Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. In this way, the objective is analyzing the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients' records, in which the patient's profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (± 5.4) different medicines after the transplantation, and 7.4 (± 4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs' effects were related to, mainly, increase their immunosuppressant activity. Conclusion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs' effects to prevent and minimize side effects in transplanted recipients.

Potential medication incompatibilities in pediatric oncology prescriptions

Introduction: Pediatric oncology patients have a limited number of venous access routes and need a large number of drugs during hospitalization. This study evaluates potential medication incompatibilities (MI) in pediatric oncology prescriptions and identifies possible factors associated with the risk of their occurrence. Methods: This cross-sectional study evaluated prescriptions from a tertiary universitary hospital from December 2014 to December 2015. The association between variables and the risk of potential incompatibilities between drugs was determined by Student's t-test and Pearson's chi-square, considering p < 0.05 significant. The odds ratio was calculated considering a 95% confidence interval for each drug. Results: 385 prescriptions were evaluated. The mean age of 124 patients was 9.22 years old (SD = ± 5.10), and 50.65% were male. The most frequent diagnosis and reason for hospitalization were leukemia (27.30%) and chemotherapy (36.10%). The totally implantable catheter was the most commonly used venous access (61.30%). In 87.5% of prescriptions, there was the possibility of MI, and 2108 incompatibilities were found, considering 300 different combinations between two drugs. Age, diagnosis, reason for hospitalization, and type of venous access were risk factors for potential incompatibilities (p < 0.05). The following drugs present higher risk of potential incompatibilities: leucovorin, sodium bicarbonate, cefepime, diphenhydramine, dimenhydrinate, hydrocortisone, and ondansetron, with a significant odds ratio. Conclusion: The possibility of MI in prescriptions for pediatric oncology patients is frequent. Thus, the identification of risk factors may contribute to patient safety and to the rational use of drugs.

Which Is Safer, Chinese Medicine or Western Medicine? Comparative Analysis Based on Chinese Spontaneous Reporting Database / 中国结合医学杂志

OBJECTIVE@#To compare the safety differences between Chinese medicine (CM) and Western medicine (WM) based on Chinese Spontaneous Reporting Database (CSRD).@*METHODS@#Reports of adverse events (AEs) caused by CM and WM in the CSRD between 2010 and 2011 were selected. The following assessment indicators were constructed: the proportion of serious AEs (PSE), the average number of AEs (ANA), and the coverage rate of AEs (CRA). Further comparisons were also conducted, including the drugs with the most reported serious AEs, the AEs with the biggest report number, and the 5 serious AEs of interest (including death, anaphylactic shock, coma, dyspnea and abnormal liver function).@*RESULTS@#The PSE, ANA and CRA of WM were 1.09, 8.23 and 2.35 times higher than those of CM, respectively. The top 10 drugs with the most serious AEs were mainly injections for CM and antibiotics for WM. The AEs with the most reports were rash, pruritus, nausea, dizziness and vomiting for both CM and WM. The proportions of CM and WM in anaphylactic shock and coma were similar. For abnormal liver function and death, the proportions of WM were 5.47 and 3.00 times higher than those of CM, respectively.@*CONCLUSION@#Based on CSRD, CM was safer than WM at the average level from the perspective of adverse drug reactions.

Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency / Vendas de "kit-COVID" e reações adversas a esses medicamentos relatadas pela Agência Nacional de Vigilância Sanitária / Ventas de medicamentos del "kit-COVID" y reacciones adversas a los medicamentos notificadas por la Agencia Nacional de Vigilancia Sanitaria

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.

Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.

Determinación de factores de riesgo a reacciones adversas a medicamentos mediante farmacovigilancia intensiva en UCI / Risk factors for adverse drug reactions in patients admitted to intensive care units

Background: Patients hospitalized in intensive care units (ICU) are at higher risk of having adverse drug reactions (ADR). Aim: To determine risk factors for ADR, through intensive pharmacological surveillance at the ICU. Patients and Methods: An observational, descriptive and prospective study was made, determining risk parameters in patients who experienced ADR. Results: Eighty-five patients were surveilled and 24 (28%) had an ADR. A total of 48 drugs responsible for at least one ADR were identified. Seventy-three percent ADR were moderate and 27% were severe. The clinical variables significantly associated with ADR were a history of allergies, a high body mass index, the reason for admission, an APACHE II score ≥ 14 points, the use of invasive mechanical ventilation and more than seven days of hospitalization. The pharmacological variables associated with ADR were polypharmacy and medication associations and combinations. Conclusions: The identified risk factors have a great impact on pharmacokinetic and pharmacodynamic parameters, and should be considered to avoid the appearance of ADR.

