RESUMO

Introduction: The World Health Organization recommends prioritizing safe and effective drugs proven by clinical or epidemiological studies. However, in population groups with little research, a drug can be used for an indication or pharmaceutical form different from that approved by the regulatory agency (off-label), extrapolating data from studies in adults and exposing pediatric patients. to develop an Adverse Drug Reaction (ADR) due to safety considerations that have not been systematically studied. Intravenous immunoglobulin (IVIg), a high-cost drug, is used with scant evidence in some low-prevalence pathologies. This paper describes and analyzes the off-label use of IVIg at the J. P. Garrahan Pediatric Hospital. Methods: Observational, descriptive, prospective study on off-label indications of IVIg. The sampling technique was non-probabilistic and for convenience during 7 months. Results: 305 IVIg infusions were studied, corresponding to 111 patients. The indication classification showed that 22% (n=67) of the infusions were off-label. In neurology there was a higher percentage of off-label indications (46%) and within them 45% corresponded to the use in neurological disorders. 81% of the doses indicated off-label were in the range 0.8-1g/kg. The off-label infusions presented 61.5% (n=8) of the ADRs. Those from the Neurology service represented 87.5%; 75% being from the "Neurological disorders" group. Conclusion: In some cases, IVIg was indicated in an off-label manner, finding a statistically significant relationship with the appearance of ADR. This finding motivates the proposition of new hypotheses to carry out more studies.

Introducción: La Organización Mundial de la Salud recomienda priorizar fármacos seguros y eficaces comprobados mediante estudios clínicos o epidemiológicos. Sin embargo, en grupos poblacionales con escasa investigación, un fármaco puede utilizarse para una indicación o, forma farmacéutica diferente a la aprobada por la agencia reguladora ("off label"), extrapolando datos provenientes de estudios en adultos y, exponiendo a los pacientes pediátricos a desarrollar una Reacción Adversa Medicamentosa (RAM) por consideraciones de seguridad no estudiadas sistemáticamente. Inmunoglobulina G endovenosa (IgG EV), medicamento de alto costo, es utilizado con escasa evidencia en algunas patologías poco prevalentes. Este trabajo describe y analiza el uso "off label" de IgG EV en el Hospital de Pediatría J. P. Garrahan. Métodos: Estudio observacional, descriptivo, prospectivo sobre indicaciones "off label" de IgG EV. La técnica de muestreo fue no probabilística y por conveniencia durante 7 meses. Resultados: Se estudiaron 305 infusiones de IgG EV que correspondieron a 111 pacientes. La clasificación de la indicación mostró que 22% (n=67) de las infusiones fueron "off label". En neurología hubo mayor porcentaje de indicaciones "off label" (46%) y dentro de ellas el 45% correspondió al uso en desórdenes neurológicos. El 81% de dosis indicadas "off label" estuvieron en rango 0,8-1g/kg. Las infusiones indicadas "off label" presentaron el 61.5% (n=8) de las RAM. Las del servicio de Neurología, representaron el 87,5 %, siendo 75% del grupo "Desórdenes neurológicos". Conclusión: En algunos casos IgG EV fue indicada en forma "off label", encontrándose una relación estadísticamente significativa con la aparición de RAM. Este hallazgo motiva al planteo de nuevas hipótesis para realizar más estudios.

Assuntos

RESUMO

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Assuntos

RESUMO

ABSTRACT Objective: To analyze the prevalence of off-label and unlicensed prescriptions for a population of neonates admitted to the Neonatal Intensive Care Unit in a hospital in southern Santa Catarina. Methods: Observational study with a cross-sectional design. All neonates admitted to the Intensive Care Unit during the period from March 2020 to March 2021 were included. Data collection was performed through a questionnaire made by the authors and the classification of drugs based on the Electronic Drug Description (Bulário Eletrônico) of the Brazilian Health Regulatory Agency and Drug Dex-Micromedex. Results: Data from 296 neonates were evaluated. The prevalence was 50,7% for prescribing off-label medications and 37,2% for unlicensed medications. The use of drugs was higher in preterm neonates, with low birth weight, 1st minute Apgar between 6-8, 5th minute Apgar between 7-8, and in need of invasive procedures. The most used off-label drugs were ampicillin, gentamicin and fentanyl (92.6, 92.0 and 26.6%, respectively), whereas the most used unlicensed drugs were caffeine, phenobarbital and bromopride (78.1, 16.3 and 10.9%, respectively). Conclusions: This study showed a large percentage of prescriptions made in the off-label (50.7%) and unlicensed (37.2%) form in the Neonatal Intensive Care Unit, corroborating the worrying world scenario. The most exposed neonates were precisely the most vulnerable ones and, among the most commonly prescribed medications, ampicillin and gentamicin stood out in off-label form and caffeine in unlicensed form.

