyvitamin D [25(OH)D] levels and COVID-19 severity in Japanese patients. METHODS: This retrospective observational study included 117 consecutive patients with COVID-19 admitted to the Kobe City Medical Center General Hospital between October 01, 2020, and January 31, 2021. We measured the serum 25(OH)D levels using blood specimens collected within 5 days of hospital admission using liquid chromatography-tandem mass spectrometry. RESULTS: There were 21 (17.9%), 73 (62.4%), 19 (16.2%) and 4 (3.4%) patients with severe deficiency (<10 ng/mL), deficiency (10-<20 ng/mL), insufficiency (20-<30 ng/mL), and sufficiency (≥30 ng/mL) of vitamin D, respectively. In univariate logistic regression analyses, lower serum 25(OH)D levels [odds ratio (OR) 1.18 per 1 ng/mL decrease, 95% confidence interval (CI) 1.04-1.33, p = 0.007] were significantly associated with invasive mechanical ventilation (IMV) or death. In a multivariate logistic regression analysis, low serum 25(OH)D levels [OR 1.22 per 1 ng/mL decrease, 95% CI 1.06-1.40, p = 0.005] were significantly associated with IMV or death. The cut-off value of serum 25(OH)D levels was 10.4 ng/mL, calculated by the receiver operating characteristic curve to detect the requirement for IMV or death. CONCLUSIONS: To the best of our knowledge, this is the first study to assess the association between vitamin D status and COVID-19 severity in Japanese patients. Low serum 25(OH)D level was detected as an independent risk factor for severe COVID-19 among Japanese patients.

DOI： 10.1016/j.clnesp.2022.04.003

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

DOI： 10.1248/bpb.b21-00913

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis. METHODS: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups. RESULTS: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65-5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38-7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17-5.01; p = 0.016). CONCLUSION: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

DOI： 10.1007/s00520-021-06634-7

PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Background: Enzalutamide is useful for the treatment of castration-resistant prostate cancer (CRPC). Despite its usefulness, adverse events (AEs) sometimes force patients to discontinue treatment. To maximize patient care, we developed an ambulatory care pharmacy practice that allows collaboration between a pharmacist and urologist to manage patients with CRPC receiving enzalutamide. In this study, we investigated the efficacy of this collaborative management. Methods: A retrospective chart review of 103 patients with CRPC receiving enzalutamide in our hospital between May 2014 and December 2020 was performed. Our collaborative management was implemented in October 2016. Before being examined by urologists, patients visited the oncology pharmacy consultation room for a face-to-face consultation, wherein the oncology pharmacists assessed factors such as adherence to enzalutamide, any AEs and their grades, and provided their suggestions to the urologists. The time to enzalutamide discontinuation and prostate-specific antigen progression were compared between patients who started enzalutamide before (n = 41) and after (n = 62) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with enzalutamide discontinuation. Results: After implementing collaborative management, the pharmacists had 881 patient consultations. Among the 476 suggestions from pharmacists, 345 were accepted by urologists. The most frequent suggestion was supportive care in enzalutamide treatment (224 suggestions). Multivariate analysis showed that collaborative management [hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.31-0.89, p = 0.017] and higher prostate-specific antigen (PSA; HR 2.41, 95% CI 1.36-4.28, p = 0.003) were significantly associated with enzalutamide discontinuation. The median time to discontinuation (18.9 vs. 7.6 months, p = 0.012), time to discontinuation due to AEs (not reached in both groups, p = 0.001), and time to PSA progression (13.3 vs. 5.8 months, p = 0.002) were all significantly longer in the after group. Conclusions: We implemented a pharmacist-urologist collaborative management program for outpatients with CRPC receiving enzalutamide. The results revealed that collaborative management was useful for prolonging the time to enzalutamide discontinuation.

DOI： 10.3389/fphar.2022.901099

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The antiretroviral drug favipiravir inhibits RNA-dependent RNA polymerase. It has been developed for the treatment of novel coronavirus (SARS-CoV-2) infection disease (COVID-19). However, its pharmacokinetics in patients with COVID-19 is poorly understood. In this study, we measured favipiravir serum concentration by liquid chromatography-tandem mass spectrometry and conducted population pharmacokinetic (PPK) analysis. Thirty-nine patients were enrolled in the study: 33 were administered FPV 1600 mg twice-daily (BID) on the first day followed by 600 mg BID, and 6 were administered FPV 1800 mg BID on the first day followed by 800 mg or 600 mg BID. The median age was 68 years (range, 27-89 years), males were 31 (79.5%), median body surface area (BSA) was 1.72 m² (range, 1.11-2.2), and patients requiring invasive mechanical ventilation (IMV) at the start of favipiravir was 10 (25.6%). Two-hundred and four serum concentrations were available for pharmacokinetic analysis. A one-compartment model with first-order elimination was used to describe the pharmacokinetics. The estimated mean clearance/bioavailability (CL/F) and distribution volume/bioavailability (V/F) were 5.11 L/h and 41.6 L, respectively. Covariate analysis revealed that CL/F was significantly related to dosage, IMV use, and BSA. Simulation study showed that the 1600 mg/600 mg BID regimen was insufficient for the treatment of COVID-19 targeting EC50 (9.7µg/mL), especially in patients with larger BSA and/or IMV. A higher favipiravir dosage is required for COVID-19, but dose-dependent nonlinear pharmacokinetics may cause an unexpected significant pharmacokinetic change and drug toxicity. Further studies are warranted to explore the optimal favipiravir regimen.

DOI： 10.1002/psp4.12685

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

<h4>Background</h4>Pneumocystis pneumonia (PCP) is a potentially life-threatening infection. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered as the first regimen for PCP prophylaxis according to several guidelines. The recommended prophylactic dose of TMP-SMX has been determined based on patients with normal renal function, but the appropriate dosage for patients undergoing hemodialysis is unknown. The aim of this study was to investigate the efficacy and safety of low-dose TMP-SMX in patients undergoing hemodialysis.<h4>Methods</h4>HIV-uninfected adult patients who were undergoing hemodialysis and administered TMP-SMX for PCP prophylaxis, were included, and divided into standard-dose (≥6 single strength (SS, TMP-SMX 80 mg/400 mg tablets/week) and low-dose groups (< 6 SS tablets/week). The endpoints were cumulative incidence of PCP and cumulative discontinuation rate of TMP-SMX due to adverse events. For comparison of the groups, we employed the chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables. Risk factors for the endpoints were evaluated using the Cox Fine and Gray method.<h4>Results</h4>The median age of the 81 patients included in the study was 67 years (IQR: 60-76 years), and 52 patients (64.2%) were men. No patients in either group developed PCP during the observation period. The yearly cumulative incidence of discontinuation was 12.1% (95% confidence interval [CI]: 0.027-0.29) in the low-dose group and 35.6% (95% CI: 0.20-0.52) in the standard-dose group (P = 0.019). The adjusted hazard ratio of the low-dose group compared to standard-dose group was 0.18 (95% CI: 0.04-0.86, P = 0.032).<h4>Conclusions</h4>None of the study patients developed PCP, and the cumulative discontinuation rate of TMP-SMX due to adverse events was significantly lower in the low-dose group compared to that in the standard-dose group (P = 0.032). These results indicate that low-dose TMP-SMX is an appropriate regimen to maintain a balance between PCP prophylaxis and prevention of adverse events due to TMP-SMX administration. These findings can guide health care professionals to determine TMP-SMX dosage when considering PCP prophylaxis for patients undergoing hemodialysis.

