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Amphotericin B deoxycholate (AMPH-B) is a polyene macrolide with antifungal activity. Liposomal AMPH-B (L-AMB) was developed to reduce side effects while maintaining antifungal activity. This study was aimed at evaluating and comparing the adverse event profiles of AMPH-B and L-AMB using a spontaneous reporting system. We analyzed the adverse event reports of AMPH-B and L-AMB from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Case report counts of adverse events were generated according to the preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA). Standardized MedDRA queries (SMQs) and system organ classes (SOCs) were used to compare the organ-specific adverse event profiles of AMPH-B and L-AMB. The reporting odds ratio and proportional reporting rate were used to detect pharmacovigilance signals. The FAERS database contains 21,173,818 cases from January 2004 to March 2024. Adverse events were reported in 2438 cases receiving AMPH-B treatment and 3344 cases receiving L-AMB treatment, including 848 and 1591 cases receiving intravenous AMPH-B and L-AMB injections, respectively. The most frequently reported drug-related adverse event in the AMPH-B and L-AMB groups was hypokalemia. SOCs with statistically significant differences were "Inv" (laboratory tests), "Resp" (respiratory, thoracic, and mediastinal disorders), "Genrl" (general and systemic disorders and conditions at the site of administration), "Card" (cardiac disorders), and "Blood" (blood and lymphatic system disorders). No statistically significant difference was observed in the SMQ profile of adverse events in "Renal" (renal and urinary disorders) and "Hepat" (hepatobiliary disorders) between the L-AMB and AMPH-B formulations in this study. Based on real-world data from FAERS, adverse event profiles of AMPH-B and L-AMB were compared. No statistically significant difference was observed in the SMQ profile of adverse events in the renal and hepatic SOCs between the L-AMB and AMPH-B formulations. Our results suggest that L-AMB is more tolerated by the kidneys than AMPH-B., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The authors disclose the receipt of the following financial support for the research, authorship, and/or publication of this article. This research was partially supported by JSPS KAKENHI,Grant Numbers 23H05264, 21K11100, and 21K06646. The funders played no role in the study design, data collection and analysis, decision to publish this article, or article preparation. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nokura et al.)

Introduction In neuropsychiatric pharmacotherapy, neuroleptic malignant syndrome (NMS) is a potentially serious side effect of antipsychotics characterized primarily by fever, disorientation, extrapyramidal disorders, and autonomic nervous system imbalance, which can lead to death if left untreated. We visualized the NMS profile of antipsychotics using a self-organizing map (SOM). We combined it with decision tree analysis to discriminate between 31 antipsychotics in more detail than typical antipsychotic (TAP) and atypical antipsychotic (AAP) classifications. Method A total of 20 TAPs and 11 AAPs were analyzed. We analyzed NMS reports extracted from the Japanese Adverse Drug Event Report (JADER) database based on standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (Standardized MedDRA Queries (SMQ) code: 20000044, including 68 preferred terms). The SOM was applied using the SOM package in R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results The Japanese Adverse Drug Event Report (JADER) database contained 887,704 reports published between April 2004 and March 2024. The numbers of cases of NMS (SMQ code: 20000044) reported for risperidone, aripiprazole, haloperidol, olanzapine, and quetiapine were 1691, 1294, 1132, 1056, and 986, respectively. After the antipsychotics were classified into six units using SOM, they were adapted for decision tree analysis. First, 31 antipsychotics branched off into groups with loss of consciousness, with one group (10 TAPs) consisting entirely of TAPs, and the other consisting of antipsychotics that were further separated into two groups with coma induced by TAPs and AAPs. Conclusion The results of this study provide a reference for healthcare providers when predicting the NMS characteristics induced by each drug in patients, thereby facilitating the effective treatment of schizophrenia., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was partially supported by JSPS KAKENHI Grant Number, 21K06646 and 21K11100. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Miyasaka et al.)