RESUMO Objetivo: Analisar a prevalência de prescrições off-label e não licenciadas uma população de neonatos internados na Unidade de Terapia Intensiva Neonatal em um hospital ao sul de Santa Catarina. Métodos: Estudo observacional com delineamento transversal. Foram incluídos todos os neonatos admitidos na Unidade de Terapia Intensiva durante o período de março de 2020 a março de 2021. A coleta de dados foi realizada a partir de questionário elaborado pelos autores, e a classificação dos medicamentos, com base no Bulário Eletrônico da Agência Nacional de Vigilância Sanitária e no Drug Dex-Micromedex. Resultados: Foram avaliados dados de 296 neonatos. A prevalência foi de 50,7% para prescrição de medicações off-label e 37,2% para medicações não licenciadas. O uso dos fármacos foi maior em neonatos pré-termo, com baixo peso ao nascer, Apgar de 1o minuto entre 6-8, Apgar de 5o minuto entre 7-8, e com necessidade de procedimentos invasivos. Os fármacos off-label mais utilizados foram a ampicilina, gentamicina e fentanil (92,6, 92 e 26,6%, respectivamente), já os fármacos não licenciados mais utilizados foram a cafeína, fenobarbital e bromoprida (78,1, 16,3 e 10,9%, respectivamente). Conclusões: O estudo demonstrou grande porcentagem de prescrições realizadas de forma off-label (50,7%) e não licenciada (37,2%) na Unidade de Terapia Intensiva Neonatal de análise, corroborando o preocupante cenário mundial. Os neonatos mais expostos foram justamente aqueles mais vulneráveis e, entre as medicações mais utilizadas, destacam-se a ampicilina e a gentamicina de modo off-label e a cafeína de modo não licenciado.

RESUMO

Resumo Estudo ecológico com objetivo de determinar o consumo de naltrexona em baixa dose (LDN) nas 26 capitais brasileiras e Distrito Federal e acompanhar a tendência entre os anos de 2014 e 2020. A coleta de dados da dispensação de naltrexona manipulada, se deu por meio do Sistema Nacional de Gerenciamento de Produtos Controlados, publicizado em 2020, considerando-se baixa dose prescrições de até 5 mg. O cálculo dos coeficientes de dispensação utilizou as estimativas populacionais do Instituto Brasileiro de Pesquisa Geografia e Estatística. Utilizou-se análise estatística descritiva e de regressão generalizada de Prais-Winsten para a série temporal. As tendências observadas foram classificadas em crescentes, estáveis ou decrescentes, com intervalo de confiança de 95% e nível de significância de 5%. Os resultados demonstraram maiores coeficientes de consumo de LDN nas regiões Centro-Oeste, Sul e Sudeste e menores nas Norte e Nordeste. Observou-se dispensação de LDN crescente em 55,6% das capitais, estacionária em 44,4% e ausência de coeficientes decrescentes. Apesar das evidências limitadas quanto à farmacoterapia de LDN e da sua prescrição off-label, os dados demonstram que a prescrição, dispensação e consumo vem crescendo no Brasil, com ênfase nas regiões centro-sul do país.

Abstract The scope of this paper is an ecological study to determine the consumption of low-dose naltrexone (LDN) in the 26 Brazilian capitals and the Federal District and monitor the trend between the years 2014 to 2020. Data collection on the dispensation of manipulated naltrexone was done through the National Management System of Controlled Products, published in 2020, considering low-dose prescriptions of up to 5 mg. The calculation of the dispensation coefficients used the population estimates of the Brazilian Institute of Geography and Statistics. Descriptive statistical analysis and generalized Prais-Winsten regression analysis were used for the time series analysis. The trends observed were classified as increasing, stable, or decreasing, with a 95% confidence interval and 5% significance level. The results showed higher LDN consumption coefficients in the Mid-West, South and Southeast regions and lower coefficients in the North and Northeast. Increasing dispensation of LDN was observed in 55.6% of the capitals, being stationary in 44.4%, with no decreasing coefficients. Despite the limited evidence regarding LDN pharmacotherapy and its off-label prescription, the data show that prescription, dispensing, and consumption have been on the increase in Brazil, with emphasis on the central-south regions of the country.

RESUMO

Introducción. En las unidades de cuidados intensivos pediátricos, se utiliza gran cantidad de medicamentos, muchos prescritos fuera de las condiciones establecidas en su ficha técnica (prescripciones off-label y unlicensed). El objetivo de este estudio fue describir el uso de medicamentos y estimar la prevalencia de fármacos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de tercer nivel español. Población y métodos. Estudio transversal, observacional, de una cohorte de niños ingresados en una unidad de cuidados intensivos pediátricos. El estudio se llevó a cabo en 2017. Se revisó cada fármaco prescrito, sus condiciones de uso y administración. Además, se analizaron las fichas técnicas de los fármacos implicados con la finalidad de identificar si el uso de los medicamentos se realizaba según sus condiciones de autorización, o bien se hacía fuera de prospecto (off-label) o como unlicensed. Resultados. La muestra fue de 97 pacientes. El 74,2 % (n = 72) de los pacientes recibieron algún fármaco off-label o unlicensed. El 23,8 % (n = 243) de las prescripciones fueron off-label y el 8,7 % (n = 89), unlicensed. El subanálisis realizado por grupos de edad mostró que el grupo de edad que recibió mayor número de prescripciones totales (n = 611) y el mayor porcentaje de fármacos prescritos en condiciones off-label y/o unlicensed (38,4 %) fue el de menores de 2 años. Conclusiones. La prescripción de fármacos off-label y/o unlicensed es una práctica habitual en la unidad de cuidados intensivos pediátricos. Este estudio permite documentar la complejidad de la terapéutica en niños.