El consumo de medicamentos en pacientes de la tercera edad / The consumption of medicines in elderly patients

Introducción: Los adultos mayores generalmente presentan diferentes patologías, lo que implica un alto consumo de medicamentos, con lo cual, este grupo poblacional constituye uno de los que mayor cantidad de errores pueden cometer en el uso de fármacos. Objetivo: Evaluar el comportamiento del consumo de fármacos en una población perteneciente a la tercera edad. Métodos: Se realizó un estudio descriptivo de corte transversal en un consultorio médico del municipio Arroyo Naranjo de La Habana en el período entre octubre de 2018 y mayo de 2019. La población estuvo conformada por 365 pacientes geriátricos con diagnóstico de enfermedad crónica no transmisible (ECNT). Se realizó un muestreo al azar para un total de 67 pacientes seleccionados. Las variables analizadas fueron: edad, sexo, ECNT asociada y medicamentos consumidos. Los datos fueron obtenidos mediante revisión de historias clínicas y entrevistas realizadas. Se realizó un análisis porcentual para determinar prevalencia en cada variable analizada. Resultados: Los medicamentos que más destacaron en la muestra fueron los antihipertensivos e hipoglucemiantes. El consumo de medicamentos fue superior en los pacientes de 75 años en adelante y fundamentalmente en las mujeres. Los hombres, por su parte, constituyeron los más irresponsables en la adherencia al tratamiento. Conclusiones: Existió correspondencia entre los tratamientos y las patologías en la mayoría de los casos con excepción de algunos pacientes en los que la relación beneficio-riesgo del tratamiento no se cumplió totalmente. Sin embargo, de manera global, se considera que no existe un adecuado uso de los medicamentos en la muestra(AU)

Introduction: Aged adults generally have different pathologies, which implies high consumption of drugs, with which, this population group is one of those that can make the higher number of errors when using medication drugs. Objective: To evaluate the behavior of drug use in an elderly population. Methods: A descriptive cross-sectional study was carried out in a medical office in Arroyo Naranjo municipality, Havana, from October 2018 to May 2019. 365 geriatric patients made up the population they had diagnosis of chronic non-communicable disease (NCD). A random sampling was carried out for a total of 67 selected patients. The variables analyzed were age, sex, associated NCD, and medications used. The data were obtained by studying medical records and interviews. A percentage analysis was carried out to determine prevalence in each variable analyzed. Results: The drugs that stood out the most in the sample were antihypertensive and hypoglycemic drugs. The consumption of drugs was higher in patients aging 75 years and older and mainly in women. Men were the most irresponsible in adherence to treatment. Conclusions: There was correspondence between the treatments and the pathologies in most cases with the exception of some patients in whom the benefit-risk ratio of the treatment was not fully met. However, generally, it is considered that there is no adequate use of the drugs in the sample(AU)

Formulários de notificação de reações adversas a medicamento nos sistemas de farmacovigilância do Brasil e outros doze países latino-americanos: análise comparativa / Adverse drug reaction notification forms of the pharmacovigilance systems in Brazil and twelve other Latin-American countries: a comparative analysis

Resumo Avaliou-se os formulários de notificação de suspeitas de reações adversas a medicamentos (RAM) do sistema de farmacovigilância do Brasil e outros doze países latino-americanos. O estudo foi composto por três etapas. Na primeira, os formulários foram pontuados em relação à presença de itens essenciais para compor uma notificação de RAM. Na segunda, as variáveis dos formulários foram quantificadas e classificadas, quanto à razoabilidade em contribuírem para a avaliação de causalidade. Na última etapa, recorreu-se à análise de agrupamento hierárquico para identificar os formulários similares. O formulário da Venezuela obteve a maior pontuação (18 pontos). A mediana das variáveis nos formulários dos países foi de 41 [26 (Guatemala) a 95 (Brasil)]. A maioria das variáveis dos formulários foram classificadas como vitais e a maior parte contribui como fator de explicação alternativo para a avaliação de causalidade. Quatro agrupamentos foram identificados (1, 2, 3 e 4). Os formulários do Brasil e da Bolívia formaram dois grupos distintos, 1 e 3 respectivamente. Há necessidade de modificação dos formulários dos países ou até mesmo exclusão de variáveis, tornando-os mais adequados ao processo de avaliação da causalidade das RAM.

