記述言語：日本語   出版者・発行元：(一社)日本医療薬学会  

薬局薬剤師22名を対象として、服薬フォローアップを支援するためのシート(支援シート)を使用した糖尿病患者に対する服薬フォローアップについてアンケート調査を行った。対象者の薬剤師が約3ヵ月間支援シートを使用した後、服薬フォローアップの必要性の有無を判断する観点の抽出や服薬フォローアップを実施した期間を調査した。その結果、「薬剤変更(用法用量の変更を含む)」「薬剤追加」「自身の判断」の3項目が服薬フォローアップ実施の判断に必要な内容であることが示唆され、実施のタイミングは過半数が7日目前後であり、実施の手段はすべて「電話」であった。薬剤師の約4割は支援シートの適用に対して比較的肯定的であり、半数から支援シート改善に前向きな意見が得られた。本研究で作成した支援シートは、糖尿病患者を対象とした服薬フォローアップを支援することが示唆された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本医科大学医学会  

Background: The Japanese Society for Pharmaceutical Palliative Care and Sciences specializes in phar-macology in the field of palliative medicine. More than 700 board-certified pharmacists in palliative pharmacy (BCPPP) are actively involved in palliative pharmacotherapy at various hospitals and phar-macies. The purpose of this study was to determine the economic effect of pharmaceutical interventions by BCPPPs. Methods: This multicenter retrospective study included 27 medical centers and analyzed the medical economic effect of interventions by BCPPPs (17 pharmacists) and non-BCPPPs (24 pharmacists) on patients using medical narcotics for cancer pain in September 2021. Results: The percentage of patients who received a pharmaceutical intervention and whose drug costs were reduced by pharmacist intervention was significantly higher in the BCPPP group than in the non-BCPPP group. Although there was no significant difference between the two groups in drug cost reduction per patient per month (BCPPP group: $0.89 [−$64.91 to $106.76] vs. non-BCPPP group $0.00 [−$1,828.95 to $25.82]; P = 0.730), the medical economic benefit of pharmacist intervention in avoiding or reducing adverse drug reactions was higher in the BCPPP group ($103.18 [$0.00 to $628.03]) than in the non-BCPPP group ($0.00 [$0.00 to $628.03]) (P = 0.070). The total medical economic benefit―the sum of these―was significantly higher in the BCPPP group ($88.82 [−$14.62 to $705.37]) than in the non-BCPPP group ($0.66 [−$1,200.93 to $269.61]) (P = 0.006). Conclusion: Pharmacological intervention for patients with cancer using medical narcotics may have a greater medical economic benefit when managed by BCPPPs than by non-certified pharmacists in Japan.

DOI： 10.1272/jnms.jnms.2024_91-105

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CiNii Research

記述言語：英語   出版者・発行元：日本医科大学医学会  

がん性疼痛に対して医療用麻薬を使用したがん患者に対する緩和薬物療法認定薬剤師(BCPPP)による薬学的介入の経済的効果を明らかにした。本研究は27施設が参加した多施設共同後ろ向き研究であり、BCPPP 17名(経験年数中央値17年)と非BCPPP 24名(同10年)が参加した。薬剤師の介入によって薬剤費が削減された患者の割合は、BCPPP群が20.0%、非BCPPP群が5.3%で有意差が認められた。患者1人の1ヵ月間の薬剤費削減額は両群間で有意差はなかったが、薬剤師の介入による副作用の回避・削減による医療経済的便益はBCPPP群が非BCPPP群よりも高かった。医療経済的便益の合計は、BCPPP群が非BCPPP群よりも有意に高かった。

掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

<b><i>Introduction:</i></b> Anticancer drug-induced stomatitis can affect a patient’s quality of life and the continuation of drug treatment. Although there have been reports of the occurrence of stomatitis associated with anticancer agents in clinical trials, few Japanese participants have been enrolled in clinical trials and have not been sufficiently investigated. In addition, there has been little attention on research on anticancer drugs associated with stomatitis by patient stratification with different carcinogenic sites. Therefore, the aim of this study was to determine the disproportionality associated with stomatitis for various types of anticancer drugs in different types of cancer patients using the Japanese Adverse Drug Event Report (JADER) database. <b><i>Methods:</i></b> The aim of this study was to identify the disproportionality of stomatitis by analyzing the type of anticancer drug and cancer patients using the Japanese Pharmacovigilance Database. Data obtained from spontaneous reports of adverse events with more than 10 stomatitis outbreaks reported in the JADER database between April 2004 and March 2023 were analyzed. The safety signal for an adverse event was defined as the lower limit of the 95% confidence interval of the reported odds ratio of >1. <b><i>Results:</i></b> There were 6,178 reports of drugs associated with stomatitis. Among these, 41 drugs were suggested to be associated with stomatitis, and 41 drugs were detected as signals. These drugs were classified based on their efficacy: antipyrimidines (six drugs), folate metabolism antagonists (three drugs), alkylating agents (four drugs), platinum (three drugs), topoisomerase inhibitors (three drugs), microtubule inhibitors (three drugs), mammalian target of rapamycin (mTOR) inhibitors (two drugs), kinase inhibitors (seven drugs), anti-growth factor antibodies (five drugs) immune checkpoint inhibitors (one drug), and others (four drugs). <b><i>Conclusion:</i></b> The drugs that may be associated with stomatitis were cell cycle-dependent drugs, epidermal growth factor receptor-tyrosine kinase inhibitors, and mTOR inhibitors. Moreover, this study suggested that anti-growth factor antibodies and immune checkpoint inhibitors may be associated with stomatitis development.

DOI： 10.1159/000535331

記述言語：英語   出版者・発行元：Cancer Diagnosis and Prognosis  

Background/Aim: Rash is a common adverse event (AE) observed during cytarabine and idarubicin induction therapy in patients with acute myeloid leukemia (AML). Previous studies have highlighted the challenge in predicting the onset and duration of rash. This study aimed to determine the factors that affect the onset of rash in patients receiving induction therapy for AML. Patients and Methods: This retrospective study involved 97 patients with AML who received induction chemotherapy with cytarabine and idarubicin at the Department of Hematology, Kyushu University Hospital between January 2008 and June 2022. The factors associated with rash were identified through a multivariate stepwise logistic regression analysis. Subsequently, the patient’s characteristics were compared between those with risk factors and those without risk factors using a matched pair analysis. Results: Pre-existing leukopenia [odds ratio (OR)=3.294; 95% confidence interval (CI)=1.272-8.531] and good performance status (PS=0) (OR=2.717; 95%CI=1.087-6.792) were significant risk factors for rash development. Conversely, the matched pair analysis indicated that patients with pre-existing leukopenia, excluding those with a PS score of 0, exhibited a significantly (p=0.015) higher incidence of rash than those without it. Conclusion: Both multivariate logistic regression analysis and matched pair analysis identified pre-existing leukopenia as a primary risk factor for rash development associated with cytarabine and idarubicin chemotherapy.