Introduction. In pediatric intensive care units, a large number of drugs are used, many of which are prescribed for condition beyond those established in their summary of product characteristics (off-label and unlicensed drug prescriptions). The objective of this study was to describe drug use and estimate the prevalence of off-label and unlicensed drugs in a pediatric intensive care unit of a tertiary care Spanish hospital. Population and methods. Cross-sectional, observational study with a single cohort of children admitted to a pediatric intensive care unit. The study was conducted in 2017. Each drug prescription, its conditions of use and administration were reviewed. In addition, the summary of product characteristics of drugs used were analyzed in order to identify whether they were used according to their conditions of authorization, or whether they were used in an off-label or unlicensed manner. Results. The sample included 97 patients. At least one off-label or unlicensed drug was administered to 74.2% (n = 72) of patients; 23.8% (n = 243) corresponded to off-label prescriptions and 8.7% (n = 89), unlicensed prescriptions. A sub-analysis by age group showed that the age group that received a higher number of total prescriptions (n = 611) and a higher percentage of off-label and/or unlicensed drug prescriptions (38.4%) was under 2 years of age. Conclusions. Off-label and/or unlicensed drug prescription is a common practice in the pediatric intensive care unit. This study allowed us to document the complexity of therapeutics in children.

Assuntos

RESUMO

Cryptococcosis is an opportunistic mycosis that mainly affects immunosuppressed patients. The treatment is a combination of three antifungal agents: amphotericin B, 5-flucytosine and fluconazole. However, these drugs have many disadvantages, such as high nephrotoxicity, marketing bans in some countries and fungal resistance. One of the solutions to find possible new drugs is pharmacological repositioning. This work presents repositioned drugs as an alternative for new antifungal therapies for cryptococcosis. All the studies here were performed in vitro or in animal models, except for sertraline, which reached phase III in humans. There is still no pharmacological repositioning approval for cryptococcosis in humans, though this review shows the potential of repurposing as a rapid approach to finding new agents to treat cryptococcosis.

Assuntos

RESUMO

Introduction. In pediatric intensive care units, a large number of drugs are used, many of which are prescribed for condition beyond those established in their summary of product characteristics (off-label and unlicensed drug prescriptions). The objective of this study was to describe drug use and estimate the prevalence of off-label and unlicensed drugs in a pediatric intensive care unit of a tertiary care Spanish hospital. Population and methods. Cross-sectional, observational study with a single cohort of children admitted to a pediatric intensive care unit. The study was conducted in 2017. Each drug prescription, its conditions of use and administration were reviewed. In addition, the summary of product characteristics of drugs used were analyzed in order to identify whether they were used according to their conditions of authorization, or whether they were used in an off-label or unlicensed manner. Results. The sample included 97 patients. At least one off-label or unlicensed drug was administered to 74.2% (n = 72) of patients; 23.8% (n = 243) corresponded to off-label prescriptions and 8.7% (n = 89), unlicensed prescriptions. A sub-analysis by age group showed that the age group that received a higher number of total prescriptions (n = 611) and a higher percentage of off-label and/or unlicensed drug prescriptions (38.4%) was under 2 years of age. Conclusions. Off-label and/or unlicensed drug prescription is a common practice in the pediatric intensive care unit. This study allowed us to document the complexity of therapeutics in children.

Introducción. En las unidades de cuidados intensivos pediátricos, se utiliza gran cantidad de medicamentos, muchos prescritos fuera de las condiciones establecidas en su ficha técnica (prescripciones off-label y unlicensed). El objetivo de este estudio fue describir el uso de medicamentos y estimar la prevalencia de fármacos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de tercer nivel español. Población y métodos. Estudio transversal, observacional, de una cohorte de niños ingresados en una unidad de cuidados intensivos pediátricos. El estudio se llevó a cabo en 2017. Se revisó cada fármaco prescrito, sus condiciones de uso y administración. Además, se analizaron las fichas técnicas de los fármacos implicados con la finalidad de identificar si el uso de los medicamentos se realizaba según sus condiciones de autorización, o bien se hacía fuera de prospecto (off-label) o como unlicensed. Resultados. La muestra fue de 97 pacientes. El 74,2 % (n = 72) de los pacientes recibieron algún fármaco off-label o unlicensed. El 23,8 % (n = 243) de las prescripciones fueron off-label y el 8,7 % (n = 89), unlicensed. El subanálisis realizado por grupos de edad mostró que el grupo de edad que recibió mayor número de prescripciones totales (n = 611) y el mayor porcentaje de fármacos prescritos en condiciones off-label y/o unlicensed (38,4 %) fue el de menores de 2 años. Conclusiones. La prescripción de fármacos off-label y/o unlicensed es una práctica habitual en la unidad de cuidados intensivos pediátricos. Este estudio permite documentar la complejidad de la terapéutica en niños.

