Safety and Risk of Pharmacotherapy最新文献

{"title":"Antipsychotic-Induced QT Prolongation and Torsade de Pointes in Patients with Mental Disorders: A Review","authors":"R. Nasyrova, A. V. Kidyaeva, M. M. Petrova, N. A. Shnayder","doi":"10.30895/2312-7821-2024-410","DOIUrl":"https://doi.org/10.30895/2312-7821-2024-410","url":null,"abstract":"INTRODUCTION. The high risk of life-threatening ventricular arrhythmias, particularly Torsade de Pointes (TdP), makes QT prolongation one of the most significant adverse drug reactions (ADRs) due to cardiotoxicity associated with antipsychotics (APs). AIM. This study aimed to systematise information on the effects of APs on QT interval duration and TdP risk in patients with mental disorders and to provide recommendations on preventive measures for practising psychiatrists and clinical pharmacologists.DISCUSSION. The authors searched information in PubMed, eLIBRARY.RU, and Google Scholar. The analysis included full-text articles on the results of placebo-controlled studies, crossover studies, case–control studies, systematic reviews, meta-analyses, and Cochrane reviews published from 1 September 2013 to 30 September 2023. The main mechanism of AP cardiotoxicity is the inhibition of voltage-gated ion channels (primarily potassium channels) in the cardiomyocyte membrane. Most first-generation APs are associated with dose-dependent QTc prolongation; thioridazine, chlorpromazine, and levomepromazine pose the highest risk of QTc prolongation and TdP. The results of this review do not support the hypothesis of a lower risk of QTc prolongation with next-generation APs than with first-generation APs. The correlation between serum AP levels and QTc prolongation severity is less characteristic of second- and third-generation APs. However, all second-generation APs lengthen the QTc interval and increase the risk of TdP, with clozapine and olanzapine posing the highest risk. Depending on the risk of QTc prolongation, APs can be divided into 3 groups: low-risk products (aripiprazole, lurasidone, cariprazine, paliperidone, and zuclopentixol), moderate-risk products (quetiapine, perphenazine, fluphenazine, olanzapine, clothiapine, and haloperidol), and high-risk products (chlorpromazine, promazine, clozapine, levomepromazine, and ziprasidone). The relationship between AP-induced QTс prolongation and TdP is ambiguous. If an AP exerts a homogeneous effect on cardiomyocytes, the risk of TdP remains low despite significant QTс prolongation.CONCLUSIONS. The summarised data on AP effects on QT interval duration and TdP risk in patients with mental disorders as well as the proposed recommendations for reducing TdP risk may be in demand by psychiatrists and clinical pharmacologists selecting AP and may help minimise the likelihood of potentially fatal AP-induced arrhythmogenic cardiac ADRs.","PeriodicalId":510845,"journal":{"name":"Safety and Risk of Pharmacotherapy","volume":" 875","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141127636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the Consumption of Medicinal Products Associated with a High Risk of Drug-Induced Liver Injury in Patients with COVID-19","authors":"V. I. Petrov, A. Ryazanova, N. S. Tokareva","doi":"10.30895/2312-7821-2024-396","DOIUrl":"https://doi.org/10.30895/2312-7821-2024-396","url":null,"abstract":"INTRODUCTION. The risk of liver damage correlates with the severity of COVID-19. However, a growing number of studies have shown an association between liver function impairment and combinations of medicinal products used to treat COVID-19.AIM. The study aimed to analyse the annual consumption of medicinal products associated with a high risk of drug-induced liver injury (DILI) used as part of combination therapy in COVID-19 patients and to review a number of medication administration records in order to develop measures to prevent DILI.MATERIALS AND METHODS. The study used the ATC/DDD methodology to study consumption data for 2020, 2021, and 2022 and analysed a sample of 1250 inpatient medical records and medication administration records of COVID-19 patients treated in a Volgograd region hospital converted into a COVID-19 care centre. For genetically engineered biologicals and cyclophosphamide, which were lacking DDDs, the authors calculated the volume of consumption using the average dose per treatment course. The authors identified medicines capable of causing clinically apparent liver damage (according to the LiverTox database and Russian clinical practice guidelines) and/or elevated liver enzymes in ≥1% of patients (according to safety reports).RESULTS. The study found that 28% of the medicinal products used in combination for inpatient treatment of COVID-19 were associated with a high risk of DILI. In 2020, 2021, and 2022, the total consumption