DOI： 10.1186/s12879-021-06374-3

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event associated with several antineoplastic drugs; however, the precise risks and time course of reactions of particular drugs are not clearly understood. The aim of this study was to evaluate the relationship between anticancer agents and CIPN development using data from the Japanese Adverse Drug Event Report (JADER) database and to characterize the time-to-onset and outcomes of CIPN. Chemotherapy-induced peripheral neuropathy was defined using the Medical Dictionary for Regulatory Activities preferred terms. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence interval for signal detection. Data of nine Anatomical Therapeutic Chemical (ATC) drug categories correlated with CIPN development, in addition to the data of the time-to-onset and outcomes. Among 622,289 reports in the JADER database from April 2004 to March 2020, there were 1883 reports of adverse events corresponding to peripheral neuropathy. The ROR (95% confidence interval) for vinblastine, sorbent-based paclitaxel (sb-PTX), oxaliplatin, and bortezomib was 20.4 (12.5-33.4), 13.6 (11.9-15.7), 26.2 (23.6-29.1), and 30.8 (26.6-35.8), respectively. The median duration (interquartile range) to CIPN development after the administration of vinca alkaloids and analogues, taxanes, platinum compounds, and monoclonal antibodies was 11.0 (5.0-46.5), 22.5 (6.0-82.5), 22.0 (6.0-68.5), and 32.5 (11.3-73.8) days, respectively. The median duration (interquartile range) of sb-PTX and nanoparticle albumin-bound (nab)-PTX was 35.0 (7.0-94.0) and 5.5 (3.0-29.3) days, respectively. Our analysis of records in the JADER database revealed several drugs associated with a high risk for CIPN development. In particular, the development of CIPN after vinca alkaloid administration should be closely monitored for 2 weeks after administration. CIPN caused by nab-PTX showed significantly faster onset than that by sb-PTX. Patients who receive taxanes or monoclonal antibodies often do not show an improvement; accordingly, early treatment is required.

DOI： 10.1038/s41598-021-90848-6

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

<h4>Background</h4>Primary angle closure disease (PACD) is a type of glaucoma in which the intraocular pressure (IOP) is increased because of the blockage of the anterior chamber angle. Medications contraindicated for patients with PACD, such as anticholinergics, cause mydriasis, and can elevate IOP. However, anticholinergics are currently contraindicated only for primary angle closure glaucoma (PACG) in Japanese package inserts. In this study, we investigated the prescription status of medications contraindicated for PACD, such as anticholinergics, in patients with PACD scheduled for eye surgeries.<h4>Methods</h4>Forty-three Japanese patients diagnosed with PACD at Kobe City Eye Hospital, Japan, and scheduled hospitalization for eye surgeries between December 2017 and July 2018, were included. Data, including sex, age, diagnosis, IOP, anterior chamber depth, and patients' regular medications prior to hospitalization, were collected for each patient from the electronic medical records.<h4>Results</h4>The number of patients with chronic primary angle closure (CPAC) and acute primary angle closure (APAC) was 35 (81.4%) and 8 (18.6%), respectively. Among all the 43 patients with PACD, 8 (18.6%) received 15 medications that are potentially contraindicated for PACD by non-ophthalmologist. According to medication categories, benzodiazepine hypnotics were the most commonly prescribed. Among the 8 patients with APAC, 2 (25.0%) had routinely received medications contraindicated for PACD. The median number of all kinds of prescriptions on the day of hospitalization was significantly higher for patients who received medications contraindicated for PACD than for those who did not receive them (p = 0.010).<h4>Conclusions</h4>About 20% of patients with PACD received medications potentially contraindicated for PACD, such as anticholinergics. Attention should be paid to patients prescribed multiple drugs for adverse events, such as increase in intraocular pressure.

DOI： 10.1186/s40780-021-00196-w

PubMed

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.urolonc.2020.09.013

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

<h4>Purpose</h4>Switch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases.<h4>Methods</h4>The medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing MRONJ in the ZA-to-denosumab group. Secondary endpoints were probability of MRONJ and the relationship between risk factors and the time to the development of MRONJ.<h4>Results</h4>Among the 795 patients included in this study, 65 (8.2%) developed MRONJ. The incidence of MRONJ was significantly higher in the ZA-to-denosumab group than in the ZA group [7/43 (16.3%) vs. 19/350 (5.4%), p = 0.007]. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment [hazard ratio (HR), 2.41; 95% confidence interval (CI), 1.37-4.39; p = 0.002], ZA-to-denosumab treatment (HR, 4.36; 95% CI, 1.63-10.54, p = 0.005), tooth extraction after starting ZA or denosumab (HR, 4.86; 95% CI, 2.75-8.36; p < 0.001), and concomitant use of antiangiogenic agents (HR, 1.78; 95% CI, 1.06-2.96; p = 0.030) were significant risk factors for MRONJ.<h4>Conclusion</h4>Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.

DOI： 10.1007/s00280-021-04262-w

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

WHAT IS KNOWN AND OBJECTIVE: The distribution of tacrolimus (TAC), an immunosuppressant used during cord blood transplantation (CBT)-one of the haematopoietic stem cell transplantations, to red blood cell (RBC) is approximately 90% in whole blood. In CBT patients, the total RBC count shows dramatic fluctuation due to conditioning before transplantation, including anticancer agents and total body irradiation, as well as RBC transfusions during the treatment period. Therefore, the amount of TAC in whole blood may show wide variation. However, therapeutic drug monitoring (TDM) of TAC has been performed based on the whole blood concentration. In this study, to contribute to TDM of TAC in CBT, we performed the population pharmacokinetic (PPK) analysis of TAC in 56 CBT patients and investigated the factors that affected the concentration of TAC, focusing the variation of RBC count. METHOD: A one-compartment model was applied to the observed whole blood TAC concentrations, and a PPK analysis was conducted with a non-linear mixed effect model. RESULTS AND DISCUSSION: Our final PPK model indicated good robustness and accuracy. In addition, haemoglobin (Hb) level was an influential covariate on Vd, which was expressed as Vd(L) = 91.4 × (Hb/8.2)(-1.07) . WHAT IS NEW AND CONCLUSION: In this study, our results showed the necessity for the Hb level monitoring during TDM of TAC in CBT patients and provided useful information for improving TDM strategy of TAC.

DOI： 10.1111/jcpt.13279

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. METHODS: The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. RESULTS: Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). CONCLUSION: The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

DOI： 10.1007/s00520-021-06018-x

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Drug-induced gastrointestinal obstruction (DIGO) and gastrointestinal perforation (DIGP) may be the result of gastrointestinal hypomotility and severe constipation, which may lead to potentially fatal complications of bowel ischemia, sepsis and perforation. We evaluated the onset profile of DIGs (DIGO and DIGP) associated with prescription drugs by analyzing data in the Japanese Adverse Drug Event Report (JADER) database. We selected 161 DIG-related drugs and categorized them into 19 classes based on the Anatomical Therapeutic Chemical (ATC) Classification System. Finally, we focused on 58 drugs and conducted subsequent analyses for the time-to-onset and outcomes. We extracted 79 preferred terms (PTs) with the strings "ileus," "stenosis," "obstruction," "obstructive," "impaction," "perforation," "perforated," "hypomotility," and "intussusception" from the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) of SMQ20000104: gastrointestinal perforation, ulcer, hemorrhage, obstruction non-specific findings/procedures; SMQ20000105: gastrointestinal obstruction; and SMQ20000107: gastrointestinal perforation. Among the 667, 729 reports in the JADER database submitted between April 2004 and November 2020, we identified 11,351 occurrences of DIGs. The reporting odds ratios (RORs) (95% confidence interval) of "barium sulfate containing X-ray media," "drugs for treatment of hyperkalemia and hyperphosphatemia," and "oral bowel cleanser" were 142.0 (127.1-158.6), 25.8 (23.1-28.8), and 29.7 (24.8-35.6), respectively. The median number of days (interquartile range) until the onset of an adverse event caused by each drug category was as follows: barium sulfate containing X-ray contrast media [2.0 (1.0-3.0)], diazepines, oxazepines, thiazepines, and oxepines [8.0 (8.0-18.5)], drugs for treatment of hyperkalemia and hyperphosphatemia [29.0 (8.0-55.0)], non-selective monoamine reuptake inhibitors [19.0 (7.0-47.5)], and oral bowel cleanser [0.0 (0.0-0.0)]. Depending on the drug, the time to onset of side effects ranged from days to several months. Our results highlighted the need to perform detailed monitoring of each drug for possible association with DIGs, which might otherwise have fatal consequences.