Background: Acute generalized eruptive pustulosis (AGEP) is a rare, but serious, drug-related adverse event. This study aimed to determine the relationships between AGEP and age, sex, primary disease, and prescription medications using a database of adverse drug events, namely, the Japanese Adverse Drug Event Report (JADER) database., Methods: In this retrospective observational study, we analyzed AGEP reports extracted from the JADER database based on the preferred term for AGEP (code 10048799). We evaluated the effects of causative drugs, underlying diseases, age, and sex. The association between AGEP and prescription drugs was analyzed using the reporting odds ratio and adjusted for covariates using multiple logistic regression. Association rule mining was performed to evaluate the correlation between each combination of factors and AGEP., Results: Between April 2004 and March 2023, 823,662 reports, including 869 reports on AGEP, were entered in the JADER database. The highest percentage of reports in each age group was in males aged <10 years, and clarithromycin was the most used drug in males aged <10 years. Nasopharyngitis was the most common reason for use, and Kawasaki disease was reported as a reason for use among males under 10 years of age, but not among females., Conclusions: In boys aged <10 years, attention should be paid to the occurrence of AGEP when prescribing clarithromycin and treating Kawasaki disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mitsuhiro Nakamura reports financial support was provided by 10.13039/501100001691Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In this study, information on injectable anticancer drug use and additional fee for enhanced collaboration (AEC) and additional fee for specific drug management guidance 2 (ASD2) claims from the NDB Open Data Japan (NODJ) dataset and the number of patients with cancer according to sex and age from the National Cancer Registry (NCR) dataset were integrated and evaluated to determine the current status and challenges in pharmacist interventions for patients receiving cancer treatment. The NODJ data, including receipt data billed from 2020 to 2021, were obtained from the Ministry of Health, Labour and Welfare website. The use of injectable anticancer drugs decreased relative to the number of cancer patients aged ≥ 75 years compared to those aged < 75 years. Regarding injectable anticancer drug use, the number of AEC claims was similar between men and women, but the number of ASD2 claims was lower in men than in women. The number of times community pharmacists claimed their ASD2 was approximately 5% of the number of times hospital pharmacists claimed their AEC. This study revealed that several patients did not receive sufficient guidance from community pharmacists compared to hospital pharmacists, suggesting a potential insufficiency in the collaboration between the two groups., Competing Interests: MI is an employee of Kifune Pharmacy. The other authors declare no conflicts of interest., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Adverse events (AEs) of antipsychotic drugs include neuroleptic malignant syndrome (NMS), which presents complex clinical symptoms, resulting in a fatal outcome. In this study, the association between antipsychotic drugs and NMS was comprehensively evaluated by cluster and association analyses using the Japanese Adverse Drug Event Report (JADER) database. The analyses were performed using 20 typical antipsychotics (TAPs) alongside 9 atypical antipsychotics (AAPs). The Standardised MedDRA Queries (SMQ) database was used to analyze NMS (SMQ code: 20000044). Reporting odds ratios (RORs) were used for AE signal detection. The relationship between antipsychotic drugs and AEs for NMS was investigated by performing hierarchical cluster analysis using Ward's method. Between April 2004 and September 2021, the total number of JADER reports was 705,294. RORs (95 % confidence interval) of NMS for haloperidol, chlorpromazine, risperidone, and aripiprazole were 12.1 (11.1-13.3), 6.3 (5.7-7.0), 6.2 (5.8-6.6), and 4.7 (4.4-5.1), respectively. Three clusters were formed, with characteristics as follows: Cluster 1 consisted of only TAPs, such as bromperidol and fluphenazine, whilst having a high reporting rate of hypotension, tachycardia, dyskinesia, and dystonia. Cluster 2 consisted of all AAPs alongside several TAPs, such as haloperidol and chlorpromazine, with higher reporting rates of disturbance of consciousness, extrapyramidal disorders (excluding dyskinesia and dystonia), and serotonin syndrome. Cluster 3 consisted of only perphenazine, whilst having a higher reporting rate of coma, leukocytosis, and Parkinsonism. The results of this study may therefore aid in the management of NMS using antipsychotic drugs., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mitsuhiro Nakamura reports financial support was provided by Japan Society for the Promotion of Science., (© 2023 The Authors.)

Interest in the marine cyanobacteria natural products aplysiatoxin (ATX) and oscillatoxin (OTX) has been renewed recently due to the discovery of many new analogues, some exhibiting intriguing biological activities. We sought to develop a collective synthesis of these natural products, hypothesizing that ATX could serve as a common biosynthetic precursor. Herein, we reveal that the core structure of ATX has unique multiple reactivities giving access to the distinct ring structures of five of the analogues, depending upon the specific conditions used. Based on these findings, syntheses of the O -Me derivative of five analogues neo-deBr-ATX-B, OTX-H, OTX-D, neo-deBr-ATX-H, and OTX-I were achieved from the main fragment of ATX as a common intermediate in a few steps. These synthetic studies also led us to revise the relative configuration in the elucidated structures of neo-deBr-ATX-B and OTX-H, and obtain unnatural 8- and 12-membered lactones from the same intermediate.

Oscillatoxins (OTXs) and aplysiatoxins are biosynthetically related polyketides produced by marine cyanobacteria. We previously developed a synthetic route to phenolic O-methyl analogs of OTX-D and 30-methyl-OTX-D during collective synthesis of these natural products. According to our synthetic strategy, we achieved total synthesis of OTX-D, 30-methyl-OTX-D, OTX-E, and OTX-F by deprotecting the O-methyl group in an earlier intermediate, and determined their biological activities. Although OTX-D and 30-methyl-OTX-D have been reported to show antileukemic activity against L1210 cell line, we found that their cytotoxicity in vitro against this cell line is relatively weak (IC50: 29-52 µm). In contrast, OTX-F demonstrated cell line-selective antiproliferative activity against DMS-114 lung cancer cells, which implies that OTXs target as yet unknown target molecules as part of this unique activity., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

O-Methyloscillatoxin D and its analogues were concisely synthesized by a bioinspired intramolecular Mukaiyama aldol reaction as a key step, which involves the construction of a novel spiro-ether moiety.