Abstract The scope of this study was to assess the forms used to report suspected adverse drug reactions (ADR) to the pharmacovigilance system in Brazil and twelve other Latin-American countries. The study comprised three stages. In the first stage, the forms were attributed a score relating to the presence of critical items to generate ADR notification. In the second stage, the variables of the forms were quantified and classified regarding feasibility to contribute to an appropriate assessment of causality. In the last stage, hierarchical clustering was used to identify similar forms. The Venezuelan form achieved the highest score (18 points). The median number of variables in the forms of each country was 41 [26 (Guatemala) to 95 (Brazil)]. Most of the variables of the form were classified as life-critical and the majority contribute as an alternative explanation to causality assessment. Four clusters were identified (1, 2, 3 and 4). The forms of Brazil and Bolivia formed two distinct groups, 1 and 3 respectively. The results of this study indicate the need to change the forms of the different countries studied or even delete some variables, making them more appropriate for the process of assessment of ADR causality.

Reações adversas a medicamentos em pacientes com COVID-19 no Brasil: análise das notificações espontâneas do sistema de farmacovigilância brasileiro / Reacciones adversas a medicamentos en pacientes con COVID-19 en Brasil: análisis de las notificaciones espontáneas del sistema de farmacovigilancia brasileño / Adverse drug reactions in patients with COVID-19 in Brazil: analysis of spontaneous notifications of the Brazilian pharmacovigilance system

Em março de 2020, a Organização Mundial da Saúde anunciou a nova pandemia denominada de COVID-19, representando um desafio para os profissionais e serviços de saúde. Ainda não foi identificado um tratamento eficaz contra essa doença e vários fármacos são utilizados sem evidências de sua eficácia, que em alguns casos pode causar eventos indesejados. Esse é um estudo transversal com o objetivo de avaliar as reações adversas a medicamentos (RAMs) nos pacientes com COVID-19, identificadas entre 1º de março e 15 agosto de 2020 no Brasil, e os fatores associados ao surgimento de reações graves. Para comparar as proporções das amostras relacionadas ao notificador, paciente, fármacos e eventos adversos utilizamos os testes não paramétricos qui-quadrado e exato de Fisher, e para comparar as médias dos dados com a distribuição normal foi usado o teste t e de Mann-Whitney. Também foi realizada a análise de regressão logística multivariável, estimando as odds ratio (OR) brutas e ajustadas pelo software Stata, versão 10.0. Foram identificadas 631 RAMs em 402 pacientes. Os medicamentos mais envolvidos foram hidroxicloroquina (59,5%), azitromicina (9,8%) e a cloroquina (5,2%). As reações se manifestaram prioritariamente no sistema cardíaco (38,8%), gastrointestinal (14,4%), tecido cutâneo (12,2%) e hepático (8,9%). A cloroquina (OR = 5,4; IC95%: 1,9-15,6) e a hidroxicloroquina (OR = 2,1; IC95%: 1,2-3,6) foram os únicos medicamentos associados a RAM grave. Nossos achados fornecem subsídios para melhores práticas em farmacovigilância, contribuindo para tomadas de decisões regulatórias efetivas e seguras pela Agência Nacional de Vigilância Sanitária, para os pacientes e toda a sociedade.

En marzo de 2020 la Organización Mundial de la Salud anunció la nueva pandemia denominada COVID-19, representando un desafío para los profesionales y servicios de salud. Todavía no se identificó un tratamiento eficaz contra esta enfermedad y varios fármacos se utilizan sin evidencias de su eficacia, que, en algunos casos, pueden causar eventos indeseados. Este es un estudio transversal, con el objetivo de evaluar las reacciones adversas a medicamentos (RAMs) en pacientes con COVID-19, identificadas desde el 1º de marzo al 15 agosto de 2020 en Brasil, y los factores asociados al surgimiento de reacciones graves. Para comparar las proporciones de las muestras relacionadas con el notificador, paciente, fármacos y eventos adversos, utilizamos los tests no paramétricos chi-cuadrado y exacto de Fisher, y para comparar las medias de los datos con la distribución normal, se utilizó el test t y de Mann-Whitney. También se realizó un análisis de regresión logística multivariable, estimando las odds ratio (OR) brutas y ajustadas, mediante el software Stata, versión 10.0. Se identificaron 631 RAMs en 402 pacientes. Los medicamentos más implicados fueron: hidroxicloroquina (59,5%), azitromicina (9,8%) y la cloroquina (5,2%). Las reacciones se manifestaron prioritariamente en el sistema cardíaco (38,8%), gastrointestinal (14,4%), tejido cutáneo (12,2%) y hepático (8,9%). La cloroquina (OR = 5,4; IC95%: 1,9-15,6) e hidroxicloroquina (OR = 2,1; IC95%: 1,2-3,6) fueron los únicos medicamentos asociados a RAM grave. Nuestros resultados proporcionan apoyo para mejores prácticas en farmacovigilancia, contribuyendo a las tomas de decisiones regulatorias efectivas y seguras, por parte de la Agencia Nacional de Vigilancia Sanitaria, para los pacientes y toda la sociedad.