DOI： 10.3389/fphar.2021.692292

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

WHAT IS KNOWN AND OBJECTIVE: Immune checkpoint inhibitors can cause immune-related adverse events (irAEs). Improved monitoring systems for irAEs, which include laboratory tests by a qualified multidisciplinary team, might prevent patients from irAE-associated events. Kobe City Medical Center General Hospital developed protocol-based pharmacist-facilitated laboratory tests named protocol-based pharmacotherapy management (PBPM) to aid the administration of immunotherapy to patients with lung cancer. The protocol defines the laboratory test items and times at which they should be performed. It requires pharmacists to check laboratory orders initiated by physicians and enter additional test items if the orders are incomplete. We evaluated the efficacy of PBPM in irAE monitoring and compared it with those of conventional care systems. METHODS: From January 2016 to March 2018, 114 patients with lung cancer received immunotherapy, which was managed by conventional care (conventional group). From April to September 2018, 62 patients were managed by PBPM (PBPM group), among those 28 patients were transited from conventional group to PBPM group. Data on whether the laboratory tests were conducted or omitted were collected retrospectively for the conventional group and prospectively for the PBPM group. RESULTS: Within the conventional group, 4604 (87.6%) out of the 5253 laboratory test items were ordered by physicians. Of the remaining 649 test items, 224 (4.3%) items were added by physicians based on recommendations by pharmacists. However, of the 1581 (86.6%, from among 1826) test items that were previously ordered by physicians, only 231 (12.7%) test items were added by pharmacists. The execution rate was found to be significantly higher in the PBPM group (99.2% vs 91.9%, P < .001). WHAT IS NEW AND CONCLUSION: PBPM-based pharmacist-facilitated laboratory monitoring systems provided higher executing rate of laboratory order to monitor irAEs during immunotherapy.

DOI： 10.1111/jcpt.13207

PubMed

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jcpt.13207

Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media {SA}  

<jats:p><jats:bold>Background:</jats:bold> Pirfenidone is an anti-fibrotic agent used to treat patients with idiopathic pulmonary fibrosis (IPF). Managing adverse drug events and ensuring compliance with pirfenidone treatment for a prolonged period are important to reduce the rate of disease progression. To maximize the benefits of pirfenidone treatment, we established and evaluated an ambulatory care pharmacy practice, a model of pharmacist–physician collaborative management, for patients receiving pirfenidone.</jats:p><jats:p><jats:bold>Methods:</jats:bold> We conducted a retrospective chart review of 76 consecutive patients treated with pirfenidone in the Kobe City Medical Center General Hospital, Japan, between January 2012 and January 2019. The first group (61 patients) received pirfenidone treatment as conventional management, whereas the second group (15 patients) started pirfenidone based on collaborative pharmacist–physician management. The drug discontinuation rate and time to drug discontinuation were compared between the groups. To analyze factors associated with pirfenidone discontinuation, we used a multivariate Cox regression analysis to evaluate the baseline characteristics of patients, including those receiving the collaborative management. Clinical outcomes were compared using a propensity score matched analysis.</jats:p><jats:p><jats:bold>Results:</jats:bold> In the collaborative management group, pharmacists made 56 suggestions, including suggestions for supportive care (51 suggestions), to the physicians. Among these suggestions, 52 were accepted by the physicians. The discontinuation rates at 3 [6.7% (1/15) vs. 26.2% (16/61)] and 6 [9.1% (1/11) vs. 36.1% (22/61)] months were lower in the collaborative management group than in the conventional management group. Multivariate analysis revealed that collaborative management [hazard ratio (HR) 0.34, 95% CI 0.08–0.96, <jats:italic>p</jats:italic> = 0.041] and predicted baseline forced vital capacity &amp;lt;60% (HR 2.13, 95% CI 1.17–3.85, <jats:italic>p</jats:italic> = 0.015) were significantly associated with pirfenidone discontinuation. The time to drug discontinuation was also significantly longer in the collaborative management group than in the conventional management group (<jats:italic>p</jats:italic> = 0.034, log-rank test). Propensity score matched analysis confirmed a significant correlation between collaborative management and drug discontinuation time (HR 0.20, 95% CI 0.03–0.84, <jats:italic>p</jats:italic> = 0.027).</jats:p><jats:p><jats:bold>Conclusions:</jats:bold> We established an ambulatory care pharmacy practice for out-patients with IPF receiving pirfenidone. The results suggest that collaborative management may help prevent pirfenidone discontinuation compared with conventional management.</jats:p>

DOI： 10.3389/fphar.2020.529654

Language：English   Publishing type：Research paper (scientific journal)  

Objectives: Reye’s syndrome is a rare and potentially fatal illness that is defined as
encephalopathy accompanied by liver failure. The aim of this study was to
assess Reye’s syndrome profiles by analyzing data from the spontaneous
reporting system database. Methods: We analyzed reports of Reye’s syndrome using the US Food and Drug
Administration Adverse Event Reporting System and the Japanese Adverse Drug
Event Report databases. The reporting odds ratio and proportional reporting
rate were used to detect the pharmacovigilance signal. Results: The US Food and Drug Administration Adverse Event Reporting System contains
12,201,620 reports from January 2004 to June 2020, of which 186 are on
Reye’s syndrome. The Japanese Adverse Drug Event Report contains 646,779
reports from April 2004 to September 2020, of which 30 are on Reye’s
syndrome. In the US Food and Drug Administration Adverse Event Reporting
System database, the reporting odds ratios (95% confidence interval, number
of cases) of aspirin, diclofenac, ibuprofen, acetaminophen, and valproate
sodium were 404.6 (302.6–541.0, n = 80), 15.1 (6.7–34.1, n = 6), 26.2
(16.1–42.6, n = 18), 10.7 (5.5–20.9, n = 9), and 47.1 (26.2–84.6, n = 12),
respectively. In the Japanese Adverse Drug Event Report database, the
reporting odds ratios (95% confidence interval, number of cases) of aspirin,
diclofenac, ibuprofen, loxoprofen, acetaminophen, and valproate sodium were
14.1 (5.4–36.8, n = 5), 51.7 (22.2–120.5, n = 7), 135.0 (40.8–446.2, n = 3),
17.6 (6.7–46.0, n = 5), 24.0 (9.2–62.6, n = 5), and 13.8 (3.3–57.9, n = 2),
respectively. The reported number of female patients aged 30–39 years was
the highest in the Japanese Adverse Drug Event Report. Conclusion: Although the frequency of the occurrence of Reye’s syndrome is low, the
possible risk of the disease occurring in adult females should be
considered.