of medicinal products associated with a high risk of DILI was 342.3, 425.3, and 402.3 DDDs per 100 bed days, and the total consumption of genetically engineered biologicals (administered as a single dose) and cyclophosphamide was 3.5, 16.9, and 29.7 average course doses per 100 patients, respectively. According to the selective analysis of medical records, 19.8% (247/1250) reported concomitant use of 5 or more medicinal products associated with a high risk of DILI, which increased the risk of adverse drug interactions leading to DILI. In 2022, the most prescribed medicinal products with a high risk of DILI were omeprazole (188.7 DDDs per 100 bed days), non-steroidal anti-inflammatory drugs and paracetamol (54.4 DDDs per 100 bed days), atorvastatin (46.2 DDDs per 100 bed days), levofloxacin (26.4 DDDs per 100 bed days), ceftriaxone (20.5 DDDs per 100 bed days), favipiravir (17.3 DDDs per 100 bed days), and genetically engineered biologicals (24.0 DDDs per 100 bed days).CONCLUSIONS. To reduce the risk of DILI in COVID-19 patients admitted to infectious disease units, including the risk of DILI due to drug interactions, it is necessary to limit the use of hepatotoxic antibacterial agents, proton-pump inhibitors, and non-steroidal anti-inflammatory drugs, or consider alternative medicinal products with a lower risk of hepatotoxicity.","PeriodicalId":510845,"journal":{"name":"Safety and Risk of Pharmacotherapy","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Signal Detection for COVID-19 Medicinal Products Based on Retrospective Analysis of Spontaneous Reports from the Russian Pharmacovigilance Database","authors":"S. Mishinova, A. Kolbin, Y. Polushin, E. V. Verbickaya","doi":"10.30895/2312-7821-2023-382","DOIUrl":"https://doi.org/10.30895/2312-7821-2023-382","url":null,"abstract":"SCIENTIFIC RELEVANCE. The pandemic of novel coronavirus infection (COVID-19) led to a drastic increase in the use of medicinal products of various therapeutic groups and increased spontaneous reporting of adverse drug reactions (ADRs). Therefore, it is necessary to analyse the reported information to identify potential safety signals.AIM.  This study aimed at systematisation and quantitative analysis of data on the safety of COVID-19 medicinal products from the Russian pharmacovigilance database.MATERIALS AND METHODS. This retrospective analysis included spontaneous ADR reports submitted to the Russian pharmacovigilance database from 1 January 2020 to 31 December 2022. The authors applied disproportionality analysis to generate safety signals.RESULTS. During the stated period, the database website published 873 spontaneous reports on 1,636 ADRs associated with COVID-19 treatment. Most ADRs were associated with favipiravir (493 reports), hydroxychloroquine (87 reports), and olokizumab (85 reports). The most common ADRs included 273 (16.7%) abnormal investigation results, 203 (12.4%) hepatobiliary disorders, and 191 (11.6%) gastrointestinal disorders. The majority of adverse events, 674 (77%) cases, had favourable outcomes. Using frequency-based disproportionality analysis, the authors identified 23 potential safety signals based on disproportionately reported ADRs for azithromycin, dexamethasone, levilimab, lopinavir+ritonavir, molnupiravir, olokizumab, tofacitinib, tocilizumab, umifenovir, and favipiravir.CONCLUSIONS. The new safety signals require additional assessment of ADR reporting forms for causal relationship analysis, validation, prioritisation, and clinical interpretation. The frequency-based method did not identify safety signals for hydroxychloroquine, remdesivir, baricitinib, sarilumab, and anti-COVID-19 human immunoglobulin, but this does not rule out the possibility of detecting new causal relationships.","PeriodicalId":510845,"journal":{"name":"Safety and Risk of Pharmacotherapy","volume":"224 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139822715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Signal Detection for COVID-19 Medicinal Products Based on Retrospective Analysis of Spontaneous Reports from the Russian Pharmacovigilance Database","authors":"S. Mishinova, A. Kolbin, Y. Polushin, E. V. Verbickaya","doi":"10.30895/2312-7821-2023-382","DOIUrl":"https://doi.org/10.30895/2312-7821-2023-382","url":null,"abstract":"SCIENTIFIC RELEVANCE. The pandemic of novel coronavirus infection (COVID-19) led to a drastic increase in the use of medicinal products of various therapeutic groups and increased spontaneous reporting of adverse drug reactions (ADRs). Therefore, it is necessary to analyse the reported information to identify potential safety signals.AIM.  