In March 2020, the World Health Organization announced the new COVID-19 pandemic, which represented a challenge for health services and professionals. An effective treatment against this disease has not yet been developed; as such, several drugs are used without evidence of efficacy, which in some cases may lead to unwanted events. This is a cross-sectional study with the objective of evaluating adverse drug reactions (ADRs) in patients with COVID-19, identified between March 1 and August 15, 2020, in Brazil, as well as assessing the factors associated with the emergence of severe reactions. To compare the proportions of samples related to the notifier, patient, drugs and adverse events, we used Fisher's chi-square and exact nonparametric tests; and to compare the means of the data with normal distribution, we used the Student's t-test and Mann-Whitney's test. A multivariate logistic regression analysis was also performed, estimating the crude and adjusted odds ratio (OR) by the Stata software, version 10.0. A total of 631 ADRs were identified in 402 patients. The main drugs were hydroxychloroquine (59.5%), azithromycin (9.8%) and chloroquine (5.2%). The reactions manifested primarily in the cardiac system (38.8%), gastrointestinal system (14.4%), skin tissue (12.2%) and hepatic system (8.9%). Chloroquine (OR = 5.4; 95%CI: 1.9-15.6) and hydroxychloroquine (OR = 2.1; 95CI%: 1.2-3.6) were the only drugs associated with severe ADR. Our findings provide support for better practices in pharmacovigilance, contributing to effective and secure regulatory decision-making by the Brazilian Health Regulatory Agency, patients and society as a whole.

Differential analysis of different study types in clinical safety evaluation of Xuebijing Injection / 中国中药杂志

This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.

Enlightenment of international pharmacovigilance system on establishment of pharmacovigilance system of Chinese medicine / 中国中药杂志

Pharmacovigilance system is an extension of the original adverse drug reactions monitoring and reporting system as well as an internationally recognized basic system that must be matched with the whole life cycle supervision of drugs. European Union(EU)pharmacovigilance system, World Health Orgnization(WHO) Uppsala Monitoring Center system and ICH system are internationally recognized pharmacovigilance systems. They all have their own pharmacovigilance characteristics and could provide guarantee for clinical safe drug use. With the deepening of international communication, pharmacovigilance has also been developed in China. Pharmacovigilance of Chinese medicine is a new concept based on the existing pharmacovigilance system of chemical medicine and the characteristics of Chinese medicine. In ancient China, Chinese medicine also had its own ways of early warning. Ancient medical books have records on the toxicity classification, clinical pharmacovigilance and intoxication rescue of Chinese medicine. With the increase of public recognition of Chinese medicine in recent years, especially since the government issued the 13 th Five-Year Plan for the development of Chinese medicine, the pharmaceutical industry in China has paid more and more attention to the pharmacovigilance of Chinese medicine.However, the pharmacovigilance system of Chinese medicine has not yet been established, and it still needs to be explored and improved.Therefore, it is very necessary to develop the system to standardize pharmacovigilance-related activities of Chinese medicine. In this context, this study analyzed and learned the characteristics of pharmacovigilance systems of EU, ICH, and WHO Uppsala Monitoring Center, so as to provide some enlightenment for the establishment and improvement of pharmacovigilance system of Chinese medicine.

Notificações de incidentes no espaço hospitalar: criação de um sistema de notificação interno online em hospital público federal / Incident notifications in the hospital space: creation of an online internal notification system in a federal public hospital