Assuntos

RESUMO

Introducción: indicaciones off label, estrecho margen terapéutico, variabilidad farmacocinética, interacciones farmacológicas constituyen algunos de los problemas a abordar en el uso crónico de antiepilépticos (AE). Caracterizar su perfil de uso es necesario para promover su prescripción racional. Objetivo: Describir el perfil de uso de AE en menores de 15 años hospitalizados en el Centro Hospitalario Pereira Rossell entre 1/07/2020 y 31/12/2020. Material y método: estudio descriptivo, de menores de 15 años hospitalizados en cuidados moderados en tratamiento con AE. Variables: tipo y número de AE, motivo de la indicación, vía de administración, dosis, uso asociado con psicofármacos, adherencia. Resultados: recibían AE 113 pacientes, mediana edad 7 años, 50,4% sexo femenino. Motivo de la indicación: epilepsia (grupo A) 50,4% y otras patologías (grupo B) 49,6%. Mediana de edad: 2,7 años grupo A vs. 11,5 años grupo B. El AE más indicado fue levetiracetam en el grupo A (35%) y ácido valproico en el grupo B (35,7%). La asociación con psicofármacos se registró en 8,7% grupo A vs. 44,6% en el grupo B. Conclusiones: predominó el uso de levetiracetam en pacientes epilépticos. La mitad de los pacientes recibieron AE para patologías diferentes a la epilepsia, mayoritariamente psiquiátricas. En este grupo predominó el uso de ácido valproico. El análisis de esta serie permite una aproximación al conocimiento del perfil de uso de AE en los niños asistidos en este centro, y por tanto de los principales problemas a abordar. Futuros estudios multicéntricos con población ambulatoria son necesarios para mejorar el conocimiento y contribuir al uso racional de los mismos.

Introduction: off-label prescription, narrow therapeutic margin, pharmacokinetic variability, drug interaction, are some of the problems to consider in the chronic use of antiepileptic drugs (AEDs). It is necessary to characterize their utilization profile in order to promote rational prescription. Objective: to describe the utilization profile of AEDs in children under 15 years of age hospitalized at the Pereira Rossell Pediatric Hospital from 7/01/2020 to 12/31/2020. Material and Methods: descriptive study of children under 15 years of age hospitalized in moderate care units receiving treatment with AEDs. Variables: type and number of AEDs, reason for the prescription, dose, associated use of psychotropic drugs, compliance. Results: 113 patients received AEDs, median age 7 years, 50.4% females. Reason for prescription; epi- lepsy (group A) 50.4%, other pathologies (group B) 49.6%. Median age in group A 2.7 years, versus 1.1.5 years in group B. Most frequently prescribed AEDs was levetiracetam in group A (35%) and valproic acid in group B (37,7%). Association with psychotropic drugs was present in 8.7% of group A versus 44.6% of group B. Conclusions: levetiracem use was predominant in epileptic patients. Half of the patients received AEDs for pathologies other than epilepsy, mostly psychiatric. In this group the use of valproic acid was predominant. Analysis of this series enables an approximation to the understanding of the profile of AEDs use in children assisted at this Hospital, and there- fore an approximation to the problems to be considered. Future multicenter studies with an outpatient population are necessary to expand our knowledge and to contribute to a rational use of these drugs.

Introdução: indicações off-label, margem terapêutica estreita, variabilidade farmacocinética, interações farmacológicas são alguns dos problemas a serem abordados no uso crônico de drogas antiepilépticas (EA). Caracterizar seu perfil de uso é necessário para promover sua prescrição racional. Objetivo: descrever o perfil de utilização da AE em crianças menores de 15 anos internadas no Centro Hospitalar Pereira Rossell entre 01/07/2020 e 31/12/2020. Material e Métodos: estudo descritivo de crianças menores de 15 anos internadas em cuidados moderados em tratamento de EA. Variáveis: tipo e número de EAs, motivo da indicação, via de administração, dose, uso associado a psicotrópicos, adesão. Resultados: 113 pacientes receberam EA, com meia idade de 7 anos, 50,4% do sexo feminino. Motivo da indicação: epilepsia (grupo A) 50,4% e outras patologias (grupo B) 49,6%. Mediana de idade: 2,7 anos grupo A vs. 11,5 anos grupo B. O EA mais indicado foi Levetiracetam no grupo A (35%) e ácido valpróico no grupo B (35,7%). A associação com psicotrópicos foi registrada em 8,7% do grupo A vs. 44,6% no grupo B. Conclusões: o uso de Levetiracetam em pacientes epilépticos predominou. A metade dos pacientes recebeu AE por outras patologias que não foram a epilepsia, principalmente psiquiátricas. Nesse grupo, predominou o uso do ácido valpróico. A análise desta série permite aproximar o conhecimento do perfil de uso da AE nas crianças atendidas nesse centro e, portanto, a aproximação aos principais problemas a serem abordados. Futuros estudos multicêntricos com população ambulatorial são necessários para aprimorar o conhecimento e contribuir para sua utilização racional.