This study aimed at systematisation and quantitative analysis of data on the safety of COVID-19 medicinal products from the Russian pharmacovigilance database.MATERIALS AND METHODS. This retrospective analysis included spontaneous ADR reports submitted to the Russian pharmacovigilance database from 1 January 2020 to 31 December 2022. The authors applied disproportionality analysis to generate safety signals.RESULTS. During the stated period, the database website published 873 spontaneous reports on 1,636 ADRs associated with COVID-19 treatment. Most ADRs were associated with favipiravir (493 reports), hydroxychloroquine (87 reports), and olokizumab (85 reports). The most common ADRs included 273 (16.7%) abnormal investigation results, 203 (12.4%) hepatobiliary disorders, and 191 (11.6%) gastrointestinal disorders. The majority of adverse events, 674 (77%) cases, had favourable outcomes. Using frequency-based disproportionality analysis, the authors identified 23 potential safety signals based on disproportionately reported ADRs for azithromycin, dexamethasone, levilimab, lopinavir+ritonavir, molnupiravir, olokizumab, tofacitinib, tocilizumab, umifenovir, and favipiravir.CONCLUSIONS. The new safety signals require additional assessment of ADR reporting forms for causal relationship analysis, validation, prioritisation, and clinical interpretation. The frequency-based method did not identify safety signals for hydroxychloroquine, remdesivir, baricitinib, sarilumab, and anti-COVID-19 human immunoglobulin, but this does not rule out the possibility of detecting new causal relationships.","PeriodicalId":510845,"journal":{"name":"Safety and Risk of Pharmacotherapy","volume":"19 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139882542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnesium Orotate Influence on Thoracic Aorta in Laboratory Rabbits Receiving Levofloxacin","authors":"N. V. Izmozherova, D. V. Zaytsev, V. V. Bazarny, V. Bakhtin, L. Polushina, M. Kopenkin, D. V. Tolstykh, E. Mukhlynina","doi":"10.30895/2312-7821-2024-393","DOIUrl":"https://doi.org/10.30895/2312-7821-2024-393","url":null,"abstract":"Scientific relevance. Fluoroquinolones are antibacterial agents associated with adverse drug reactions (ARDs), including aortic lesions; this ARD risk limits the use of fluoroquinolones. Moreover, fluoroquinolones have been reported to induce lesions in other connective tissues (cartilage, tendons), associated with magnesium deficiency.Aim. The study aimed to analyse the effects of magnesium orotate on the thoracic aorta in laboratory rabbits treated with levofloxacin.Materials and methods. The study randomised laboratory rabbits into 3 groups of 10 animals each to receive oral doses of either the carrier solution (control group), or 150 mg/kg/day levofloxacin (levofloxacin group), or 150 mg/ kg/day levofloxacin and 140 mg/kg/day magnesium orotate (levofloxacin/magnesium group). After 14 days of treatment, venous blood samples were taken to determine the serum levels of magnesium, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), as well as MMP-9 to TIMP-1 ratios. The authors conducted morphological and mechanical characterisation of thoracic aorta samples; the mechanical characterisation involved uniaxial tensile testing. Data are presented as the mean and standard deviation values.Results. The study did not detect any changes in the serum MMP-9, TIMP-1, and magnesium levels or in the MMP-9/TIMP-1 ratios. The authors identified foci of moderate elastic fibre fragmentation in the aortic media in 5 of 10 aortic samples from the levofloxacin group, in 1 of 10 samples from the levofloxacin/magnesium group, and in none from the control group (p=0.013). Rabbits from the levofloxacin group had significantly fewer medial elastic membranes than the others (p=0.015; vs the control group: p=0.022), and their elastic membranes were thinner by an average of 1.4 μm (16%) (p=0.010, vs the control group: p=0.022, vs the levofloxacin/ magnesium group: p=0.019). The analysis of covariance confirmed the dissimilarity of the relationships between the strength of the aortic wall and the quantity of medial elastic membranes in the three study groups.Conclusions. After 14 days of treatment, levofloxacin at a dose of 150 mg/kg/day reduced the elastin content in the tunica media as well as the thickness and strength of the membrane and promoted membrane fragmentation. These changes were accompanied by a decrease in vessel strength. The addition of magnesium orotate at a dose of 140 mg/kg/day preserved the structure of the medial elastic elements and prevented the loss of the aortic wall tensile strength. The results confirm the role of magnesium deficiency in the development of fluoroquinolone-induced aortic injury.","PeriodicalId":510845,"journal":{"name":"Safety and Risk of Pharmacotherapy","volume":"95 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139605976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}