Introdução: O processo de notificação visa monitorar a ocorrência de incidentes para melhor compreensão e desenvolvimento de estratégias de prevenção e redução de danos, assim como promover a melhoria contínua da qualidade e segurança do cuidado prestado. O presente estudo teve como meta a estruturação de três produtos, a saber: Produto 1 ­ Produto bibliográfico técnico e tecnológico intitulado "Caracterização dos incidentes em um hospital público federal entre os anos 2014 a 2019"; Produto 2 ­ Produto bibliográfico técnico e tecnológico intitulado "Criação de sistema interno online para notificação de incidentes no espaço hospitalar: relato de experiência". Produto 3 ­ Produção técnica intitulada "Guia orientador para o preenchimento adequado dos dados no sistema interno online para notificação de incidentes". Objetivo: Criar um sistema interno online para monitoramento dos incidentes em um hospital federal, a partir do FormSUS, bem como organizar um guia orientador para a sua utilização para auxiliar os profissionais no processo de notificações. Materiais e Métodos: O primeiro produto foi um estudo transversal após pesquisa em base de dados secundários de acesso restrito referente ao período de 2014 a 2019, que identificou 10.837 incidentes classificados segundo as Metas Internacionais de Segurança do Paciente: Eventos Adversos, Incidentes sem Dano, Quase Falhas, Circunstâncias Notificáveis. O sistema de notificação foi construído por meio da plataforma do Departamento de Informática do Sistema Único de Saúde para criação de formulários públicos, conhecida como FormSUS versão 3.0. O instrumento já é existente no Ministério da Saúde com base na interface do FormSUS organizado a partir de dados, tais como: dados da internação, data da ocorrência do incidente, descrição completa do incidente, identificação do profissional notificador, contato por e-mail, telefone ou presencial, cargo e função do profissional notificador. Resultados: Finalmente, foi estruturado um guia orientador para preenchimento das notificações de forma simples, baseado em dúvidas mais frequentes, no qual se explicam detalhadamente os incidentes e a forma de acessar o sistema interno online de notificação para o envio ao Núcleo de Segurança do Paciente. Conclusões: Caracterizar e analisar os dados relacionados aos incidentes ocorridos no hospital é um exercício fundamental, pois auxilia o processo de educação contínua sobre segurança do paciente. A partir desse conhecimento, a criação de um sistema online de notificação, e do manual para o preenchimento correto dos formulários, pode contribuir para aumentar a adesão dos profissionais às notificações e trazer informações fidedignas para o desenvolvimento de estratégias que reduzam os danos ao paciente

Introduction: The notification process aims to monitor the occurrence of incidents in order to better understand and develop strategies for preventing and reducing harm, as well as promoting continuous improvement in the quality and safety of the care provided. The present study aimed at structuring three products, namely: Product 1 ­ Technical and technological bibliographic product entitled "Characterization of incidents in a federal public hospital between the years 2014 and 2019"; Product 2 ­ Technical and technological bibliographic product entitled "Creation of an internal online system for notification of incidents in the hospital space: experience report". Product 3 ­ Technical production entitled "Guiding guide for the proper filling of data in the internal online system for notification of incidents". Objective: Create an internal online system for monitoring incidents in a federal hospital, using FormSUS, as well as organizing a guiding guide for its use to assist professionals in the notification process. Materials and methods: The first product was a cross-sectional study after searching a secondary database with restricted access for the period from 2014 to 2019, which identified 10,837 incidents classified according to the International Patient Safety Goals: Adverse Events, Incidents Without Damage, Almost Failure, Circumstances Notifiable. The notification system was built using the platform of the Informatics Department of the Unified Health System to create public forms, known as FormSUS version 3.0. The instrument already exists at the Ministry of Health based on the FormSUS interface organized from data, such as: hospitalization data, date of the incident, complete description of the incident, identification of the notifying professional, contact by e-mail, telephone or in person, position and function of the notifying professional. Results: Finally, a guiding guide for filling out notifications in a simple way was structured, based on the most frequent doubts, in which the incidents are explained in detail and how to access the internal online notification system for sending to the Patient Safety Center. Conclusions: Characterizing and analyzing the data related to the incidents that occurred in the hospital is a fundamental exercise, as it helps the process of continuous education on patient safety. Based on this knowledge, the creation of an online notification system, and the manual for the correct filling of forms, can contribute to increase the professionals' adherence to the notifications and bring reliable information for the development of strategies that reduce harm to the patient

Drug-related problems in cardiac neonates under intensive care / Problemas relacionados a medicamentos em neonatos cardiopatas sob terapia intensiva

ABSTRACT Objective: To determine the frequency and nature of the Drug Related Problems (DRP) in neonates with cardiac diseases admitted to an Intensive Care Unit. Methods: This prospective cross-sectional study was developed at the Neonatal Intensive Care Unit (NICU) of a teaching maternity hospital in Brazil from January 2014 to December 2016. All neonates diagnosed with any heart disease (congenital heart disease, cardiomyopathy, arrhythmias, etc.) and who were admitted to the NICU for more than 24 hours with at least one prescribed drug were included in the study. Demographic and clinical data were collected from the records of the institution's clinical pharmacy service. DRP and their respective interventions were independently reviewed and classified by two pharmacists. DRP classification was performed through the Pharmaceutical Care Network Europe v6.2 system. Results: 122 neonates were included in the study. The frequency of neonates exposed to DRP was 76.4% (confidence interval of 95% [95%CI] 65.9-82.0), with a mean of 3.2±3.8 cases/patient. In total, 390 DRP were identified, of which 49.0% were related to "treatment effectiveness", 46.7% to "adverse reactions" and 1.0% to "treatment costs". The medicines most involved in DRP were Vancomycin (10.2%; n=46), Meropenem (8.0%; n=36) and Furosemide (7.1%; n=32). Pharmacists performed 331 interventions, of which 92.1% were accepted by physicians and nurses. Conclusions: The study showed that DRP are very frequent in patients with cardiac diseases hospitalized in the NICU, predominating problems related to the effectiveness and safety of the drug treatment.