Assuntos

RESUMO

ABSTRACT Objective: To analyze the use of ivermectin as COVID-19 prevention method by the population of Mato Grosso in 2020. Methods: This is a home-based survey, carried out between September and October 2020, in 10 pole cities of the socioeconomic regions of State. The use of ivermectin was evaluated through the question: "Did you take ivermectin to prevent COVID-19?". Sociodemographic variables (sex, age group, education, family income), current work situation, being benefitted by government financial programs, as well as symptoms, seroprevalence of antibodies against SARS-CoV-2, and previous diagnosis of COVID-19 were evaluated. Prevalence and their associations were estimated using the chi-square test. Results: 4.206 individuals were evaluated for prevalence of ivermectin use; 58.3% of the individuals responded positively, this rate being higher in the municipalities of the western region of the state (66.6%). There was no significant difference between sexes, but the prevalence was higher among people aged 50-59 years (69.7%), who were white (66.5%), with complete higher education or more (68.8%) and higher family income (≥3 minimum wages-64.2%). The use of this drug was even higher among participants who considered their knowledge of the disease good or very good (65.0%), who reported having symptoms of COVID-19 (75.3%), and who had been previously diagnosed with the disease (91.2%). Conclusion: There was a high prevalence of use of ivermectin as a method to prevent covid-19 by the population of Mato Grosso, indicating the need for strategies to inform the population about the risks of off-label use of drugs and to combat the advertising of drugs that are ineffective against COVID-19.

RESUMO Objetivo: Analisar a utilização de ivermectina como prevenção da COVID-19 pela população de Mato Grosso em 2020. Métodos: Trata-se de um inquérito de base domiciliar, realizado entre setembro e outubro de 2020, em dez municípios-polos das regiões socioeconômicas do estado. O uso da ivermectina foi avaliado por meio da pergunta: "Tomou ivermectina para prevenir a COVID-19?". Foram avaliadas as variáveis sociodemográficas (sexo, faixa etária, escolaridade, renda familiar), a situação de trabalho atual, o recebimento de benefícios financeiros governamentais, bem como sintomas, a soroprevalência de anticorpos contra SARS-CoV-2 e o diagnóstico prévio de COVID-19. As estimativas de prevalência e suas associações foram realizadas por meio do teste χ2. Resultados: Foram analisados 4.206 indivíduos, e a prevalência de uso de ivermectina foi de 58,3%, sendo maior nos municípios da região Oeste (66,6%). Não houve diferença significativa entre os sexos, a prevalência foi maior na da faixa etária de 50-59 anos (69,7%), em pessoas brancas (66,5%), com ensino superior completo ou mais (68,8%) e maior renda familiar (≥3 salários-mínimos — 64,2%). A utilização do medicamento ainda foi maior entre os que consideraram seu conhecimento sobre a doença como bom ou muito bom (65,0%), entre os que referiram ter apresentado sintomas de COVID-19 (75,3%) e que foram diagnosticados com a doença previamente (91,2%). Conclusão: Verifica-se a elevada a prevalência do uso de ivermectina para a prevenção da COVID-19 pela população de Mato Grosso, indicando a necessidade de estratégias para informar a população sobre os riscos do uso off-label de medicamentos e combater a publicidade de medicamentos sem eficácia contra COVID-19.

RESUMO

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

Assuntos

RESUMO

ABSTRACT Objective: To analyze the profile of the compounded cardiovascular medicines prescribed in neonatology in Brazil. Data source: An integrative bibliographic review was carried out, including studies published in the last 20 years. The used descriptors were: Intensive Care Neonatal, Off-Label Use, Pharmaceutical Preparations, in the databases Virtual Health Library (VHL), PubMed, and Scientific Electronic Library Online (SciELO). Review articles and guidelines were excluded. The quality of the evidence was analyzed, and 10 articles were selected to integrate the study. Data synthesis: The profile of routine prescrption in the neonatal unit was evaluated. The main cardiovascular medications prescribed as compounding formulation were: Spironolactone, Captopril, Furosemide, Hydrochlorothiazide, Propranolol, Amiodarone, Nifedipine, Carvedilol, Digoxin, Enalapril, Epinephrine, and Hydralazine. The drugs were obtained from adaptations of dosage forms, through the transformation of capsules or tablets into liquid formulations, as a solution, suspension, or syrup, as well as in the form of solutions prepared from active pharmaceutical ingredients. The compounding of medications made drug therapy possible in neonatology, considering that such medications do not have registration of the oral liquid dosage form in the country, despite being part of the List of Essential Medicines for Children of the Word Health Organization. Conclusions: It was possible to analyze the profile of compounded cardiovascular medicines prescribed in neonatology in Brazil. The results showed the need for the development of medications suitable for the neonatal population, and the standardization of operational procedures for preparing extemporaneous formulations in neonatology to increase drug safety.

RESUMO Objetivo: Analisar o perfil dos medicamentos cardiovasculares manipulados prescritos em neonatologia no Brasil. Fontes de dados: Foi realizada uma revisão bibliográfica integrativa, incluindo estudos publicados nos últimos 20 anos. As palavras-chave utilizadas foram: intensive care neonatal, off-label use, pharmaceutical preparations, nos bancos de dados da Biblioteca Virtual em Saúde (BVS), PubMed e Biblioteca Eletrônica Científica Online (SciELO). Os artigos de revisão e diretrizes foram excluídos. A qualidade da evidência foi analisada, e foram selecionados 10 artigos para integrar o estudo. Síntese dos dados: Todos os estudos possibilitaram a avaliação do perfil de prescrição na rotina da unidade. Os principais fármacos cardiovasculares, prescritos em formulação extemporânea, foram espironolactona, captopril, furosemida, hidroclorotiazida, propranolol, amiodarona, nifedipina, carvedilol, digoxina, enalapril, epinefrina e hidralazina. Os medicamentos foram obtidos mediante adaptações de formas farmacêuticas, por meio da transformação de cápsulas ou comprimidos em formulações líquidas, como solução, suspensão ou xarope, assim como também na forma de soluções preparadas com base nos insumos farmacêuticos ativos. A manipulação de medicamentos tornou possível o tratamento medicamentoso em neonatologia, uma vez que tais medicamentos não possuem registro da forma farmacêutica líquida oral no país, apesar de integrarem a lista de medicamentos essenciais em pediatria da Organização Mundial da Saúde. Conclusões: Foi possível analisar o perfil dos medicamentos cardiovasculares manipulados prescritos na neonatologia no Brasil. Os resultados evidenciaram a necessidade do desenvolvimento de medicamentos adequados à população neonatal e à padronização dos procedimentos operacionais do preparo de formulações extemporâneas na neonatologia, para aumentar a segurança dos medicamentos.