DOI： 10.21873/cdp.10372

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記述言語：英語   出版者・発行元：日本医科大学医学会  

大規模副作用データベースであるJapanese Adverse Drug Event Report(JADER)を用いて、日本の非がん患者におけるオピオイド関連呼吸抑制(RD)を調査した。2004年4月～2020年2月にJADERに記録されたデータを解析した。2020年2月までに日本で承認された20種のオピオイドについてRDのオッズ比を算出した。さらに、非がん性慢性疼痛(CNCP)に対するオピオイドの1日投与量と作用発現時間を解析した。1639417症例のうち、非がん患者でRDが報告された薬剤は1883剤であった。20種のオピオイドのうち、12種のオピオイドで非がん患者のRDが報告された。RDが報告された22通りのオピオイドと投与経路の組み合わせのうち、ブプレノルフィン経皮投与とトラマドール/アセトアミノフェン経口投与はCNCPに対して承認されており、高齢患者で報告例が多い傾向があった。この2剤の1日投与量中央値は、それぞれ経口モルヒネ換算で10.0mgおよび22.5mg、RD出現までの期間中央値はそれぞれ6.5日および4.0日であり、症例の75%は投与開始後20～40日以内に報告された。

記述言語：英語   出版者・発行元：(一社)糖化ストレス研究会  

ブドウの品種、産地、醸造方法の違いにより抗糖化作用が強いワインを選出し、そのワインを摂取することでヒト血中終末糖化産物(AGEs)蓄積抑制作用に影響がみられるか調べた。本研究では、アルコール摂取が可能な20歳以上65歳未満の男女48名を対象とする前向きクロスオーバー非盲検無作為化比較試験を行った。基礎研究では、ヒト血清アルブミン(HSA)-グルコース糖化モデルに各種ワインを添加し、蛍光AGEs産生量を測定することで糖化抑制効果を評価した。参加者には、基礎研究で抗糖化作用が強かったワインまたはミネラルウォーターのどちらか1種類を週6日、1日125mLずつ4週間継続して摂取させた。摂取前と摂取後の計4回、体内のAGEs蓄積レベルとストレス値を測定した。AGEs蓄積に影響する生活に関するアンケート調査を実施した。アンケート結果の回答率が50%未満の9名および測定会に1回以上欠席した6名を除外した。ワイン摂取群ではAGEs値の低下が見られ、ミネラルウォーター摂取群ではAGEsの上昇が見られたが、有意差はなかった。第2週～5週群(6月上旬～7月中旬)と第8週～11週群(7月下旬～9月上旬)の比較では、ワイン摂取前後のAGEs値は強い減少傾向がみられた。女性はワイン摂取後のAGEsが低下する傾向がみられた。第8週～11週群の女性ではワインを摂取群のAGEsが有意に低下した。

記述言語：英語   出版者・発行元：日本医科大学医学会  

日本緩和医療薬学会に所属する薬剤師を対象に、2022年2～3月にオンラインアンケート調査を行い、緩和薬物療法を受ける患者の身体症状や精神症状に対する服薬指導の状況を調査した。また、緩和薬物療法認定薬剤師と非認定薬剤師の服薬指導の実態を比較した。3854名に調査を依頼し、緩和薬物療法認定薬剤師(認定群)123名(58.9%)と非認定薬剤師(非認定群)86名(41.1%)の計209名の回答を分析した。認定群は非認定群よりも病院所属率、薬剤師経験年数、緩和ケアチームへの所属率が有意に高かった。疼痛緩和に関する4項目、疼痛以外の症状緩和に関する全項目、精神症状緩和に関する項目については、認定群の方が服薬指導を行う頻度が高かった。患者のQOLの向上につながる緩和薬物療法への関与については、認定群が非認定群よりも高い評価を得ていた。緩和薬物療法認定薬剤師は、非認定薬剤師と比較して、より積極的に介入し、より幅広い緩和薬物療法を提供していることが示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Anticancer Research  

Background/Aim: Adverse events (AEs) must be managed during cancer therapy. We had previously developed a medication guidance sheet (MGS) to monitor AEs after conditioning therapy with allogeneic hematopoietic stem cell transplantation (HSCT). However, it remains unclear whether this sheet can accurately predict the type, onset, and duration of AEs in clinical practice. In this study, we evaluated the clinical utility of the original MGS in patients receiving total body irradiation (TBI) and cyclophosphamide (CY). Patients and Methods: Fifty-eight patients who underwent TBI/CY were included. The types, onsets, and durations of AEs observed during real monitoring were compared with those listed in the original MGS. Results: A total of 361 subjective AE symptoms were observed, all of which were predictive, as listed in the MGS. However, the durations of several AEs were longer than expected. Thus, the prediction accuracy for all AEs was 67.0%. The accuracy rate was the lowest for anorexia (6.7%), followed by diarrhea (42.6%), and nausea/vomiting (55.6%). Acute graft versus host disease (GVHD) most likely caused the prolongation of AEs. Subsequently, the original MGS was revised to account for the possible occurrence of acute GVHD. Conclusion: When monitoring AEs in patients receiving a TBI/CY conditioning regimen for HSCT, the involvement of acute GVHD-associated AEs should be considered. In this respect, the present modified MGS is particularly useful for rapid and accurate monitoring of AEs.

DOI： 10.21873/anticanres.16596

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cardiac adverse events (CAEs) have become a concern as serious adverse events of nilotinib administration. No reports have described the incidence of CAEs associated with nilotinib in Japanese patients. OBJECTIVES: Thus, we conducted this study to evaluate the risk of nilotinib-induced CAEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHOD: We analysed data for the period between April 2004 and March 2022. Data on CAEs were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio (ROR). RESULTS: We analysed 2,021,907 reports and identified 3,545 reports of AEs caused by nilotinib. Of these, 511 reports involved CAEs. Signals were detected for 19 CAEs. Of these, electrocardiogram QT prolonged was the most frequently reported (30.9%). Fatal outcomes were observed in eight AEs: cardiac failure, atrial fibrillation, acute myocardial infarction, pericardial effusion, myocardial infarction, cardiac arrest, pericarditis, and cardiac tamponade. Of these, acute myocardial infarction, myocardial infarction, pericarditis, and cardiac tamponade exhibited mortality rates >10%. A histogram of median times to onset showed nilotinib-associated AEs occurring 3-485 days after nilotinib administration. CONCLUSIONS: We focused on CAEs caused by nilotinib as post-marketing AEs. Some cases resulted in serious outcomes. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but for a long period of time.

DOI： 10.1159/000533325

PubMed

担当区分：最終著者   記述言語：英語  

Background Pembrolizumab has been widely used in patients since its release, but detailed information on lung-specific adverse events (AEs) from post-marketing monitoring has not been reported. Objectives This study was undertaken to determine the risk of pembrolizumab-induced lung AEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. Method We analyzed data for the period between April 2004 and March 2022. Data on lung AEs were extracted and the relative risks of AEs were estimated using reporting odds ratios. Results We analyzed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab, including 3,004 lung AEs. Signals were detected for 14 lung AEs. Interstitial lung disease was the most frequently reported (62.3%) and included fatal cases. A histogram of median time to onset showed occurrence from 2 to 73 days, but some cases of interstitial lung disease occurred even more than 2 years after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, respiratory failure, and pneumonia aspiration. Conclusions This study focused on lung AEs caused by pembrolizumab as post-marketing AEs. Some cases could potentially involve serious outcomes, so patients should be monitored for signs of AE onset not only at the start of administration, but also over an extended period, especially for interstitial lung disease.

DOI： 10.1159/000533302

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Pharmacological Sciences  

Cachexia is a common cancer complication and is associated with weight loss and anorexia. In this study, we investigated the ameliorating effects of cystine and theanine on cancer cachexia using a mouse model. In mice carrying the colon cancer cell line C-26, there was a suppression of body weight increase and reduction in both internal fat and lower limb muscles. Repeated cystine and theanine administration significantly prevented weight loss, internal fat loss, lower limb muscle loss, and serum IL-6 increase in the cachexia model. These results suggested that cystine and theanine may be effective in ameliorating cancer cachexia.