RESUMO Objetivo: Determinar a frequência e a natureza dos problemas relacionados a medicamentos (PRMs) em neonatos cardiopatas internados em uma unidade de terapia intensiva. Métodos: Trata-se de um estudo transversal prospectivo desenvolvido na Unidade de Terapia Intensiva Neonatal (UTIN) de uma maternidade de ensino do Brasil, de janeiro de 2014 a dezembro de 2016. Todos os neonatos diagnosticados com alguma doença cardíaca (cardiopatias congênitas, cardiomiopatias, arritmias etc.) e internados na UTIN por período superior a 24 horas, com pelo menos um medicamento prescrito, foram incluídos no estudo. Dados demográficos e clínicos foram coletados a partir dos registros do serviço de farmácia clínica da instituição. Os PRMs e suas respectivas intervenções foram revisadas e classificadas independentemente por dois farmacêuticos. A classificação dos PRMs foi realizada por meio do sistema Pharmaceutical Care Network Europe versão 6.2. Resultados: Cento e vinte e dois neonatos foram incluídos no estudo. A frequência de neonatos expostos a PRM foi de 76,4% (intervalo de confiança de 95% [IC95%] 65,9-82,0), com média de 3,2±3,8 casos por paciente. Ao todo, 390 PRM foram identificados, sendo que 49,0% estiveram relacionados à "efetividade do tratamento", 46,7% a "reações adversas" e 1,0% a "custos do tratamento". Os medicamentos mais envolvidos em PRM foram: vancomicina (10,2%; n=46), meropenem (8,0%; n=36) e furosemida (7,1%; n=32). Os farmacêuticos realizaram 331 intervenções, sendo 92,1% aceitas por médicos e enfermeiros. Conclusões: O estudo mostrou que PRMs são muito frequentes em pacientes cardiopatas internados em UTIN, predominando problemas relacionados à efetividade e segurança do tratamento medicamentoso.

Characterization of adverse reactions to benznidazole in patients with Chagas disease in the Federal District, Brazil

Abstract INTRODUCTION: Benznidazole is used for treating Chagas disease (CD). This cross-sectional study aimed to characterize the adverse drug reactions (ADRs) of benznidazole at a public hospital in Brazil's Federal District. METHODS: Medical records were analyzed and ADRs were categorized by type, intensity, seriousness, and causality. RESULTS: Of the 62 patients who started benznidazole treatment for CD, 41 (66%) presented with 105 ADRs; 23 (37%) discontinued the treatment. Most reactions were classified as probable (81%), severe (63%), serious (67%), and dose-dependent (56%). CONCLUSIONS: The high incidence of ADRs because of treatment withdrawal revealed the need for safer alternatives for CD treatment.

Association of adverse drug reaction to anti-tuberculosis medication with quality of life in patients in a tertiary referral hospital

Abstract INTRODUCTION: Adverse drug reactions can develop when using anti-tuberculosis medication, and the effects of the drugs can also significantly hinder the treatment of patients. METHODS: A cross-sectional survey was conducted in 73 patients using two standardized questionnaires and the World Health Organization Quality of Life-Bref. RESULTS: All patients reported the presence of adverse drug reactions, 71.6% of which are minor and 28.3% both major and minor. The global quality of life analysis showed that patients with tuberculosis have a good average (67.3%). CONCLUSIONS: There is an association between quality of life and adverse drug reaction, educational level, and vulnerability.

COVID-19 y el sistema renina, angiotensina, aldosterona. Una relación compleja / COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship

Resumen La pandemia por COVID-19 ha tenido muy importantes repercusiones negativas, sanitarias, psicológicas, sociales y económicas para las personas, las familias, las comunidades, los países y para las para la humanidad en general. La interrelación con la edad y la presencia de enfermedades crónicas no trasmisibles (hipertensión, diabetes, obesidad, tabaquismo) parece ir mas lejos que lo que explicaría la prevalencia y distribución de ambas. Los medicamentos que actúan sobre el sistema renina-angiotensina-aldosterona, son pilares básicos en el manejo de estas enfermedades. Se sabe de tiempo atrás que estos fármacos aumentan en forma significativa la expresión en el tejido pulmonar de receptores para la enzima de conversión de angiotensina de tipo 2. Este hecho junto con el conocimiento de que la vía de entrada del virus a la célula es precisamente el receptor de ECA-2, inició una hipótesis, basada en evidencia de muy baja calidad, que rápidamente se generalizó en los medios de comunicación, de que el empleo de estos medicamentos podría ser negativo y que deberían suspenderse. La respuesta de prácticamente todas las sociedades científicas fue casi inmediata, con la indicación precisa de que no debería suspenderse el tratamiento con estos fármacos, puesto que la evidencia de su utilidad está basada en una evidencia muy sólida y de gran calidad. Casi simultáneamente también apareció la hipótesis, también basada en evidencia muy preliminar, de que estos medicamentos no solo resultan dañinos sino que son benéficos, tampoco se aceptan todavía como agentes para la prevención o tratamiento de esta enfermedad o sus complicaciones. La presente revisión relata los conocimientos actuales sobre la relación entre COVID-19 y SRAA.