RESUMO

BACKGROUND: Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. METHODS: A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. RESULTS: One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. CONCLUSIONS: Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.

Assuntos

RESUMO

INTRODUCTION: Tigecycline is an antimicrobial agent, approved for the treatment of complicated skin and soft tissue infections, hospital-acquired and community-acquired pneumonia, intra-abdominal infections and anaerobic or atypical infections. OBJECTIVE: To describe the use of tigecycline in a teaching hospital and to compare data from patients who had their prescriptions audited by the hospital infection committee with those who did not have audited prescriptions. METHODS: Retrospective observational cohort study conducted at a teaching hospital from April 2012 to March 2014 including patients who received tigecycline. Demographic variables, comorbidities, microbiological findings, prescribed antibiotics and technical opinions issued by the Hospital Infection Control Service were collected. RESULTS: 71 patients were included, aged between 13 and 92 years, 63.4% were male and 56.3% were non-white. Tigecycline was the first antimicrobial choice in 19.7% (14/71) of the cases, while the use associated with other antibiotics was observed in 66.2% (45/71) of the prescriptions. mainly with meropenem (28.9%). Empirical use was performed in 69.0% of cases, after culture and the antibiogram in 31.0% and off label use in 81.7%. The microorganisms frequently identified by the culture tests were Enterococcus faecalis (17.6%), Pseudomonas aeruginosa (14.7%) and Klebsiella penumoniae (11.8%). CONCLUSION: The study demonstrated that empirical and off label use is common in clinical practice and few prescriptions were guided by the results of the culture and the antibiogram, demonstrating the need for prescribers to evaluate the benefits/ risks of using this antibiotic, risk of resistance, adverse effects and drug interactions, in addition to cost.

INTRODUÇÃO: A tigeciclina é agente antimicrobiano, aprovada para o tratamento de infecções complicadas na pele e tecidos moles, pneumonia hospitalar e adquirida na comunidade, infecções intra-abdominal e infecções anaeróbias ou atípicas. OBJETIVO: Descrever o uso da tigeciclina em hospital de ensino e comparar dados de pacientes que tiveram suas prescrições auditadas pela comissão de infecção hospitalar com os que não tiveram prescrições auditadas. MÉTODOS: Estudo de coorte retrospectivo observacional realizado em hospital de ensino de abril de 2012 a março de 2014 incluindo pacientes que receberam tigeciclina. Foram coletadas variáveis ​​demográficas, comorbidades, achados microbiológicos, antibióticos prescritos e pareceres técnicos emitidos pelo Serviço de Controle de Infecção Hospitalar. RESULTADOS: Foram incluídos 71 pacientes, com idade entre 13 e 92 anos, 63,4% eram do sexo masculino e 56,3% eram não brancos. A tigeciclina foi primeira escolha antimicrobiana em 19,7% (14/71) dos casos, enquanto o uso associado a outros antibióticos foi observado em 66,2% (45/71) das prescrições. principalmente com meropenem (28,9%). O uso empírico foi realizado em 69,0% dos casos, após cultura e o antibiograma em 31,0% e o uso off label em 81,7%. Os microrganismos frequentemente identificados pelos testes de cultura foram Enterococcus faecalis (17,6%), Pseudomonas aeruginosa (14,7%) e Klebsiella penumoniae (11,8%). CONCLUSÃO: O estudo demonstrou que o uso empírico e off label é comum na prática clínica e poucas prescrições foram orientadas pelos resultados da cultura e do antibiograma, demonstrando necessidade de prescritores avaliarem os benefícios/riscos do uso desse antibiótico, risco de resistência, efeitos adversos e interações medicamentosas, além do custo.

Assuntos

RESUMO

Major advances in sequencing technologies and targeted therapies have accelerated the incorporation of oncology into the era of precision medicine and "biomarker-driven" treatments. However, the impact of this approach on the everyday clinic has yet to be determined. Most precision oncology reports are based on developed countries and usually involve metastatic, hard-to-treat or incurable cancer patients. Moreover, in many cases race and ethnicity in these studies is commonly unreported and real-world evidence in this topic is scarce. Herein, we report data from a total of 202 Chilean advanced stage refractory cancer patients. Retrospectively, we collected patient data from NGS tests and IHC in order to determine the proportion of patients that would benefit from targeted treatments. Overall >20 tumor types were included in our cohort and 37% of patients (n = 74) displayed potentially actionable alterations, including on-label, off-label and immune checkpoint inhibitor recommendations. Our findings were in-line with previous reports such as the cancer genome atlas (TCGA). To our knowledge, this is the first report of its kind in Latin America delivering real-world evidence to estimate the percentage of refractory tumor patients that might benefit from precision oncology. Although this approach is still in its infancy in Chile, we strongly encourage the implementation of mutational tumor boards in our country in order to provide more therapeutic options for advanced stage refractory patients.