DOI： 10.1016/j.jphs.2023.04.008

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記述言語：英語   出版者・発行元：(公社)日本薬理学会  

癌悪液質(CC)マウスモデルを用いて、シスチンとテアニンの併用(CT)がCCに及ぼす改善効果を、アナモレリン(AM)と比較した。結腸癌細胞株C-26担癌マウスモデルにて、CT群、AM群、無処置対照群のいずれでも体重増加が抑制され、精巣上体脂肪などの内部脂肪とヒラメ筋などの下肢筋肉の両者が減少した。CTの反復投与によるCT群では、対照群に比べて体重減少、内部脂肪減少、下肢筋肉減少、血清IL-6増加が有意に抑制され、その効果はAM群と同程度であった。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Anticancer Research  

Background/Aim: For quick and accurate monitoring of potential adverse events (AEs) during concurrent chemotherapy, we had previously developed innovative medication instruction sheets (MIS) for a variety of chemotherapy regimens. However, it is still unclear whether these sheets correctly predict the type and time course of the onset and recovery of AEs. Therefore, we monitored AEs in patients with acute myeloid leukemia (AML) receiving high-dose cytarabine (HD-AraC) using the original MIS. Patients and Methods: Patients who received HD-AraC following remission induction chemotherapy were included in this study. Data obtained from AE monitoring were evaluated, and the original MIS was modified as appropriate. Results: Among 41 patients, a total of 203 AEs (139 non-hematological and 64 hematological) were observed after chemotherapy. By contrast, all but one patient (97.6%) experienced 102 AEs (43 nonhematological and 59 hematological) before chemotherapy. The AEs that appeared after chemotherapy were all predicted items described in the original MIS; however, their onset and duration were not consistent with the predicted data, in which the prediction accuracy was 69.1% for non-hematological AEs and 1.6% for hematological events. Based on these monitoring data, the original MIS was revised, which led to an increase in the prediction accuracy to 94.2% for nonhematological events and 100% for hematological events. Conclusion: Preexisting AEs should be considered when preparing MIS for consolidation therapy with HD-AraC. The modified MIS based on AE monitoring exhibited a sufficiently high prediction accuracy.

DOI： 10.21873/anticanres.16508

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: Intoroduction: Azacitidine is a useful drug for myelodysplastic syndromes and acute myeloid leukemia. In clinical trials, hematologic toxicity, infection have been observed as adverse events (AEs) of this drug. However, information on the time to onset of high-risk AEs and subsequent outcomes, as well as differences in the frequency of AEs due to the route of administration is lacking. In this study, we investigated azacitidine-induced AEs comprehensively using the Japanese Adverse Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency, with disproportionate analysis of AE incidence trends, time to onset, and subsequent outcomes. In addition, we analyzed the differences in AEs by route of administration and the number of days until the occurrence of AEs and generated hypotheses. METHODS: The study used JADER data reported from April 2004 to June 2022. Risk estimation was conducted using reported odds ratio (ROR). A signal was detected when the lower limit of the 95% confidence interval of the calculated ROR was ≥ 1. RESULTS: A total of 34 signals were detected as AEs due to azacitidine. Among them, 15 were hematologic toxicities, and 10 were infections, which demonstrated a particularly high rate of death. Signals of AEs such as tumor lysis syndrome (TLS) and cardiac failure, which have been described in case reports, were also detected, and the rate of death after onset was high. In addition, more AEs generally occurred within the first month of treatment. DISCUSSION/CONCLUSION: The results of this study suggest that more attention should be paid to cardiac failure, hematologic toxicity, infection, and TLS. Because in clinical trials have discontinued treatment due to serious AEs before the therapeutic effect became apparent, appropriate supportive care, dose reduction, and drug withdrawal are important for the continuation of treatment.

DOI： 10.1159/000531390

PubMed

記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study was conducted to examine times to onset, incidence rates, and outcomes of nivolumab-induced lung adverse events (AEs), using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung AEs were extracted, and relative risks of AEs were estimated using the reporting odds ratio. We analysed 5,273,115 reports and found 18,721 reports of nivolumab-related AEs, including 3084 lung AEs. Signals were detected for nine lung AEs: interstitial lung disease; pneumonitis; lung disorder; organising pneumonia; pleural effusion; pneumonia aspiration; pneumonia bacterial; radiation pneumonitis; and infectious pleural effusion. Among these, interstitial lung disease was the most frequently reported (68.7%) and included some fatal cases. A histogram of median times to onset showed AEs occurring from 34 to 79 days after the first dose, but some cases occurred even more than one year after starting administration. In conclusion, we focused on lung AEs caused by nivolumab as post-marketing AEs. Some cases could potentially involve serious outcomes, particularly in interstitial lung disease. Patients should be monitored for signs of the development of these AEs not only at the start of administration, but also over an extended time.

DOI： 10.1038/s41598-023-35602-w

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：In Vivo  

Background/Aim: To monitor adverse events rapidly and accurately during combination chemotherapy, we established an innovative medication instruction sheet (MIS) including cytarabine and idarubicin induction therapy. However, it is unclear whether this MIS allows for the accurate prediction of adverse events and their onset timing in a clinically significant manner. We therefore evaluated the clinical usefulness of our MIS for monitoring adverse events. Patients and Methods: Patients who received cytarabine and idarubicin induction therapy for acute myeloid leukemia (AML) at the Department of Hematology, Kyushu University Hospital between January 2013 and February 2022 were included. The real-world clinical data were compared to the MIS to determine the accuracy of the MIS for predicting the onset and duration of adverse events in patients with AML during induction chemotherapy. Results: Thirty-nine patients with AML were included in this study. Overall, 294 adverse events were noted, all of which were predicted items in the MIS. Among the 192 non-hematological adverse events, 131 (68.2%) occurred during a similar period as that listed in the MIS, whereas among the 102 hematological adverse events, 98 (96.1%) appeared earlier than expected. For the non-hematological events, the onset and duration of elevated aspartate aminotransferase levels and nausea/vomiting coincided well with those listed in the MIS, whereas the predictive accuracy for rashes was the lowest. Conclusion: Hematological toxicity was not predicted because of the bone marrow failure associated with AML. Our MIS was useful for rapidly monitoring non-hematological adverse events in patients with AML receiving cytarabine and idarubicin induction therapy.

DOI： 10.21873/invivo.13164

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Nivolumab has been used for the treatment of various types of cancers and has achieved improvements in overall survival. However, nivolumab can cause a variety of adverse events (AEs). Among these, cardiac-specific AEs have received little attention in clinical trials, despite their life-threatening potential. OBJECTIVE: The present study aimed to determine the risk of nivolumab-induced cardiac AEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHODS: We analyzed data for the period between April 2004 and March 2021. Data on cardiac AEs were extracted and relative risk of AEs was estimated using the reporting odds ratio (ROR). RESULTS: We analyzed 1,772,494 reports and identified 18,721 reports of AEs caused by nivolumab. Of these, 409 reports involved cardiac AEs. Signals were detected for four cardiac AEs: myocarditis; pericardial effusion; pericarditis; and immune-mediated myocarditis. Among these, myocarditis was the most frequently reported (35.0%) and included fatal cases. A histogram of times to onset showed nivolumab-associated AEs occurring 41-127 days after starting administration, with outlier cases of myocarditis or pericardial effusion occurring after more than one year, both with catastrophic consequences. CONCLUSION: This study focused on cardiac AEs caused by nivolumab as post-marketing AEs. Myocarditis and pericardial effusion have been associated with some fatal cases after administration of nivolumab. Patients should be monitored for signs of onset for these AEs, not only at the start of administration, but also over an extended period after nivolumab administration.

DOI： 10.1007/s40261-023-01246-x

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment-induced severe immune-related hepatitis (ir-hepatitis) and the efficacy and safety of MMF. METHODS: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records. RESULTS: The ratio of male to female patients was 7:1, and the median age was 60 years (27-72 years). There were five and two cases of kidney cancer and malignant melanoma, respectively, and one case of lung cancer. The median number of days until MMF administration in addition to systemic corticosteroid therapy after the onset of ir-hepatitis was 14.5 (2-42). The patients were categorized as four "good responders" who showed an improvement in the liver function tests following MMF treatment and four "poor responders" who did not. Furthermore, the time from the onset of ir-hepatitis to initial MMF administration was significantly shorter in good responders (median 3 days, range 2-15 days) than in poor responders (median 25.5 days, range 14-42 days) (P = 0.042). No significant intergroup difference was observed in other clinical factors. No serious adverse events caused by MMF were observed in any case. CONCLUSIONS: According to these findings, early recognition of corticosteroid refractoriness and the use of MMF may be beneficial in patients with ir-hepatitis.