DOI： 10.1177/2050312120974176

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

DOI： 10.1248/bpb.b20-00428

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/cts.12827

PubMed

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cts.12827

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE:The aim of our study was to characterize the clinical features of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database. METHODS:The irAEs were defined using the preferred terms of the Medical Dictionary for Regulatory Activities. irAEs were categorized as follows: adrenal insufficiency, colitis, eye diseases, hematological disorder, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia gravis, myocarditis, nephritis/renal dysfunction, pneumonitis, rash, and type 1 diabetes mellitus. We used several indices such as reporting odds ratio (ROR) to assess disproportionality in pharmacovigilance data, time-to-onset analysis using Weibull shape parameters, and the association rule mining technique to evaluate possible risk factors between variables in the spontaneous reporting system database. RESULTS:The JADER database contained 534 688 reports from April 2004 to June 2018. The RORs of pneumonitis including interstitial lung disease for nivolumab, pembrolizumab, and ipilimumab were 7.02 (95% confidence interval: 6.55-7.52), 9.08 (8.28-9.97), and 1.74 (1.27-2.38), respectively. The median onsets (quartiles, 25-75%) of myocarditis caused by nivolumab and pembrolizumab were 28.0 (15.5-60.5) and 18.0 (13.0-44.5) days, respectively. Co-therapy with nivolumab and ipilimumab may be associated with irAEs in several categories as per the association rule mining analysis. CONCLUSION:Our results demonstrated a potential risk of irAEs associated with ICIs, based on RORs and time-to-onset analysis. Furthermore, our findings indicated that patients receiving nivolumab and ipilimumab as co-therapy should be carefully monitored.

DOI： 10.1002/pds.5108

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We retrospectively obtained data of patient background and pretreatment characteristics from medical records and identified the predictive factors of febrile neutropenia (FN) in patients with non-small cell lung cancer (NSCLC) treated with docetaxel alone or in combination with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab.Patients were eligible for inclusion in the study if they were 20 years or older, diagnosed with NSCLC, and received docetaxel monotherapy alone or in combination with bevacizumab at the Department of Respiratory Medicine, Kobe City Medical Center General Hospital, between July 1, 2011, and March 31, 2018.Eighty-one patients with recurrent or advanced NSCLC were included. Multivariate stepwise logistic regression analysis with backward selection revealed that lower baseline Eastern Cooperative Oncology Group performance status (ECOG-PS) scores of 1 and 2 (odds ratio [OR], 5.098; 95% confidence interval [CI], 1.045-24.879, p=0.021) and baseline platelet count below 18.8 x 104/µL (OR, 3.861; 95% CI, 1.211-12.311, p=0.022) were significant factors influencing the FN occurrence rate.Our results demonstrated that ECOG-PS 1-2 and lower baseline platelet count were significant risk factors of FN in patients with NSCLC receiving docetaxel-based chemotherapy. Moreover, the combination of anti-VEGF antibodies and docetaxel might be associated with increased FN frequency. Despite the limitations of this study including its retrospective design, single-center site, and small sample size, baseline ECOG-PS score and platelet count may be regarded as important indices to identify patients for prophylactic granulocyte-colony stimulating factor (G-CSF) treatment before docetaxel-based chemotherapy.

DOI： 10.1248/bpb.b20-00266

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

WHAT IS KNOWN AND OBJECTIVE:Edoxaban has three dose adjustment factors (creatinine clearance, 15-50 mL/min; body weight, 60 kg or less; and concomitant medication with potent P-glycoprotein inhibitors) to prevent bleeding that results from elevated blood concentrations of the drug. A dose reduction (from 60 to 30 mg/day of edoxaban) is recommended for patients with even one of those. However, it is not clear whether 30 mg/day of edoxaban is adequate for patients with multiple dose adjustment factors. We thus investigated the association between the number of the dose adjustment factors and bleeding risk in patients receiving edoxaban. METHODS:We retrospectively analysed 198 patients who received 30 mg/day of edoxaban between April 2015 and March 2017 with follow-up for 1 year. RESULTS:The incidences of major bleeding were 1.4%, 7.3% and 20.0% in patients with 0-1, 2 and 3 dose adjustment factors, respectively. The Cox proportional hazards regression model revealed that the risk of major bleeding was higher in patients with 2 (hazard ratio [HR]: 5.80, 95% confidence interval [CI]: 0.96-44.05, P = .055) or 3 (HR: 17.70, 95% CI: 2.12-147.70, P = .012) dose adjustment factors than in those with 0-1 dose adjustment factor. WHAT IS NEW AND CONCLUSION:This is the first study to evaluate the risk of bleeding in patients administered 30 mg/day of edoxaban based on the number of dose adjustment factors in clinical practice. For patients receiving edoxaban, as the number of the dose adjustment factors increases, the risk of major bleeding is elevated. In patients with multiple dose adjustment factors, not only one level of dose reduction, but further dose reductions may be considered. Further studies with a larger sample size are needed to confirm these findings.

DOI： 10.1111/jcpt.13065

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Clostridium difficile-associated colitis (CDAC) may cause gastrointestinal illness, ranging in severity from mild diarrhea to fulminant colitis and even mortality. The purpose of this study was to evaluate anti-infective-related CDAC profiles using the Japanese Adverse Drug Event Report (JADER) database. Methods: We selected case reports of adverse events of CDAC as specified in the Medical Dictionary for Regulatory Activities. The association between the number of administered anti-infectives and aging was evaluated using reporting odds ratio (ROR) and adjusted for covariates using multiple-logistic regression. We also evaluated anti-infective-related CDAC-onset profiles using Weibull shape parameter. Results: The JADER database contained 534 688 reports from April 2004 to June 2018. There were 1222 anti-infective related CDAC events. The top five anti-infectives were as follows: third-generation cephalosporins (Anatomical Therapeutic Chemical (ATC) code: J01DD, 313 cases), fluoroquinolones (ATC code: J01MA, 201 cases), macrolides (ATC code: J01FA, 146 cases), carbapenems (ATC code: J01DH, 143 cases), and penicillins with extended spectrum (ATC code: J01CA, 103 cases). The adjusted RORs (95% confidence interval) in individuals using 1, 2, and ≥ 3 anti-infectives were 8.88 (7.05-11.18), 9.77 (6.89-13.86), and 18.39 (11.85-28.54), respectively. Moreover, 47.2% of CDACs occurred within 7 days of anti-infective therapy initiation. The adjusted ROR of interaction terms of ≥ 70 years × 1 drug was 21.81 (14.56-32.68). Conclusion: Our results suggest that the number of administered anti-infectives and patient age are associated with CDAC. These data may be particularly beneficial to prescribers and would contribute to improving the management of CDAC.

DOI： 10.7150/ijms.43789

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We investigated whether use of hypnotic drugs, including benzodiazepine receptor agonists, as well as ramelteon and suvorexant are associated with fall incidents in elderly inpatients aged no less than 75 years, who were hospitalized at an acute care general hospital in Japan, between November 1st, 2016 and October 31st, 2017. Multivariate analysis results were reported as odds ratio (OR) with 95% confidence interval (CI). Following to a case-crossover study protocol, the time windows of the case and the control days were assigned to the day or the days, which are one day or 2-8 d before the fall incidents, respectively. In the enrolled 111 patients, the accumulated total available numbers of the cases and the control days were 111 and 554 patient days, respectively. Hypnotic drug use was significantly associated with fall incidents (OR: 2.85, 95% CI: 1.03-7.90, p = 0.04). Especially benzodiazepine receptor agonists (OR: 5.79, 95% CI: 1.52-22.1, p = 0.01) showed statistically significant association with fall incidents. In contrast, neither ramelteon (OR: 7.95, 95% CI: 0.72-87.9, p = 0.09) nor suvorexant (OR: 0.25, 95% CI: 0.06-1.06, p = 0.06) were significantly associated with fall incidents. Thus, benzodiazepine receptor agonists, but not ramelteon or suvorexant, showed significant association with fall incidents. Therefore, special care should be taken especially when benzodiazepine receptor agonists are administrated to elderly subjects. In contrast, fall risk may be much less in patients treated with ramelteon or suvorexant. These results could help us to conduct safer drug treatment for insomnia patients aged no less than 75 years.