RESUMO

Ours is a cross-sectional, descriptive, retrospective study evaluating the extent of off-label prescribing for patients attending a university paediatric outpatient department in Goiás, Brazil. 391 patients were treated in the outpatient, and 668 medicines were prescribed. Of these, 70.4% followed the terms of the marketing authorization; 0.3% were unlicenced, and 11% were off-label. Dose was the main factor in off-label prescribing. Infants (0-2 years) received 37.8% of the off-label prescriptions. Vitamins and drugs for the treatment of respiratory diseases were the most prevalent culprits. Of the total prescriptions, 23 different drugs were defined as off-label. Salbutamol was the most prescribed (41.9%). Owing to practical and legal difficulties in carrying out clinical trials, medicines are inadequately studied in children; cooperation between industry, regulatory authorities, and healthcare professionals is required to improve treatment safety. Our results may help guide clinical researcher on off-label prescripting in future trials.

Assuntos

RESUMO

In the paediatric population, paticulary in the field of child and adolescent psychiatry, off-label indications are the rule rather than the exception. This may occur when a drug is indicated for a pathology, age, route of administration or treatment length other than those described in the product label. Argentina, unlike other countries, has no explicit regulation on off-label prescribing. Therefore, the prescription of a medicine in a manner different from that approved by the National Administration of Medicines, Food and Medical Technology (ANMAT) does not have a regulatory framework regarding the conditions that must be met at the time of treatment. Although off-label use is not prohibited, it carries an additional risk. In order to encourage research in paediatrics, regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have introduced legislative reform. The following paper will review the current framework of the regulatory agencies that are relevant to the paediatric population and will analyse criteria to guide physicians in the rational use of off-label pharmacotherapy.

En la población pediátrica y particularmente en el ámbito de la psiquiatría infanto-juvenil, las indicaciones off-label representan una regla más que una excepción. Esta práctica puede ocurrir cuando un fármaco se indica en una patología, rango terapéutico, edad, vía de administración o duración distinta a las que se describen en el prospecto. Argentina, a diferencia de otros países, no tiene una regulación expresa en relación a la prescripción off-label. Por lo tanto, la indicación de un medicamento de manera diferente a la aprobada por la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) no posee un marco normativo en lo referente a las condiciones que deben ser cumplidas al momento de ese acto médico. Si bien el uso off-label no se encuentra prohibido, conlleva un riesgo adicional. Con el objetivo de fomentar la investigación en pediatría, las agencias reguladoras como la Food and Drug Administration (FDA) y la European Medicines Agency (EMA) han introducido reformas legislativas. En el siguiente trabajo se revisarán las normativas vigentes de las agencias reguladores que competen a la población pediátrica y se analizarán criterios que orienten al médico al uso racional de la farmacoterapia off-label.

Assuntos

RESUMO

As percepções e o uso de metilfenidato entre universitários foram investigados em estudo descritivo realizado em duas etapas. A primeira, quantitativa, foi realizada por meio do preenchimento de um questionário semiestruturado on-line. Para a segunda etapa, qualitativa, foi realizado um grupo focal. Dos 337 participantes da primeira etapa, 14,5% relataram usar o metilfenidato. Entre os usuários, a prevalência de uso sem prescrição foi maior para o sexo masculino (65,3%), após ingresso na faculdade (57,1%), e 61,2% relataram eventos adversos. O principal motivo de uso foi o doping intelectual (65,3%). Já na etapa qualitativa, além de reforçar os achados anteriores, foram identificados tópicos temáticos como a pressão externa exercida por familiares, sociedade e a rotina universitária. Esses achados apontam para a necessidade de medidas de apoio e orientação aos universitários e de reformulação do processo ensino-aprendizagem.(AU)

This descriptive study investigated the use and perceptions of methylphenidate among university students. The study was conducted in two stages. In the first stage (quantitative), the students completed an online semi-structured questionnaire. The second stage (qualitative) consisted of focus group discussions. Of the 337 participants in the first stage, 14.5% reported using methylphenidate. The prevalence of methylphenidate use without a prescription was greater among men (65.3%) and after starting university (57.1%); 61.2% of the students reported adverse events. The main reason for using the drug was intellectual doping (65.3%). In the qualitative stage, which reinforced the findings of the quantitative stage, we identified themes such as external pressure from family, society and university routine. The findings underline the need to provide student support and advice and reformulate the teaching and learning process.(AU)