DOI： 10.1002/jgh3.12868

PubMed

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Pomalidomide is an immunomodulatory drug that is used to treat multiple myeloma. We examined the time-to-onset and outcome of lung adverse events (LAEs) related to pomalidomide in Japanese patients based on information obtained from the spontaneous reporting system of the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency. PATIENTS AND METHODS: We analyzed adverse events (AEs) reports recorded between April 2004 and March 2021 from JADER. Data on LAEs were extracted, and the relative risk of AEs was estimated using the reporting odds ratio and 95% confidence interval. We analyzed 1,772,494 reports and identified 2,918 reports of AEs caused by pomalidomide. Of these, 253 LAEs were reportedly associated with pomalidomide. RESULTS: Signals were detected for five LAEs: pneumonia, pneumocystis jirovecii pneumonia, bronchitis, pneumonia bacterial, and pneumonia pneumococcal. Pneumonia was the most frequently mentioned condition (68.8%). The median time-to-onset of pneumonia was 66 days, but some cases of pneumonia occurred as late as 20 months after the start of administration. Fatal outcomes were observed in two of the five AEs wherein signals were detected and were due to pneumonia and bacterial pneumonia. CONCLUSION: Serious outcomes can occur after pomalidomide administration. It has been suggested that these LAEs occur relatively early after pomalidomide administration. Since some situations can result in fatal consequences, patients should be monitored for the emergence of these AEs over a prolonged period of time, especially for pneumonia.

DOI： 10.21873/invivo.13168

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis. PATIENTS AND METHODS: We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data. RESULTS: The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs. CONCLUSION: The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

DOI： 10.21873/invivo.13085

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Opioid-induced respiratory depression (RD) is a potentially life-threatening adverse drug event. This study used the Japanese Adverse Drug Event Report (JADER) database to investigate the profile of opioid-related RD in non-cancer patients. METHODS: We analyzed data recorded in the JADER database between April 2004 and February 2020, which were downloaded from the Pharmaceutical and Medical Devices Agency website. Reporting odds ratios for RD were calculated for the 20 opioids approved in Japan, and daily dose and onset time were further analyzed for opioids used in chronic non-cancer pain (CNCP). RESULTS: Among the opioids, RD adverse event signals were detected for 22 combinations of opioids and administration routes in non-cancer patients. Of these combinations, transdermal buprenorphine and oral tramadol/acetaminophen were approved for CNCP and tended to be reported more frequently in elderly patients. The median daily doses of transdermal buprenorphine and oral tramadol/acetaminophen were 10.0 and 22.5 mg of daily oral morphine equivalent doses, respectively, which are within the standard range for starting dosage. The median time-to-onset of transdermal buprenorphine and oral tramadol/acetaminophen was 6.5 and 4.0 days, respectively, and 75% of cases were reported within 20 to 40 days after the start of treatment. The hazard type for both opioids was classified as early failure. CONCLUSIONS: Our findings suggest that elderly CNCP patients should be closely monitored after the start of opioid treatment, especially during the first week and, if possible, for 1 month, even if starting doses are within ranges recommended by the manufacturer and guidelines.

DOI： 10.1272/jnms.JNMS.2023_90-612

PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: In Japan, the involvement of hospital pharmacists in inappropriate medications (IMs) practices has not been sufficiently reported. Therefore, this prospective study described the interventions of hospital pharmacists in discontinuing inappropriate drugs or reducing drug doses. Methods: We conducted a prospective, multicenter, observational study to investigate the intervention of hospital pharmacists in inappropriate prescriptions for inpatients in September 2018. Fifty pharmacists from 45 hospitals in Japan participated in this study. IMs were defined as medications that pharmacists deemed inappropriate for patient treatment. The subjects of the study were patients who interacted with the participating pharmacists. Results: During the study period, the median number of beds in hospitals where the 50 participating pharmacists worked was 380, and the average number of beds for which the pharmacists were responsible was 49. The enrolled hospital pharmacists recommended that doctors discontinue or reduce the doses of their regular drugs for 347 out of 1,415 (24.5%) patients. Among the 391 pharmacists' recommendations to reduce IMs for 347 patients, physicians accepted 368 (94.1%) recommendations, and 523 drugs were discontinued as a result. Pharmacist intervention also led to improvements in hypnotic sedation, delirium, and hypotension. The most common reasons for IMs identified by pharmacists were "long-term administration of irresponsible or aimless medications" (44.5%), "adverse effects caused by medications" (31.5%), and "medications-mediated duplication of the pharmacological effect" (15.3%). Approximately 90% of pharmacists' suggestions to reduce medications were accepted for each reason. The average number of regular medications used by patients involved in drug reduction was 8.2, and the average number of medications reduced was 1.7. A sub-analysis showed that patients using opioids tended to take more medications, and these patients were able to reduce the amount of medications taken. Interventions by pharmacists certified in palliative pharmacies tended to reduce adverse drug events. Conclusion: This was the first multicenter prospective observational study conducted in Japan to demonstrate hospital pharmacist intervention's effectiveness in promoting appropriate prescription and, consequently, a reduction in the number of medications in use and polypharmacy.

DOI： 10.3389/fphar.2023.1195732

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Lenalidomide (LND) is an oral antineoplastic agent used in the treatment of various malignant hematologic diseases, including multiple myeloma. Major adverse events of LND include myelosuppression, pneumonia, and thromboembolism. Thromboembolism is an adverse drug reaction (ADR) associated with poor outcomes, therefore anticoagulants are administered prophylactically. However, LND-induced thromboembolism has not been clearly characterized from clinical trials. The purpose of this study was to evaluate the incidence, timing, and outcome details of thromboembolism caused by LND using the JADER (Japanese Adverse Drug Event Report) database. PATIENTS AND METHODS: ADRs due to LND reported from April 2004 to March 2021 were selected. Data on thromboembolic adverse events were analyzed and relative risks were estimated using reported odds ratios (RORs) and 95% confidence intervals (CIs). In addition, the time of onset and outcome of thromboembolism were analyzed. RESULTS: There were 11,681 adverse events attributed to LND. Of these, 306 were thromboembolisms. The most frequently reported thrombosis with the highest ROR was deep vein thrombosis (DVT) (165 cases, ROR=7.12, 95%CI=6.09-8.33). The median onset of DVT (quartiles, 25-75%) was 80 (28-155) days. The parameter value (β) was 0.87 (0.76-0.99), suggesting the onset of DVT early in treatment. The prognosis of DVT due to LND was recovery and remission in 34% and 43% of patients, respectively, but 7.9% did not recover. CONCLUSION: DVT is the most frequent thromboembolism in LND, and early treatment is important.

DOI： 10.21873/invivo.13201

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The efficacy of ponatinib was demonstrated in patients resistant or intolerant to prior BCR-ABL tyrosine kinase inhibitors. However, cardiac adverse events (CAEs) have become a concern as a serious side effect of ponatinib administration. No reports have described the incidence of CAEs associated with ponatinib in Japanese patients. Thus, this study aimed to determine the risk of ponatinib-induced CAEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHODS: We analyzed data for the period between April 2004 and March 2021. Data on CAEs were extracted, and relative risk of AEs was estimated using the reporting odds ratio. RESULTS: We analyzed 1,772,494 reports and identified 1,152 reports of AEs caused by ponatinib. Of these, 163 CAEs were reportedly associated with ponatinib. Signals were detected for thirteen CAEs: hypertension, cardiac failure, acute cardiac failure, atrial fibrillation, increased blood pressure, coronary artery stenosis, myocardial infarction, angina pectoris, pulmonary hypertension, prolonged QT on electrocardiography, cardiomyopathy, cardiac dysfunction, and acute myocardial infarction. Among these, hypertension was the most frequently reported AE (27.6%). A histogram of times to onset showed occurrence from 4.5 to 150.5 days. DISCUSSION/CONCLUSION: Hypertension, cardiac failure, coronary artery stenosis, and myocardial infarction could potentially result in serious outcomes and some cases occurred earlier or even more than 1 year after starting administration. Patients should be monitored for signs of the onset of these AEs not only at the start of ponatinib administration but also over the longer term.