DOI： 10.1248/bpb.b19-00684

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Edoxaban is used to prevent and treat stroke or systemic embolism such as venous thromboembolism. Although bleeding is the most common complication of anticoagulants, only a few studies have addressed the safety of direct oral anticoagulants in East Asian patients. In this study, we investigated the risk factors for bleeding in Japanese patients receiving edoxaban. A retrospective review of the records of 198 patients who received 30 mg/day edoxaban in our hospital between April 2015 and March 2017 was performed. Subsequently, these patients were followed up to 1 year. Seven (3.5%) and 22 (11.1%) patients developed major bleeding and clinically relevant bleeding, respectively. In the univariate Cox regression analyses, low baseline hemoglobin levels (p = 0.002) and low baseline creatinine clearance (p = 0.020) were significantly associated with major bleeding. Multivariate Cox regression analysis revealed that a low baseline hemoglobin level was a significant risk factor for major bleeding and clinically relevant bleeding [hazard ratio 1.67 per 1 g/dL decrease (95% confidence interval 1.14-2.56, p = 0.008) and hazard ratio 1.31 per 1 g/dL decrease (95% confidence interval 1.06-1.62, p = 0.013), respectively]. Baseline hemoglobin level in quartiles also showed a quartile-dependent decrease in major bleeding and clinically relevant bleeding event. These results suggest that low baseline hemoglobin level is a significant risk factor for both major bleeding and clinically relevant bleeding in Japanese patients receiving edoxaban. Thus, these patients should be carefully monitored.

DOI： 10.1248/bpb.b19-00799

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s40780-018-0113-3

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this retrospective study was to identify variable factors affecting tacrolimus blood concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n = 73). The blood concentration/dose ratio of tacrolimus immediately before the change from continuous infusion (C/Div) was compared with that between 3 and 5 days after the change to oral administration (C/Dpo). Median (C/Dpo)/(C/Div) was 0.21 (range 0.04-0.58). Multiple regression analysis showed that concomitant use of oral itraconazole or voriconazole significantly increased the (C/Dpo)/(C/Div) of tacrolimus (p = 0.002), probably owing to the inhibition of enterohepatic cytochrome P450 3A4. In addition, 5 of 18 (28%) patients who had the lowest quartile (C/Dpo)/(C/Div) values developed acute graft-versus-host-disease (GVHD), which was significantly higher than in others [5 of 55 (9%) patients, p = 0.045]. Although the switch from intravenous to oral administration at a ratio of 1:5 appeared to be appropriate, a lower conversion ratio was suitable in patients taking oral itraconazole or voriconazole. In patients whose blood concentration decreases after the switch, the development of GVHD should be monitored and tacrolimus dosage should be readjusted to maintain an appropriate blood concentration.

DOI： 10.1007/s12185-016-2135-7

PubMed

Language：Japanese   Publisher：(一社)日本医療薬学会  

集中治療室における注射剤配合変化早見表の作成と有用性について検討した。ICUにおける6ヵ月間の注射剤使用実績を基に、主に持続静注され、薬剤師が特に日常診療で使用頻度が高いと判断した注射剤35品目を対象とした。作成した配合変化早見表において、薬剤名(商品名)は薬効別に表記することで、日常診療で実際に配合されやすい薬剤同士が近傍に配置されるよう工夫した。規格pHならびに製剤学的特徴については、十分な根拠資料がない場合において配合可否の推測に有用であるため、それぞれ薬剤名の右列に掲載した。製剤学的特徴の右列には薬剤毎にアルファベットを付し、行列のアルファベットを交差させることで配合可否の記号を確認できる形式とした。配合変化早見表の有用性は、「とても有用」または「やや有用」と評価した対象者の割合は、看護師では合計86.9%、医師では合計100%であった。配合変化早見表の運用により、調査時間は運用前と比較し運用後で有意に短縮した。相談に対する調査時間も配合変化早見表の運用前と比較し運用後で有意に短縮した。

DOI： 10.5649/jjphcs.42.286

Language：Japanese   Publisher：(一社)日本医療薬学会  

実施している患者教育の有用性について、エルロチニブおよびゲフィチニブ導入初期および退院時における患者理解度を比較評価した。解析対象は39名(男性20名、女性19名、年齢中央値67歳)で、服薬歴はエルロチニブ1名、ゲフィチニブ7名であった。正答率は65歳以上で導入時76.2、退院時95.2、65歳未満で導入時71.4、退院時95.2とそれぞれ有意に改善した。服薬歴の有無によるエルロチニブ、ゲフィチニブ導入時、退院時の理解度に差は認めなかった。

Language：English   Publishing type：Research paper (scientific journal)  

Pemetrexed plus carboplatin therapy is widely administered to patients with non-squamous non-small cell lung cancer. Although severe neutropenia is often observed during this combination therapy, its predictive factors are unknown. Therefore, we investigated the predictive factors for severe neutropenia in 77 patients treated with this combination therapy at the Department of Respiratory Medicine, Kyushu University Hospital, between September 2009 and September 2013. All data were retrospectively collected from the electronic medical record system, and univariate and multivariate logistic regression analyses were performed to identify risk factors for grade 3 or 4 neutropenia. Among the 77 patients, 34 (44%) developed grade 3 or 4 neutropenia. Multivariate analysis revealed that lower baseline hemoglobin values (odds ratio [OR], 1.97 per 1 g/dL decrease; 95% confidence interval [CI], 1.39-2.99, p<0.01) and lower baseline neutrophil counts (OR, 1.71 per 1000/mm(3) decrease; 95% CI, 1.14-2.71, p=0.01) were significantly associated with grade 3 or 4 neutropenia. During 4 courses of pemetrexed plus carboplatin therapy, the incidence of grade 3 or 4 neutropenia in patients with baseline hemoglobin values of <11.6 g/dL was significantly higher than that in patients with values of ≥11.6 g/dL [84% (16/19) vs. 31% (18/58), p<0.001]. In conclusion, patients with lower baseline neutrophil counts or lower baseline hemoglobin values, especially those with baseline hemoglobin values of <11.6 g/dL, should be monitored more carefully during pemetrexed plus carboplatin therapy.

DOI： 10.1248/bpb.b15-00162

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Differences in error rates between pharmacists and nurses in terms of drug confirmation have not been studied. The purpose of this study was to analyze differences in error rates between pharmacists and nurses from the viewpoint of error categories, and to clarify differences in recognition regarding drug name similarity. METHODS: In this study, preparation errors and incidents were classified into three categories (drug strength errors, drug name errors, and drug count errors) to investigate the influence of error categories on pharmacists and nurses. In addition, errors in two categories (drug strength errors and drug name errors) were reclassified into another two error groups, to investigate the influence of drug name similarity on pharmacists and nurses: a "drug name similarity (-) group" and a "drug name similarity (+) group". Then, differences in error rates of pharmacists and those of nurses were analyzed respectively within three categories and two groups. Furthermore, differences in error rates between pharmacists and nurses were analyzed in each of the three categories and two groups. RESULTS: Error rates of pharmacists for both drug strength errors and drug name errors were significantly higher than that for drug count errors, and similar results were obtained for nurses (P < 0.05). However, there were no significant differences in error rates between pharmacists and nurses in each of the three categories. Furthermore, error rate of nurses was significantly higher than that of pharmacists in the drug name similarity (+) group (P < 0.05), while there was no significant difference in error rates between pharmacists and nurses in the drug name similarity (-) group. CONCLUSIONS: These results suggest that in contrast to pharmacists, nurses are easily affected by similarities in drug names. Therefore, pharmacists should offer information on medications having plural strengths or similar names to nurses, in order to minimize damage to patients resulting from errors.