Abstract The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.

Adverse drug reactions related to potential serious drug interactions in patients with cardiovascular diseases / Eventos adversos a los medicamentos relacionados con posibles interacciones medicamentosas graves en pacientes con enfermedades cardiovasculares / Eventos adversos a medicamentos relacionados às potenciais interações medicamentosas graves em pacientes com doenças cardiovasculares

ABSTRACT Objective: To assess the occurrence of adverse drug reactions associated with potential serious drug interactions identified in prescriptions of hospitalized patients with cardiovascular disease. Method: A documentary, quantitative, and cross-sectional research study. Between August and September 2016, ninety-nine prescriptions of patients hospitalized for more than 48 hours in the cardiology ward of a hospital in Rio de Janeiro were analyzed. Drug interactions were evaluated by Micromedex®, and adverse events were identified through trackers and analyzed by specialists using the Naranjo Algorithm, by means of descriptive statistics. Results: Eighteen potential serious interactions were detected in 22 drug pairs, mainly simvastatin x anlodipine (18%) and enoxaparin x clopidogrel (18%). Of the 18 medical records investigated, four trackers were found and three probable adverse events (16.6%) were defined due to hemorrhagic changes in patients. Conclusion: Drug interactions are likely to cause harm to the patient, which requires implementing barriers for the safety of the medication system.

RESUMEN Objetivo: Evaluar la manifestación de eventos adversos a los medicamentos, asociados con posibles interacciones medicamentosas graves, identificadas en las prescripciones de pacientes hospitalizados con enfermedades cardiovasculares. Método: Investigación documental, cuantitativa y transversal. Entre agosto y septiembre de 2016, se analizaron 99 prescripciones de pacientes hospitalizados durante más de 48 horas en la sala de cardiología de un hospital de Río de Janeiro. Las interacciones medicamentosas fueron evaluadas por medio de Micromedex®, y los eventos adversos fueron identificados a través de rastreadores y analizados por especialistas, con el uso del algoritmo de Naranjo y empleo de estadísticas descriptivas. Resultados: Se detectaron 18 posibles interacciones graves en 22 pares de medicamentos, principalmente entre sinvastatina x anlodipino (18%) y enoxaparina x clopidogrel (18%). Entre los 18 registros médicos investigados, se encontraron cuatro rastreadores y se definieron tres probables eventos adversos (16,6%) debido a cambios de naturaleza hemorrágica en los pacientes. Conclusión: Es probable que las interacciones medicamentosas causen daño al paciente, lo que requiere implementar barreras para la seguridad del sistema de medicación.

RESUMO Objetivo: Avaliar a ocorrência de eventos adversos a medicamentos associados às potenciais interações medicamentosas graves identificadas em prescrições de pacientes hospitalizados com doenças cardiovasculares. Método: Pesquisa documental, quantitativa, seccional. Foram analisadas entre agosto e setembro de 2016 99 prescrições de pacientes internados há mais de 48 horas na enfermaria cardiológica de um hospital do Rio de Janeiro. As interações medicamentosas foram avaliadas pelo Micromedex®, e os eventos adversos identificados através de rastreadores e analisados por especialistas com uso do Algoritmo de Naranjo, com emprego de estatística descritiva. Resultados: Foram detectadas 18 potenciais interações graves em 22 pares medicamentosos, principalmente sinvastatina x anlodipino (18%) e enoxaparina x clopidogrel (18%). Dos 18 prontuários investigados, foram encontrados quatro rastreadores e definidos três prováveis eventos adversos (16,6%), por alterações hemorrágicas nos pacientes. Conclusão: Interações medicamentosas têm probabilidade de causar danos ao paciente, o que requer implementar barreiras para a segurança do sistema de medicação.