DOI： 10.1159/000529768

PubMed

記述言語：英語  

BACKGROUND: Proteasome inhibitors (PIs) are standard treatments for multiple myeloma (MM). The risk of cardiac adverse events (CAEs) with PIs has been documented with bortezomib and carfilzomib; however, only a few studies have been reported on ixazomib. Furthermore, the effects of concomitant medications including dexamethasone and lenalidomide remain unclear. OBJECTIVES: This study aimed to determine the safety signals of adverse events related to CAEs, the effect of concomitant medications, the time to the occurrence of CAEs, and the incidence of fatal clinical outcomes after the occurrence of CAEs for three PIs using the US Pharmacovigilance database. METHODS: We examined 1,567,240 cases of 231 drugs registered as anticancer drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1997 to March 2021. We compared the odds of developing CAEs between patients who received PIs and those who received non-PI anticancer drugs. RESULTS: Bortezomib treatment resulted in significantly higher reporting odds ratios (RORs) for cardiac failure, cardiac failure congestive, and atrial fibrillation. Carfilzomib treatment resulted in significantly higher RORs for cardiac failure, congestive cardiac failure, atrial fibrillation, and QT prolonged. However, no adverse event CAE signals were observed with ixazomib treatment. A signal was detected for the safety of cardiac failure with bortezomib or carfilzomib, regardless of the presence or absence of concomitant medications. Safety signals for cardiac failure congestive with bortezomib and for cardiac failure congestive, atrial fibrillation, and QT prolonged with carfilzomib were observed only with dexamethasone combination therapy. Co-administration of lenalidomide and its derivatives did not affect the safety of bortezomib and carfilzomib. CONCLUSION: We identified CAE safety signals for bortezomib and carfilzomib exposure when compared with 231 other anticancer agents. The safety signal for developing cardiac failure for both the drugs did not differ between patients with and without concomitantly administered medications.

DOI： 10.1159/000529341

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Lenalidomide (LND) is an oral anticancer drug used to treat various malignant hematologic diseases, including multiple myeloma. The most common adverse events with LND are myelosuppression, thrombosis and pneumonia. Myelosuppression is reversible, and thrombosis can be treated with prophylactic administration of antithrombotic drugs. Pneumonia is less common and its incidence profile in clinical studies is unclear. This study aimed to evaluate the incidence and onset timing of LND-related lung toxicity and outcome details using the Japanese Adverse Drug Event Report (JADER) database. PATIENTS AND METHODS: Adverse events with LND reported between April 2004 and March 2021 were selected. Data on lung adverse drug reactions (ADRs) were analyzed, and safety signals were estimated using reported odds ratios (RORs) and 95% confidence intervals (CIs). We also estimated the timing of onset of lung toxic signs. RESULTS: A total of 10,929 ADRs were attributed to LND. Of these, 908 were lung toxicities. The most frequently reported ADRs with significantly high RORs were pneumonia (559 cases, ROR=3.89, 95% CI=3.57-4.24) and bacterial pneumonia (38 cases, ROR=2.02, 95% CI=1.46-2.78). Median onset of pneumonia and bacterial pneumonia were 84 and 74 days, respectively. Prognoses of patients who received LND and had pneumonia and bacterial pneumonia were poor, with 10-20% non-recovery and deaths. CONCLUSION: The findings indicate that pneumonia and bacterial pneumonia, among all LND-related lung toxicities, may be associated with immunosuppression, suggesting the importance of monitoring respiratory symptoms within the first 3 months of treatment.

DOI： 10.21873/anticanres.16101

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Toxics  

The anticancer drug, paclitaxel, is widely used for ovarian, breast, non-small cell lung, and gastric cancers; however, it induces peripheral neuropathy as a side effect. There is insufficient evidence-based prophylaxis, and new prophylaxis and treatment methods are required. We examined the effect of α1-receptor antagonists on paclitaxel-induced peripheral neuropathy using Sprague-Dawley rats and a large adverse event database. The repeated administration of doxazosin or tamsulosin significantly reduced the response threshold to paclitaxel administration in animal models. In the sciatic nerve tissue, axonal degeneration and myelopathy were significantly suppressed. Furthermore, an analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database suggested that the group using α1 inhibitors showed a lower reporting rate for paclitaxel-related peripheral neuropathy than the group that did not use these inhibitors (odds ratio (95% confidence interval): tamsulosin 0.21 (0.08–0.56), p < 0.01, doxazosin 0.41 (0.10–1.65), p = 0.195; any α1 receptor antagonist 0.54 (0.38–0.76), p < 0.01). Thus, doxazosin and tamsulosin may inhibit the development of paclitaxel-induced peripheral neuropathy by suppressing neurodegeneration, particularly axonal degeneration and myelopathy.

DOI： 10.3390/toxics10110669

Web of Science

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.

DOI： 10.1007/s12032-022-01805-w

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study was undertaken to determine the risk of bevacizumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analysed 5,273,115 reports and identified 20,399 reports of AEs caused by bevacizumab. Of these, 1679 lung toxicities were reportedly associated with bevacizumab. Signals were detected for nine lung toxicities. A histogram of times to onset showed occurrence from 35 to 238 days, but some cases occurred even more than one year after the start of administration. Approximately 20% of AEs were thromboembolic events. Among these, pulmonary embolism was the most frequently reported and fatal cases were also reported. The AEs showing the highest fatality rates were pulmonary haemorrhage, pulmonary infarction, and pulmonary thrombosis. In conclusion, we focused on lung toxicities caused by bevacizumab as post-marketing AEs. Some cases could potentially result in serious outcomes, patients should be monitored for signs of onset of AEs not only at the start of administration, but also over a longer period of time.

DOI： 10.1038/s41598-022-19887-x

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cyclosporine is widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events profiles associated with cyclosporine in transplant patients using a spontaneous reporting system database. METHODS: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database, with the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event. RESULTS: The database comprised 3,327, 958, and 956 reports associated with cyclosporine in the kidney, stem cell, and heart transplant patients, respectively. Infectious and renal disorders were commonly detected in these transplant patients. The signal scores of cyclosporine for toxic nephropathy were noteworthy in the kidney (ROR: 15.1, 95% CI: 11-20.8) and stem cell (ROR, 216; 95% CI, 29.3-1593) transplantation. Cyclosporine in heart transplantation was strongly associated with gastric cancer (ROR, 39.4; 95% CI, 16.7-93.2), but not kidney or stem cell transplantation. CONCLUSION: It was suggested that there is a diversity in the strength of the association between cyclosporine and adverse events in the kidney, stem cell, and heart transplantation. Our results may provide useful information for treatment with cyclosporine, although further research with more data is needed.

DOI： 10.7759/cureus.29383

PubMed

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Continuing education is essential for pharmacists to acquire latest knowledge. Our previously established educational program for pharmacists on the systematic and extensive palliative care of cancer patients was evaluated for its educational effectiveness in one urban prefecture. However, whether the same learning effect can be achieved when a program is expanded from one urban prefecture to multiple rural prefectures is unclear. In this study, we examined whether the continuing education program would be useful to pharmacists, even if the scale was expanded. EDUCATIONAL ACTIVITY AND SETTING: With the aim of correcting educational disparities in the region, pharmacists living in nine prefectures in the Kyushu area underwent a systematic and extensive palliative care educational program for six days (with 24 topics in total). They were administered a questionnaire before and after each topic to evaluate their level of understanding. FINDINGS: The level of understanding of the 24 topics in the program that palliative care pharmacists underwent, from "basic knowledge" to "clinical application," significantly improved (P < .01). SUMMARY: The educational program for pharmacists is useful even when implemented on a larger scale. We believe that our efforts are important for improving community-based care.