DOI： 10.1186/s40780-015-0017-4

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Severe hypocalcemia sometimes develops during denosumab treatment for bone metastases from cancer and is, therefore, an important issue. However, limited information is available on the risk factors for hypocalcemia and the appropriate interval for monitoring serum calcium concentration. OBJECTIVE: The present study aimed to identify the risk factors for grade ≥2 hypocalcemia and to investigate the time course of serum calcium concentrations in patients receiving denosumab for bone metastases from cancer. METHOD: The medical records of 66 cancer patients treated with denosumab between April 2012 and August 2013 were retrospectively reviewed. RESULT: Of the 66 enrolled patients, 11, 5, and 1 developed grade 1, 2, and 3 hypocalcemia, respectively. All 4 patients with a baseline estimated glomerular filtration rate (eGFR) of <30 mL/min developed hypocalcemia. Hypocalcemia occurred in only 20%, 24%, and 15% of patients with an eGFR of 30 to 59, 60 to 89, and ≥90 mL/min, respectively. Multivariate logistic regression analysis revealed that lower eGFR values (odds ratio, 1.72 per 10 mL/min decrease, P = 0.02) were significantly associated with grade ≥2 hypocalcemia. In 11 patients who developed hypocalcemia during the first treatment course, the mean calcium concentrations decreased from 9.8 mg/dL at baseline to 8.4 mg/dL during the first week and reached a nadir of 8.1 mg/dL during the second week. CONCLUSION: Our results support more frequent monitoring of serum calcium concentrations at baseline and during the first 2 weeks of treatment in patients receiving denosumab, especially those with an eGFR <30 mL/min.

PubMed

Language：Japanese   Publisher：(一社)日本病院薬剤師会  

精神科チーム医療では、薬剤師が薬物療法に関する情報を収集・管理し、処方の妥当性を評価することによって、医師の処方設計を支援することが求められる。しかしながら実臨床では、マンパワーの不足により十分な薬学的関与を行うことが困難な状況である。そこで我々は、情報管理と処方評価の効率化および標準化を目的として、精神科薬物療法のモニタリングに有用なシステムを構築した。市販のデータベースソフトを用いて、向精神薬140品目の薬剤情報を登録し、患者情報および処方情報を入力した。本システムの導入により、患者情報および処方情報の管理に要する時間が有意に短縮した。さらに、本システムを活用し、薬物療法モニタリングシートおよび薬歴情報シートを作成することによって、処方提案を円滑に行うことが可能となった。以上のことから、本システムは、精神科病棟薬剤師業務の効率化および標準化に有用と考えられた。(著者抄録)

Language：Japanese   Publisher：(公社)日本薬学会  

Language：English   Publishing type：Research paper (scientific journal)  

STUDY OBJECTIVE: To evaluate the efficacy and safety of aprepitant added to standard antiemetic regimens used in high-dose chemotherapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT). DESIGN: Retrospective medical record review. SETTING: Hematology ward of a university hospital in Japan. PATIENTS: Of 88 patients treated with high-dose chemotherapy followed by allo-HSCT, 46 received aprepitant and granisetron as antiemetic therapy (between April 1, 2010, and December 31, 2011), and 42 received granisetron alone (between April 1, 2008, and March 31, 2010). INTERVENTIONS: Patients in both groups received 3 mg of granisetron intravenously 30 minutes before the administration of anticancer drugs. In the aprepitant group, 125 mg of aprepitant was administered orally 60-90 minutes before the administration of the first moderately to highly emetogenic anticancer drug. On the following days, 80 mg of aprepitant was administered orally every morning. The mean administration duration of aprepitant was 3.3 days (range 3-6 days). MEASUREMENTS AND MAIN RESULTS: The primary objective was to evaluate the percentage of patients who achieved complete response (CR; no vomiting and none to mild nausea). The CR rate in the aprepitant group was significantly higher than that in the control group (48% vs 24%, p=0.02). Multivariate analysis showed that nonprophylactic use of aprepitant was associated with failure to achieve CR (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.13-7.99, p=0.03). The frequency of abdominal pain was lower in the aprepitant group (9% vs 25%, p=0.03). Rates of other frequently observed adverse drug events were similar between groups. There was no significant difference in neutrophil engraftment (median 18 vs 17 days), platelet engraftment (median 32 vs 32 days), the incidence of acute graft-versus-host-disease (63% vs 55%, p=0.52), viral infection (74% vs 67%, p=0.49), or 1-year overall survival (63% vs 62%, p=0.90) between the two groups. CONCLUSIONS: The addition of aprepitant to granisetron increases the antiemetic effect without influencing transplantation-related toxicities in allo-HSCT.

DOI： 10.1002/phar.1294

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Antiemetic effectiveness and safety of aprepitant in patients with hematologic malignancy receiving multiday chemotherapy were evaluated. METHODS: All data were retrospectively collected from the Kyushu University Hospital's electronic medical record system. Patients age 20 years or older with hematologic malignancies who received multiday chemotherapy were included in the study. All patients received 3 mg of granisetron i.v. 30 minutes before chemotherapy administration. Patients in the aprepitant group received 125 mg of aprepitant orally 60-90 minutes before administration of the first moderately to highly emetogenic chemotherapy (day 1). On day 2 or thereafter, an 80-mg oral dose of aprepitant was administered in the morning for up to five days. The primary endpoint was the percentage of patients who achieved complete response (CR). RESULTS: A total of 42 patients were treated with aprepitant and granisetron as antiemetic prophylaxis between April and December 2010 (aprepitant group), and 40 patients were treated with only granisetron between March 1, 2009, and March 31, 2010, before the introduction of aprepitant. The percentage of patients who achieved CR in the aprepitant group was significantly higher than that in the control group (p = 0.01). Factors that were significantly associated with non-CR included the prophylactic use of aprepitant and chemotherapies containing ≥4 g/m(2)/day of cytarabine. The rates of adverse drug events (ADEs) did not significantly differ between groups. CONCLUSION: The addition of aprepitant to granisetron increased the antiemetic effect without influencing ADEs in patients treated with moderately to highly emetogenic multiday chemotherapy for hematologic malignancies.

DOI： 10.2146/ajhp120363

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Intravenous injection of bendamustine often causes venous irritation and also deteriorates the patient's quality of life. Thus, we evaluated the risk factors associated with venous irritation induced by bendamustine in patients with follicular lymphoma or mantle cell lymphoma. We also evaluated the effectiveness of intervention of changing the preparation procedure for bendamustine. All data were retrospectively collected from the electronic medical record system. In the initial analysis of the total 43 courses of bendamustine therapy, most patients (88%) were administered bendamustine with 250 mL of diluent according to the bendamustine package insert in Japan. The median concentration of bendamustine solution (0.56 mg/mL vs. 0.24 mg/mL) and the incidences of venous irritation (66% vs. 0%, p=0.01) were significantly different between the patients receiving bendamustine at 250 mL and 500 mL of diluent. Based on this result, we proposed changing the final volume of bendamustine dissolution from 250 to 500 mL, which is recommended in other countries. After this intervention, the incidence of venous irritation was significantly reduced from 58 to 20% (p=0.02). The incidence of venous irritation increased in a concentration-dependent manner (≤0.40 mg/mL: 6%; 0.41-0.60 mg/mL: 62%, p<0.001; >0.60 mg/mL: 75%, p<0.001). We conclude that a high concentration bendamustine solution is a risk factor for venous irritation and that 500 mL of diluent is ideal. To further reduce the incidence of venous irritation, the concentration of bendamustine solution is recommended to be 0.40 mg/mL or less.