Se investigaron las percepciones y el uso del metilfenidato entre universitarios, en un estudio descriptivo realizado en dos etapas. La primera, cuantitativa, se realizó por medio del llenado de un cuestionario semiestructurado online. Para la segunda etapa, cualitativa, se realizó un grupo focal. De los 337 participantes de la primera etapa, el 14,5% relató que usaba metilfenidato. Entre los usuarios, la prevalencia de uso sin prescripción fue mayor para el sexo masculino (65,3%), después del ingreso en la facultad (57,1%) y el 61,2% relataron eventos adversos. El principal motivo de uso fue el dopping intelectual (65,3%). En la etapa cualitativa, además de reforzar los hallazgos anteriores, se identificaron tópicos temáticos tales como la presión externa ejercida por los familiares, la sociedad y la rutina universitaria. Esos hallazgos señalan la necesidad de medidas de apoyo y orientación a los universitarios y de reformulación del proceso enseñanza-aprendizaje.(AU)

Assuntos

RESUMO

A falta de medicamentos contendo bulas prevendo o tratamento de pacientes pediátricos representa um problema frequentemente observado em hospitais, principalmente nos setores de unidade de terapia intensiva (UTI) pediátrica e neonatais. Sabe-se que, para que um tratamento seja considerado seguro e eficaz, uma série de estudos clínicos são necessários, no entanto, relata-se um baixo número dessas pesquisas envolvendo crianças, principalmente devido a questões éticas que dificultam a condução das mesmas. Assim, poucos são os medicamentos que provam ser adequados para o tratamento desses pacientes, tornando necessário recorrer ao uso de medicamentos off-label e não licenciados. Os medicamentos são classificados como off-label quando seu uso se dá de maneira que difere de suas especificações aprovadas, por sua vez, produtos não licenciados são classificados desta forma por não possuírem aprovação para sua comercialização no país ou não possuírem comprovação de segurança e eficácia. O preparo de protocolos de estudo organizados, relato de informações aos pais e à criança de maneira clara e objetiva, aproximação entre pesquisadores e pais para o estabelecimento de uma relação de confiança e a condução das pesquisas em momentos de disponibilidade da família demonstram-se estratégias importantes para facilitar a realização dos ensaios clínicos.

The lack of medicines containing drug information leaflets considering the treatment of pediatric patients is a problem frequently observed in hospitals, especially in the pediatric and neonatal intensive care unit (ICU) sectors. It is known that, for a treatment to be considered safe and effective, a series of clinical studies are necessary; however, a low number of these studies involving children are reported, mainly due to ethical issues that make conducting them difficult. Thus, few drugs prove to be suitable for treating these patients, making it necessary to resort to using off-label and unlicensed drugs. Drugs are classified as off-label when their use differs from their approved specifications, in turn, unlicensed products are classified in this way due to not having approval for marketing in the country or do not have proof of safety and efficacy. Preparation of organized study protocols, reporting information to parents and the child in a clear and objective way, bringing researchers and parents closer to establish a relationship of trust and conducting research at moments when the family is available are important strategies to facilitate conducting clinical trials.

Assuntos

RESUMO

Abstract The objective of this study was to determine the prevalence and describe the factors associated with off-label drug use in an adult intensive care unit (ICU) of a Brazilian hospital. An analytical, cross-sectional, prospective study was conducted in the adult ICU population from March 2018 to May 2018. Off-label use of medication was classified by indication, dosage, route of administration, type and volume of diluent, and duration of administration. Most patients were female (57.89%), non-elderly (56.14%), and had a mean age of 54.44 ± 17.15 years. The prevalence of off-label drug use was 70.31%, but was not associated with the clinical severity of the patients. A statistically significant association was observed between label use of drugs and prescribing potentially inappropriate medicines (PIM). The most common reasons for off-label drug use were therapeutic indication (19.58%) and volume of diluent (23.30%). Drug administration by enteral tubes accounted for the largest number of off-label uses due to route of administration (90.85%). There was a higher prevalence of off-label use of systemic antimicrobials (14.44%) and norepinephrine (9.28%). Our study provided a broad characterization of off-label drug use in an adult ICU and showed why it is important for health professionals to evaluate the specific risks and benefits of this practice

Assuntos

RESUMO

Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via off-label routes. Inhaled roflumilast reportedly improved inflammatory and histopathological changes in asthmatic mice. The current study investigated the effects of oral and rectal roflumilast on trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis in rats, an experimental model resembling human Crohn's disease. Five groups of rats (n=8) were used: normal control, TNBS-induced colitis, and three TNBS-treated colitic groups, which received oral sulfasalazine (500 mg·kg-1·day-1), oral roflumilast (5 mg·kg-1·day-1), or rectal roflumilast (5 mg·kg-1·day-1) for 15 days after colitis induction. Then, the following were assessed: the colitis activity score, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-6 serum levels, colonic length, and myeloperoxidase, malonaldehyde, and glutathione levels. Histological examinations employed H&E, Masson trichrome, and PAS stains in addition to immunostaining for KI-67 and TNF-α. The TNBS-induced colitis rats showed significant increases in disease activity scores, serum TNF-α, IL-2, and IL-6 levels, and colonic myeloperoxidase and malonaldehyde content. They also showed significant decreases in colonic length and glutathione levels in addition to histopathological and immunohistochemical changes. All the treatments significantly improved all these changes. Sulfasalazine provided the greatest improvement, followed by oral roflumilast, and then rectal roflumilast. In conclusion, both oral and rectal roflumilast partially improved TNBS-induced chronic colitis, suggesting the potential of roflumilast as an additional treatment for Crohn's disease.