DOI： 10.1016/j.cptl.2022.07.034

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/life12091355

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Juvenile idiopathic arthritis (JIA) is a systemic inflammatory disease of childhood onset. The purpose of this study was to clarify the frequency of adverse events caused by drugs used in JIA treatment and characterize their safety profiles using a spontaneous reporting system database. We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports on drugs used for the treatment of JIA and which were submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for reports on each adverse event were calculated. A total of 5,748 reports were identified in the treatment of JIA, in which 35 different drugs were involved. Adverse events by drugs in JIA were frequently reported in females (64.3%) and in those younger than 10 (61.2%). Among the most frequently reported drugs, prednisolone (36.8%) and tocilizumab (36.0%) were predominant. Prednisolone was significantly correlated with hematophagic histiocytosis (ROR, 1.37; 95% CI, 1.18 - 1.61). Tocilizumab was associated with a high ROR for pneumonia (ROR, 8.61: 95% CI, 5.81 - 12.7), a decreased neutrophil count (ROR, 6.1; 95% CI, 4.07 - 9.16), and lymphadenitis (ROR, 8.34; 95% CI, 4.2 - 16.6). Our results revealed the safety profile of drugs for the treatment of JIA patients. It was suggested that there is a diversity in drugs and their strength of association with adverse events in JIA patients. Our results may provide useful information for the treatment of JIA patients, although further research with more data is needed.

DOI： 10.5414/CP204255

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Molecular Sciences  

(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5–20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32–0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.

DOI： 10.3390/ijms23168859

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：(公社)日本薬学会  

日本臨床腫瘍学会では進行癌に対する医学を習得するための対面でのセミナーを毎年実施していた。しかしCOVID-19パンデミックにより、今年はウエブによるセミナーを開催せざるを得なくなった。腫瘍領域に対する初心者と中等度の技術の薬剤師に、オンラインセミナー(Web)がどのように影響したかを調べる質問票調査を行った。1756名のWeb参加者のうち1661名がWeb前に、1586名がWeb後に回答した。すべての7単元でWeb後の知識スコアの中央値は、Web前のスコアよりも有意に高かった。7単元の知識の程度に関する主成分分析では、スコア改善群は年齢が若く、薬剤師としての経験が浅く、非学会員で、過去の学会のセミナーの経験が少ないことを示していた。Webは都会や田舎の在住に関係なく、均一の学習効果を発揮した。

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Durvalumab is a human monoclonal antibody targeting programmed cell death ligand 1. It is classified as an immune checkpoint inhibitor and has shown high efficacy as maintenance therapy after chemoradiation for stage III non-small-cell lung cancer and as the primary treatment for small-cell carcinoma. Interstitial lung disease is the most common adverse event leading to durvalumab discontinuation. Hence, this study was aimed at assessing the incidence and timing of durvalumab-induced lung toxicity by using the Japanese Adverse Drug Event Report (JADER) database. PATIENTS AND METHODS: Adverse Adverse events (AEs) of durvalumab reported from August 2018 to March 2021 were extracted. Data on lung AEs were analysed to estimate relative risk using reporting odds ratios (RORs) and 95% confidence interval (CIs). Furthermore, the times of onset of signs of lung toxicity were also estimated. RESULTS: Overall, 2,162 AEs attributable to durvalumab were obtained. Of these, 1,239 were lung toxicities, the most common among which were pneumonia, interstitial lung disease, and radiation-associated pneumonitis. The corresponding RORs (95% CIs) for these signs were 271.50 (244.79-301.11), 5.96 (5.29-6.72), and 713.21 (595.04-854.85), respectively. The median (interquartile range) times of onset were 32.5 (28.5-35.5), 31.5 (28.5-41.5), and 28.5 (28.5-30.5) days, respectively. CONCLUSION: Among the AEs of durvalumab, pneumonia, interstitial lung disease, and radiation-induced pneumonitis were associated with high RORs, suggesting a strong causal relationship with durvalumab. Interstitial lung disease and radiation-induced pneumonitis most often occurred approximately 30 days after treatment initiation, suggesting that monitoring for adverse events during this period is important.

DOI： 10.21873/anticanres.15844

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To identify risk factors for opioid-induced constipation (OIC). METHODS: This study retrospectively analyzed 175 advanced cancer patients who were receiving pain treatment with opioids and were newly prescribed laxatives for OIC at Seirei Hamamatsu General Hospital between November 2016 and June 2021. For the regression analysis of factors associated with OIC, variables were extracted manually from clinical records. The effect of newly prescribed laxatives for OIC was evaluated as "effective" in cases where the number of spontaneous bowel movements increased at least once in the first 3 days. The OIC was defined based on Rome IV diagnostic criteria. Multivariate logistic regression analysis was performed to identify risk factors for OIC. Optimal cutoff thresholds were determined using receiver operating characteristic analysis. Values of P < 0.05 (two-tailed) were considered significant. RESULTS: Significant factors identified included body mass index (BMI) (odds ratio [OR] = 0.141, 95% confidence interval [CI] = 0.027-0.733; P = 0.020), chemotherapy with taxane within 1 month of evaluation of laxative effect (OR = 0.255, 95% CI = 0.068-0.958; P = 0.043), use of naldemedine (OR = 2.791, 95% CI = 1.220-6.385; P = 0.015), and addition or switching due to insufficient prior laxatives (OR = 0.339, 95% CI = 0.143-0.800; P = 0.014). CONCLUSION: High BMI, chemotherapy including a taxane within 1 month of evaluation of laxative effect, no use of naldemedine, and addition or switching due to insufficient prior laxatives were identified as risk factors for OIC in advanced cancer patients with cancer pain.

DOI： 10.1007/s00520-022-07002-9

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The anaplastic lymphoma kinase (ALK) inhibitor alectinib is recommended as a first-line treatment for ALK lung cancer. Interstitial lung disease is the most common adverse event leading to discontinuation of alectinib. The purpose of this study was to use the Japanese Adverse Drug Event Report database for the evaluation of incidence trends and timing of alectinib toxicity in the lungs. PATIENTS AND METHODS: Adverse drug reactions (ADRs) by alectinib were extracted between April 2004 and March 2021. Data related to lung toxicity ADRs were analyzed, and the relative risk was estimated using the reporting odds ratio (ROR) and 95% confidence interval (CI). The time of onset of the lung toxicity signs was noted. RESULTS: We obtained 524 reports of ADRs associated with alectinib. Of these, 157 were lung toxicity, including interstitial lung disease, lung disorder, pneumonitis, and pulmonary edema. The RORs for these signs were 10.28 (95%CI=8.38-12.60), 9.19 (5.58-15.13), 7.40 (3.67-14.88), and 7.01 (3.13-15.69), respectively. The median onset times (quartiles, 25-75%) of interstitial lung disease, lung disorder, pneumonitis, and pulmonary edema associated with alectinib treatment were 92 (36-195), 57 (51-129), 228 (62-431), and 83 (22-96) days, respectively. CONCLUSION: Among the lung toxicity signs, interstitial lung disease had the highest ROR, suggesting a strong causal relationship with alectinib treatment. Interstitial lung disease most frequently developed within 60 days after the start of treatment. These results will be useful for monitoring adverse events associated with the use of alectinib.

DOI： 10.21873/anticanres.15799

PubMed

記述言語：英語  

BACKGROUND: Ixazomib is an orally available proteasome inhibitor for multiple myeloma with adverse effects such as gastrointestinal symptoms, skin rashes, and thrombocytopenia reported in clinical trials and post-marketing surveillance, resulting in treatment discontinuation. However, comprehensive adverse event (AE) assessments for ixazomib are lacking. OBJECTIVES: Herein, we aimed to determine the frequency and risk of AEs associated with ixazomib in Japanese patients using the Japanese Adverse Event Reporting Database (JADER). Additionally, the time to onset and post hoc outcomes of unique AEs were clarified. METHODS: To investigate the association between ixazomib and AEs, we analyzed the JADER database, comprising voluntary AE reports submitted to the Pharmaceuticals and Medical Devices Agency, between April 2004 and June 2021. AEs with > 10 reports were included in the analysis, and criteria for the presence of AE signals were defined as meeting the requirements of proportional report ratio (PRR) ≥ 2 and χ2 ≥ 4. Characteristic AEs were analyzed considering time to onset and onset outcomes. RESULTS: Of 34 extracted AEs, 18 presented AE signals. The 12 post hoc outcomes with fatality rates ˃10% included septic shock (50.0%), infection (41.2%), heart failure (16.7%), pneumonia (14.2%), and tumor necrosis syndrome (13.3%). A histogram of the time to onset showed that 11 of the 18 AEs occurred from ixazomib initiation to approximately 1 month later. CONCLUSION: Our results suggest that ixazomib may increase the incidence of 18 AEs, 11 of which occurred within the first month of treatment. Furthermore, 8 AEs were found to have potentially fatal outcomes at a rate > 10%. Therefore, monitoring AEs during the first month of treatment appears necessary.  Conclusion: Our results suggest that ixazomib may increase the incidence of 18 AEs, 11 of which occurred within the first month of treatment. Furthermore, 8 AEs were found to have potentially fatal outcomes at a rate > 10%. Therefore, monitoring AEs during the first month of treatment appears necessary. .