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

For patients receiving high-dose chemotherapy, a 5-hydroxytryptamine 3 receptor antagonist combined with dexamethasone is a standard antiemetic therapy. Despite this prophylactic anti-emetic treatment, many patients still suffer from uncontrollable emesis. In this study, we retrospectively evaluated the antiemetic effectiveness and safety of aprepitant (a neurokinin-1 receptor antagonist) in addition to 5-HT3 antagonist in Japanese patients with hematologic malignancy receiving high-dose chemotherapy prior to autologous peripheral blood stem cell transplantation (auto-PBSCT). Twenty-six patients received aprepitant and granisetron (the aprepitant group), whereas, 22 patients received granisetron alone (the control group). All patients received 3 mg of granisetron intravenously 30 min before chemotherapy administration. Patients in the aprepitant group additionally received 125 mg of aprepitant 60-90 min before administration of the first moderately to highly emetogenic chemotherapy. On the next day or thereafter, 80 mg of aprepitant was administered in the morning until the last administration of moderately to highly emetogenic anticancer drugs. The percentage of patients who achieved complete response (CR), defined as no emesis with only grade 1-2 nausea, in the aprepitant group was significantly higher than that in the control group (42% vs. 5%, p=0.003). Logistic regression analysis showed that non-prophylactic use of aprepitant was significantly associated with non-CR. The frequencies of adverse drug events (ADEs) were not significantly different between two groups. In conclusion, the results of this study suggest that the addition of aprepitant to granisetron can improve the antiemetic effect without increasing ADEs in patients receiving high-dose chemotherapy prior to auto-PBSCT.

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Neutropenia is one of the most frequent and dose-limiting toxicities in amrubicin (AMR) therapy. However, the predictive factors for the development of severe neutropenia in AMR therapy remain unknown. METHODS: The subjects were 61 advanced lung cancer patients treated with AMR monotherapy. All data were retrospectively collected from the electronic medical record system. A stepwise logistic regression analysis was performed to identify risk factors for grade 3-4 neutropenia. RESULTS: Of a total 61 patients, 50 were male and 11 were female. The median dose of AMR was 35.0 mg/m(2). The incidence of grade 3-4 neutropenia during the first course was 62%. In multivariate analysis, female gender (OR = 6.68; 95% CI 1.01-134.15; p = 0.049), higher AMR doses (40 mg/m(2) or more) (OR = 5.98; 95% CI 1.77-23.74; p = 0.003), and lower hematocrit values (OR = 2.04 per 5% decrease; 95% CI 1.04-4.38; p = 0.036) were significantly associated with severe neutropenia induced by AMR. CONCLUSION: The present results suggest that female gender, higher doses of AMR, and lower baseline hematocrit values are predictive factors associated with severe neutropenia induced by AMR in patients with advanced lung cancer. Patients who have these predictive factors should be monitored carefully and considered for early granulocyte colony-stimulating factor support.

DOI： 10.1159/000345617

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The aim of this study was to evaluate the effectiveness of prophylactic treatment with laxatives and antiemetics on the incidence of gastrointestinal adverse reactions such as constipation, nausea and vomiting in cancer patients who received oral opioid analgesics for the first time. METHODS: A multi-institutional retrospective study was carried out, in which 619 eligible hospitalized patients receiving oral opioid analgesics for cancer pain were enrolled from 35 medical institutions. The primary endpoint was the incidence of opioid-induced side effects in patients receiving prophylactic medication. Odds ratios of the incidence of adverse reactions in the absence or presence of premedication obtained from several institutions were subjected to a meta-analysis. RESULTS: Among 619 patients, the incidence of constipation was significantly lower in patients receiving laxatives, including magnesium oxide, as premedication than in those without them (34% vs. 55%, odds ratio=0.432, 95% confidence interval=0.300-0.622, P<0.001). However, the incidence of nausea or vomiting was similar regardless of prophylactic medication with dopamine D2 blockers. The results of the meta-analysis revealed that prophylactic laxatives significantly reduced the incidence of constipation (overall odds ratio=0.469, 95% confidence interval=0.231-0.955, P=0.037), whereas dopamine D2 blockers were not effective in preventing opioid-induced nausea or vomiting. DISCUSSION: We showed evidence for the effectiveness of premedication with laxatives for prevention of opioid-induced constipation. However, premedication with dopamine D2 blockers was not sufficient to prevent nausea or vomiting.

DOI： 10.1097/AJP.0b013e318237d626

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Oxaliplatin is a key drug for colorectal cancer, but it causes acute peripheral neuropathy (triggered by cold) and chronic neuropathy (sensory and motor neuropathy) in patients. Neurotropin, a non-protein extract from the inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic pains. In the present study, we investigated the effect of neurotropin on the oxaliplatin-induced neuropathy in rats. Repeated administration of oxaliplatin caused cold hyperalgesia from Day 5 to Day 29 and mechanical allodynia from Day 15 to Day 47. Repeated administration of neurotropin relieved the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia, and inhibited the oxaliplatin-induced axonal degeneration in rat sciatic nerve. Neurotropin also inhibited the oxaliplatin-induced neurite degeneration in cultured pheochromocytoma 12 (PC12) and rat dorsal root ganglion (DRG) cells. On the other hand, neurotropin did not affect the oxaliplatin-induced cell injury in rat DRG cells. These results suggest that repeated administration of neurotropin relieves the oxaliplatin-induced mechanical allodynia by inhibiting the axonal degeneration and it is useful for the treatment of oxaliplatin-induced neuropathy clinically.

DOI： 10.1016/j.ejpain.2010.08.006

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA) receptors in oxaliplatin-induced mechanical allodynia in rats. RESULTS: Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week) caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol) and memantine (1 μmol), NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t.) and ifenprodil (50 mg/kg, p.o.) significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase) but not on Day 5 (early phase). Moreover, we examined the involvement of nitric oxide synthase (NOS) as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS) inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. CONCLUSION: These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

DOI： 10.1186/1744-8069-7-8

PubMed

Language：Japanese  

DOI： 10.5649/jjphcs.36.270

J-GLOBAL

Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. Mexiletine, an orally available Na(+)-channel blocker, has widely been used in patients with chronic painful diabetic neuropathy. In the present study, we examined the effect of mexiletine on oxaliplatin-induced neuropathic pain in rats. Mexiletine (100, but not 10 and 30, mg/kg, p.o.) completely reversed both mechanical allodynia and cold hyperalgesia induced by oxaliplatin (4 mg/kg, i.p., twice a week). Lidocaine (30, but not 3 and 10, mg/kg, i.p.) also significantly relieved both pain behaviors. These results suggest that mexiletine may be effective in relieving the oxaliplatin-induced neuropathic pain clinically.

PubMed

Language：Japanese   Publisher：(一社)日本病院薬剤師会  

R-CHOP療法およびR-THP-COP療法において、ドキソルビシン(doxorubicin:以下、DXR)およびピラルビシン(pirarubicin:以下、THP)が血管外に漏出すると重大な皮膚障害を来し得る。九州大学病院消化管内科において心毒性を考慮してDXRおよびTHPを1時間で点滴静注していたが、血管外漏出が続発し、その発現頻度は10.8%(4件/37クール)であった。一方、放射線科ではDXRおよびTHPを5分以内で静脈内注射しており、血管外漏出は発現していなかった(0件/36クール)。そこで、血管外漏出の要因分析および文献調査を行い、投与方法についてカンファレンス等で協議し5分以内での静脈内注射へ変更したところ、その後血管外漏出は発現しなかった(0件/28クール)。DXRおよびTHPを5分以内で静脈内注射することで血管外漏出のリスクが著明に軽減されることが明らかとなった。(著者抄録)

J-GLOBAL

Language：Japanese   Publisher：(一社)日本病院薬剤師会  

今回我々は、がん化学療法および化学放射線療法に対する患者の理解を高めるとともに、患者自身によるセルフケアの支援を目指して、薬剤管理指導業務の際に使用する服薬指導シートの改善を行った。改善点としては、記載内容である投与スケジュール、薬効および副作用に副作用の好発時期を追加し、従来の文章中心の様式から、より視覚的に理解しやすいものに変更した。実際に、九州大学病院の放射線科病棟において薬剤管理指導業務を行う際に新様式の服薬指導シートを患者に交付し、これを基に服薬指導を行ったところ、患者および医療スタッフには大変好評であった。特に、患者には治療に対する理解が深まり、不安の軽減とともに治療への意欲向上にもつながると思われる。さらに、医師および看護師との情報交換も増加し、患者情報および薬剤情報の共有化にも有用であると考えられた。(著者抄録)

J-GLOBAL

Language：Japanese   Publisher：Japanese Society of Pharmaceutical Health Care and Sciences  

The importance of providing drug information has increased with the expansion of pharmaceutical care. In order to provide appropriate drug information to healthcare professionals, pharmacists have to understand their needs in this respect and be familiar with the procedure for answering typical questions. In the present study, we analyzed all of the questions (9,999) recorded by the drug information center of Kyushu University Hospital and the answers to them in the period from 2001 to 2007. The questions were from doctors (59.3%), pharmacists (21.5%), nurses (15.4%), and others (3.9%). The most frequent questions were on compatibility and stability of injections (18.8%), selecting drugs (13.2%), and dosage and administration (9.8%). We therefore made information on the compatibility and stability of injections available to other pharmacists via our intranet. We felt it was useful to clarify healthcare professionals' needs for drug information and develop a system enabling drug information to be used more easily.