Adverse drug events and the associated factors in patients with chronic Chagas disease

Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Prevalência do uso de medicamentos potencialmente inapropriados ao idoso no Brasil: uma revisão sistemática / Prevalencia del uso de medicamentos potencialmente inapropiados para los ancianos en Brasil: una revisión sistemática / Prevalence use of potentially inappropriate drugs for elderly in Brazil: a sistematic review

O envelhecimento está relacionado, via de regra, ao uso de medicamentos. Esta é uma revisão sistemática sobre as prevalências de uso de medicamento potencialmente perigosos em idosos, em estudos brasileiros, utilizando-se o Critério de Beers. A prevalência variou entre 17 e 98,2% em amostras domiciliares, ambulatoriais, hospitalares e em instituições de longa permanência. Dados que demonstram a necessidade de políticas de enfrentamento aos riscos inerentes ao uso de medicamento pelo paciente idoso no Brasil.

The aging is related with use of drugs. This research is a systematic review about use of potentially inappropriate drugs for elderly evaluated by Beers Criteria. The prevalence's range was 17 to 98,2% on home, ambulatory, hospital or nursing home samples. These data demonstrate that governmental politics are necessary to face the risks of drugs using by elderly in Brazil.

El envejecimiento generalmente está relacionado con el uso de medicamentos. Esta es una revisión sistemática de la prevalencia del uso de drogas potencialmente peligrosas en los ancianos, en estudios brasileños, utilizando el Criterio de Beers. La prevalencia varió entre 17 y 98.2% en muestras de atención domiciliaria, ambulatoria, hospitalaria y de atención a largo plazo. Datos que demuestran la necesidad de políticas para enfrentar los riesgos inherentes al uso de medicamentos por parte de pacientes de edad avanzada en Brasil.

Suspected adverse drug reactions reported for Brazilian children: cross-sectional study / Suspeitas de reações adversas a medicamento relatadas em crianças brasileiras: estudo transversal

ABSTRACT Objective: To assess spontaneous reports of suspected adverse drug reactions in children aged 0-12 years from the Brazilian Health Regulatory Agency between 2008 and 2013. Methods: A cross-sectional study on suspected adverse drug reactions reports related to medicines and health products in children was carried out for a six-year period (2008-2013). Year of report, origin of report by Brazilian state, gender, age, suspected drug, adverse reaction description and seriousness were included in the analysis. The data obtained was compared to the number of pediatric beds in health services and to global data from the VigiBase (World Health Organization). Results: A total of 3330 adverse drug reactions were reported in children in Brazil in the investigated period (54% were in boys). About 28% of suspected adverse drug reactions reports involved 0 to 1-year-old children. Almost 40% of reports came from the Southeast region. Approximately 60% were classified as serious events. There was death in 75 cases. Nearly 30% of deaths involved off-label use; 3875 medicines (465 active substances) were considered suspected drugs. Anti-infective (vancomycin, ceftriaxone, oxacillin, and amphotericin), nervous system (metamizole) and alimentary tract and metabolism medicines were more frequent in reports. Conclusions: The distribution of suspected adverse drug reactions reports by sex and age group corresponded to the profile of children hospitalized in Brazil. Data about seriousness and medicines reported may be useful to encourage regulatory actions and improve the safe use of medicines in children.

RESUMO Objetivo: Analisar relatos espontâneos de suspeitas de Reação Adversa a Medicamento (RAM) em crianças de 0 a 12 anos notificadas pela Agência Nacional de Vigilância Sanitária entre 2008 e 2013. Métodos: Um estudo transversal a partir de notificações de suspeitas de RAM relacionadas a medicamentos e produtos para a saúde em crianças foi realizado por um período de seis anos (2008-2013). O ano da notificação, a origem do relato por estado brasileiro, sexo, idade, o medicamento suspeito, a descrição da reação adversa e a gravidade foram incluídos na análise, bem como o número de leitos nos serviços de saúde e dados global da VigiBase. Resultados: Um total de 3330 reações adversas foram relatadas em crianças no Brasil no período investigado (54% em meninos). Cerca de 28% dos relatos de suspeitas de RAM envolveram crianças de 0 a 1 ano de idade. Quase 40% dos relatos vieram da região Sudeste. Aproximadamente 60% foram classificados como eventos graves. Houve ocorrência de morte em 75 casos. Quase 30% das mortes envolveram o uso off-label dos medicamentos. Um total de 3875 medicamentos (465 substâncias ativas) foram considerados fármacos suspeitos. Medicamentos anti-infecciosos (vancomicina, ceftriaxona, oxacilina e anfotericina), com ação no sistema nervoso (dipirona) e no trato digestivo foram os mais frequentemente notificados. Conclusões: As notificações de suspeitas de RAM por sexo e faixa etária corresponderam ao perfil de crianças hospitalizadas no Brasil. Os dados sobre gravidade e medicamentos relatados podem ser úteis para encorajar ações reguladoras e melhorar o uso seguro de medicamentos em crianças.