DOI： 10.1159/000524806

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：In Vivo  

Background/Aim: High-dose chemotherapy is frequently administered to patients with hematologic malignancies, thereby causing severe adverse drug reactions (ADRs) at a relatively high frequency. To precisely monitor ADRs, we developed a medication instruction sheet (MIS) for patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination therapy for non-Hodgkin’s lymphoma (NHL). Herein, we evaluated the usefulness of the MIS for managing ADRs in patients who received R-CHOP therapy. Patients and Methods: We included patients aged ≥20 years who received R-CHOP therapy as first-line treatment for NHL at the Department of Hematology, Kyushu University Hospital, between August 2014 and December 2018. Medical professionals evaluated the possible occurrence of ADRs according to the present MIS and ADRs were graded according to the Common Toxicity Criteria, version 4.0 (National Cancer Institute, Bethesda, MD, USA). Finally, the accuracy of the MIS in predicting the occurrence of ADRs of different grades and during definite periods was evaluated. Results: Seventy-five patients with NHL were included in the present study. Overall, 359 ADR events were monitored, which were predicted ADR items listed in the MIS. Among these, 254 (71%) events occurred during the same period as those listed in the MIS. The onset timing of any grade of an infusion reaction and peripheral neuropathy precisely matched those listed in the MIS. However, the accuracy of the MIS was reduced in patients with thrombocytopenia (42%). Conclusion: The present MIS could be useful for monitoring ADRs in patients with cancer undergoing R-CHOP therapy.

DOI： 10.21873/invivo.12852

Web of Science

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Anticancer Research  

Background/Aim: Bendamustine-associated skin damage occurs frequently in Japan and can have a profound impact on health-related quality of life. To our knowledge, there are no reports on the timing of skin damage caused by bendamustine. This study assessed trends in and the time to onset of skin damage caused by bendamustine using the Japanese Adverse Drug Reaction Reporting Database (JADER). Patients and Methods: Data related to skin damage with more than five reported cases from April 2004 to March 2021 were extracted from JADER, and the relative risk of adverse events was estimated using the reporting odds ratio and 95% confidence interval. The data were analyzed for time to onset of skin damage. Results: JADER included a total of 2,450 reports of adverse drug reactions from bendamustine. Of these, 170 skin ailments of 10 types were reported to be associated with bendamustine. Significant associations for skin damage were found for rash, herpes zoster, and infusion-related reactions. The reporting odds ratios (with 95% confidence interval) for rash, herpes zoster, and infusion-related reaction were 1.63 (1.19-2.21), 3.25 (2.20-4.78), and 7.25 (4.84-10.85), respectively. The median onset (interquartile range) of rash, herpes zoster, and infusion-related reactions caused by bendamustine were 13 (10-28), 60 (28-107), and 6 (1-28) days, respectively. Conclusion: A comprehensive study using a pharmacovigilance approach enabled us to identify that a rash or infusion-related reaction may be expected within 2 weeks of treatment with bendamustine and that the onset of herpes zoster occurs at a median of 2 months after treatment with bendamustine.

DOI： 10.21873/anticanres.15752

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：(一社)日本臨床腫瘍薬学会  

記述言語：日本語   出版者・発行元：(一社)日本臨床腫瘍薬学会  

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The status of community pharmacists' involvement in inappropriate prescription practices among outpatients who visit community pharmacies has not been reported in Japan. Therefore, this study described community pharmacists' interventions aimed at the discontinuation of inappropriate drugs or the reduction of drug doses. METHODS: We conducted a multicentre prospective observational study of pharmacists' interventions on inappropriate prescriptions for outpatients during a 1-month period in September 2018. A total of 28 pharmacists from 28 community pharmacies in Japan participated in this study. We analysed cases in which pharmacists discontinued drugs or changed the doses due to drugs being inappropriate, adverse effects, duplication of pharmacological effects and drug-drug interactions. KEY FINDINGS: Community pharmacists provided interventions for 736 patients at an average of 26.2 patients per day during the study period. The pharmacists recommended that doctors discontinue inappropriate drugs or reduce the doses of regular drugs for 103 patients (13.9%). Among the 107 pharmacist recommendations to decrease inappropriate prescriptions, 83 (77.6%) were accepted, including 62 cases of discontinuation (57.9%) and 21 of drug dose reduction (19.6%). A total of 122 drugs were discontinued according to pharmacists' recommendations. In addition, pharmacists' intervention improved sleepiness, sedation and cognitive function. CONCLUSIONS: This study shows the active involvement of community pharmacists in polypharmacy by discontinuing inappropriate drugs or reducing the dose of regular drugs, which may contribute to the improvement of adverse effects among outpatients.

DOI： 10.1093/ijpp/riac032

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Anticancer Research  

Background/Aim: The occurrence of chemotherapy-related serious adverse events (AEs) is associated with a poor prognosis of hematopoietic malignancies. We have developed a medication guidance sheet (MGS) for monitoring AEs occurring when combining chemotherapy with etoposide, methylprednisolone, cisplatin, cytarabine, and rituximab (ESHAP±R). In this study, the usefulness of MGS was investigated in non-Hodgkin’s lymphoma patients. Patients and Methods: The MGS was used to monitor AEs in 48 adult patients receiving ESHAP±R. The prediction accuracy of the MGS was estimated before and after modification based on practical data. Results: A total of 246 AEs developed, all of which were predicted by the MGS. Among them, 149 events (61%) occurred during the same period as those predicted by the MGS. After modification of MGS for the onset and duration of AEs, the accuracy increased to 84%. Conclusion: The accuracy of the original MGS for ESHAP±R was insufficient but greatly improved after the AEs duration modification.

DOI： 10.21873/anticanres.15686

Web of Science

Scopus

PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

WHAT IS KNOWN AND OBJECTIVES: As for adverse events (AEs) caused by everolimus, findings from clinical trials and post-marketing surveillance have reported interstitial lung disease, hyperglycaemia, cardiovascular disease, etc. However, these reports are limited to incidence, and detailed studies on the risk of occurrence, time to onset and post-event clinical outcomes are only related to hyperglycaemia. The purpose of this study was to perform a comprehensive analysis of adverse events during everolimus therapy in patients with renal cell carcinoma (RCC) using the Japanese Adverse Event Report database. METHODS: Data reported between April 2004 and June 2021 in the Japanese Adverse Drug Event Report database were extracted for use. The reported odds ratio, time to onset and post-event course were analysed for the top 30 adverse events reported. RESULTS AND DISCUSSION: Among the top 30 adverse events, 23 adverse event signals were detected and classified into seven categories: lung-related AEs, haematological-related AEs, cancer progression, blood glucose-related AEs, hepatic-related AEs, renal-related AEs and others. The lung-related adverse events category was the most common, and the proportion of fatal outcomes after the occurrence of two adverse events related to infectious pneumonia was more than 10%. WHAT IS NEW AND CONCLUSION: A comprehensive survey of adverse events associated with everolimus administration using the pharmacovigilance database revealed that pulmonary and haematological AEs are frequently reported. The results suggest that attention should be paid to the occurrence of lung disorders because they may lead to fatal outcomes.