DOI： 10.5649/jjphcs.35.161

CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JALC/00327895853?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)  

Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer, but it causes acute peripheral neuropathy (acral paresthesias triggered by exposure to cold) and chronic neuropathy (abnormal of sensory and motor dysfunction). Oxaliplatin is metabolized to oxalate and dichloro(1,2-diaminocyclohexane)platinum (Pt(dach)Cl(2)). Although the chelating of Ca(2+) with oxalate eliminated from oxaliplatin is thought as one of the reasons for the neuropathy, there is little behavioral evidence. In this study, we investigated the involvement of oxalate in the oxaliplatin-induced peripheral neuropathy in rats. Oxaliplatin (4mg/kg, i.p., twice a week) induced cold hyperalgesia/allodynia (cold-plate and acetone tests) in the early phase, and mechanical allodynia (von Frey test) in the late phase. Oxalate (1.3mg/kg, i.p., twice a week) induced the cold hyperalgesia/allodynia in the early phase, but did not induce the mechanical allodynia. On the other hand, Pt(dach)Cl(2) (3.8mg/kg, i.p., twice a week) induced the mechanical allodynia in the late phase, but did not induce the cold hyperalgesia/allodynia. The pre-administration of calcium or magnesium (0.5mmol/kg, i.v.) before oxaliplatin or oxalate prevented the cold hyperalgesia but not mechanical allodynia. However, the treatment with calcium or magnesium after the development of neuropathy could not attenuate the cold hyperalgesia or mechanical allodynia. These findings suggest the involvement of oxalate in oxaliplatin-induced cold hyperalgesia but not mechanical allodynia, and usefulness of prophylactic treatments with calcium and magnesium on the acute peripheral neuropathy.

DOI： 10.1016/j.pain.2009.09.003

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1310/hpj4307-571

Language：Japanese   Publishing type：Research paper (scientific journal)  

To provide effective and safe cancer treatment, the medical staff must form a team with patients and their family. Pharmacists have to be responsible for verifying chemotherapy prescription orders, mixing of anticancer drugs, management of adverse drug reactions, patient education, while providing drug information and participation in palliative care. To promote pharmacists who have acquired advanced knowledge and skills, The Japanese Society of Hospital Pharmacists started and educational program and established the certification of board-certified oncology pharmacy specialists (BCOPS) and board-certified pharmacists in oncology pharmacy (BCPOP). As of November 2007, 56 pharmacists were qualified as BCOPS.

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本病院薬剤師会  

我々はこれまで、抗がん剤による副作用頻度や発現時期について文献的に調査することにより、種々の化学療法レジメンに対応したがん化学療法ワークシートを作成し、確実かつ効率的な薬剤管理指導業務の実践に役立ててきた。しかしながら、この方法は通常とは異なる用量、もしくは用法の化学療法レジメン、あるいは放射線との併用療法(化学放射線療法)には対応できていなかった。今回、九州大学病院放射線科にてLow dose FP放射線併用療法が行われた16人の食道がん患者に対して薬剤管理指導業務を実施し、そのなかで副作用の発現状況について詳しく調査するとともに、予防もしくは治療のための対策など薬学的関与の必要性について検討した。また、これらのデータを基に、より効率的かつ質の高い薬剤管理指導業務を支援するための処方チェック・副作用モニタリングシートを作成した。(著者抄録)

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Pharmaceutical Health Care and Sciences  

In the present study, we evaluated the effectiveness of a new infusion set equipped with an in-line filter (5μm pore size) in removing precipitates of foreign matter forming during or after the preparation of infusion fluids. We also examined the ability of the new infusion set to prevent adverse effects associated with the intravenous injection of fluids containing crystalline precipitates in rats. The number of particles and their sizes were measured for two infusion fluids administered using a conventional infusion set without an in-line filter and the new infusion set, collecting the samples for measurement from the outlets of the respective infusion sets. One of fluids was a glycyrrhizin solution prepared from a glass ampoule injection, and the other etoposide solution prepared by diluting a preparation of this solution in a vial with saline. A number of particles (>10μm in size) were detected for both infusion fluids when administered by the conventional infusion set but none were detected in them when administered by the new infusion set. The intravenous injection of the precipitate-containing etoposide solution from the conventional infusion set to rats caused marked extravasation of plasma proteins and edema in lungs. Such adverse reactions did not occur with the new infusion set, demonstrating that it was effective in removing paniculate matter. It should thus be useful in intravascular fluid therapy from the safety point of view.

DOI： 10.5649/jjphcs.32.1228

CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JALC/00288531470?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)  

The incidence of hypersensitivity reactions is still a matter of serious concern during chemotherapy with paclitaxel, particularly in patients with ovarian cancer. We recently reported that intravenous injection of paclitaxel causes acute lung injury characterized by vascular hyperpermeability, edema and respiratory dysfunction in rats. In the present study, we investigated the influence of ovariectomy on the paclitaxel-induced acute lung injury in rats. Ovariectomy worsened paclitaxel-induced acute lung injury, which was reversed by 17beta-estradiol. The mRNA expression for endothelial nitric oxide synthase was reduced in lungs of ovariectomized rats. To determine the role for nitric oxide, we examined the effects of several agents that modulate nitric oxide concentration on the pulmonary response to paclitaxel. In ovary-intact rats, a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester exaggerated paclitaxel-induced acute lung injury, while nitric oxide donors such as sodium nitroprusside and isosorbide dinitrate attenuated the lung injury. Sodium nitroprusside was also effective in alleviating the paclitaxel-induced acute lung injury in ovariectomized rats. These findings suggest that ovariectomy enhances the susceptibility to paclitaxel hypersensitivity, in which decrease in estrogen and subsequent reduction in nitric oxide synthesis may be involved.

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：Japanese   Publisher：(一社)日本病院薬剤師会  

著者らは心臓カテーテル検査に使用される薬剤の「お薬説明書」を作成し,これを循環器内科の入院患者に用い,服薬指導を行なっている。そこで,これらを踏まえて,「お薬説明書」の有用性ならびに服薬指導の必要性について患者アンケート調査を行なった.その結果,検査前に医師より説明を受けているのにもかかわらず,服薬指導によってはじめて造影剤による遅発性副作用を知ったと答えた患者は65%もいた.また,一方で副作用に対する不安が軽減されたと答えた患者は68%いた.以上,これらのことから,心臓カテーテル検査において「お薬説明書」を用いた服薬指導は有用であると示唆された

Presentation type：Oral presentation (invited, special)  

Presentation type：Oral presentation (invited, special)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Symposium, workshop panel (nominated)  

Presentation type：Public lecture, seminar, tutorial, course, or other speech