DOI： 10.1111/jcpt.13648

PubMed

記述言語：日本語   出版者・発行元：大阪医科薬科大学薬学部  

無菌調製実技セミナーの受講者を対象に、受講前、セミナー第1部受講後(座学講義および基礎実技)、第2部受講後(応用実技等)に質問紙調査を実施し、セミナーの有用性について評価、検討した。受講者は11名(勤務年数10年以上7名、5年以上10年未満2名、1年から5年未満1名、無回答1名)であり、調査用紙は全員から回収された。セミナーの満足度は無菌調製に必要な基本的な知識や基礎実技に対しての満足度は、「満足」5名、「やや満足」2名であった。クリーンベンチを使用した無菌操作を伴った実技での満足度は「満足」8名、「やや満足」との回答はなかった。セミナーの難易度は第1部、第2部ともに「難しい」と回答した受講者が半数以上となった。セミナーの活用度については「非常に役に立つ」7名、「役に立つ」4名との回答で、「役に立たない」との回答はなかった。実施したセミナーの意義は高く、有用であったと考えられた。

記述言語：日本語   出版者・発行元：大阪医科薬科大学薬学部  

無菌調製実技セミナーの受講者を対象に、受講前、セミナー第1部受講後(座学講義および基礎実技)、第2部受講後(応用実技等)に質問紙調査を実施し、セミナーの有用性について評価、検討した。受講者は11名(勤務年数10年以上7名、5年以上10年未満2名、1年から5年未満1名、無回答1名)であり、調査用紙は全員から回収された。セミナーの満足度は無菌調製に必要な基本的な知識や基礎実技に対しての満足度は、「満足」5名、「やや満足」2名であった。クリーンベンチを使用した無菌操作を伴った実技での満足度は「満足」8名、「やや満足」との回答はなかった。セミナーの難易度は第1部、第2部ともに「難しい」と回答した受講者が半数以上となった。セミナーの活用度については「非常に役に立つ」7名、「役に立つ」4名との回答で、「役に立たない」との回答はなかった。実施したセミナーの意義は高く、有用であったと考えられた。

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

It is essential for oncology pharmacists to update their knowledge, skills, and ethical attitudes. The Japanese Society of Pharmaceutical Oncology is an academic society for healthcare professionals involved in cancer treatment. It has conducted in-person seminars every year to cultivate the knowledge necessary for practicing advanced cancer medicine. Owing to the coronavirus disease (COVID-19) pandemic, the society was obligated to conduct a web-based seminar this year. A questionnaire survey was conducted before and after the webinar to explain how it works and to assess the learning attitudes of beginner and moderately skilled pharmacists in the field of oncology. Questionnaire surveys were conducted with the participants before and after watching the webinar. The questionnaires sought to determine participants' perspectives on the webinar and their knowledge of the seven modules. Of the 1756 webinar attendees, 1661 (94.6%) answered the pre-webinar survey and 1586 (90.3%) answered the post-webinar survey. Results indicate that the median post-webinar knowledge score was significantly higher than the median pre-webinar score (p < 0.001) in all modules. Principal component analysis of the degree of knowledge of seven modules revealed that the improved score group consisted of those from younger age groups, with less experience as pharmacists, non-society members, and those with less experience in past society seminars. Moreover, the web-based seminar provided a uniform learning effect throughout the country without distinguishing between urban and rural learners. The web-based educational program was an acceptable educational tool for Japanese oncology pharmacists.

DOI： 10.1248/bpb.b21-00844

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Opioid-induced constipation (OIC) is one of the most common adverse events of opioid therapy and can severely reduce quality of life (QOL). Naldemedine is the orally available peripheral-acting μ-opioid receptor antagonist approved for OIC treatment. However in daily clinical practice, some cancer patients show insufficient control of OIC even while receiving naldemedine. OBJECTIVE: To identify factors associated with non-response to naldemedine in cancer patients. METHODS: This study retrospectively analyzed 127 cancer patients prescribed naldemedine at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. For the regression analysis of factors associated with OIC, variables were extracted manually from electronic medical records. Naldemedine had been prescribed by the attending physician after the presence of OIC had been defined with reference to Rome IV diagnostic criteria. Naldemedine was evaluated as "effective" in cases where the number of defecations increased at least once in the first 3 days after starting naldemedine. Multivariate logistic regression analysis was performed to identify factors associated with non-response to naldemedine. The data used were from the group of patients who received naldemedine in our previous study. RESULTS: Factors significantly associated with non-response to naldemedine included chemotherapy with taxanes within 1 month of evaluation of naldemedine effect (odds ratio [OR] = 0.063; 95% confidence interval [CI] = 0.007-0.568), and addition of or switching to naldemedine due to insufficient efficacy of prior laxatives (OR = 0.352, 95% CI = 0.129-0.966). CONCLUSION: The identification of factors associated with non-response to naldemedine prescribed for OIC may help improve QOL among cancer patients.

DOI： 10.1371/journal.pone.0278823

PubMed

記述言語：英語  

BACKGROUND: Carfilzomib is a proteasome inhibitor widely used for the treatment of multiple myeloma. However, cardiac adverse events (CAEs) are a serious side effect of carfilzomib administration. Observational studies based on systematic reviews and real-world data have revealed that the risk of CAEs tends to be high. However, there have been no reports on the incidence of CAEs associated with carfilzomib in Japanese patients. Furthermore, there have been no reports on the timing and post-event outcomes of CAEs. OBJECTIVES: The purpose of this study was to identify the trends in carfilzomib-associated adverse events, the time to onset of CAEs, and the clinical outcomes after the occurrence of CAEs using the Japanese Adverse Drug Event Report (JADER) database. METHOD: We analyzed data from the JADER database, which contains reports of spontaneous adverse events submitted to the Pharmaceutical and Medical Device Agency, between April 2004 and December 2020. The relative risk of adverse events was estimated using the reporting odds ratio. The time to onset and post-event outcomes were evaluated for adverse cardiotoxic events with >10 reports. RESULTS: The reporting rate was significantly higher for all 6 detected CAEs. A time-to-onset histogram of the 6 CAEs showed that they all occurred early after carfilzomib administration. The median time of onset of heart failure, congestive heart failure, and acute heart failure was approximately 2 weeks after treatment. The adverse events with the largest proportion of fatal clinical outcomes were acute heart failure (26%) and heart failure (9.5%). CONCLUSIONS: This study suggests that the early signs and symptoms of potential fatal heart failure should be monitored during carfilzomib treatment.

DOI： 10.1159/000519687

PubMed

総ページ数：xvii, 908p   記述言語：日本語  

CiNii Books

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

担当区分：筆頭著者  

記述言語：日本語   出版者・発行元：(株)薬事新報社  

担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(株)薬事新報社  

担当区分：筆頭著者  

記述言語：日本語   出版者・発行元：(株)薬事新報社  

担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(株)薬事新報社  

記述言語：日本語   出版者・発行元：大阪医科薬科大学薬学部  

無菌調製実技セミナーの受講者を対象に、受講前、セミナー第1部受講後(座学講義および基礎実技)、第2部受講後(応用実技等)に質問紙調査を実施し、セミナーの有用性について評価、検討した。受講者は11名(勤務年数10年以上7名、5年以上10年未満2名、1年から5年未満1名、無回答1名)であり、調査用紙は全員から回収された。セミナーの満足度は無菌調製に必要な基本的な知識や基礎実技に対しての満足度は、「満足」5名、「やや満足」2名であった。クリーンベンチを使用した無菌操作を伴った実技での満足度は「満足」8名、「やや満足」との回答はなかった。セミナーの難易度は第1部、第2部ともに「難しい」と回答した受講者が半数以上となった。セミナーの活用度については「非常に役に立つ」7名、「役に立つ」4名との回答で、「役に立たない」との回答はなかった。実施したセミナーの意義は高く、有用であったと考えられた。