A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Atención farmacéutica en pacientes con inmunodeficiencia adquirida y/o tuberculosis en el área ambulatoria de un hospital pediátrico / Pharmacovigilance in patients with acquired immunodeficiency and/or tuberculosis in the outpatient area of a pediatric hospital

La Atención farmacéutica (AF) ayuda a los pacientes a alcanzar objetivos terapéuticos reduciendo los problemas relacionados al medicamento (PRM). Objetivos: analizar los PRM en la práctica de la AF a pacientes con inmunodeficiencia adquirida (IDA) y/o tuberculosis (TBC) y evaluar su impacto. Método: estudio, descriptivo, observacional, en el área ambulatoria de Farmacia. Se incluyeron pacientes con IDA y/o TBC con: inicio de tratamiento, polifarmacia, reinternaciones frecuentes, regular/mala adherencia, reacciones adversas a medicamentos (RAM) previas y/o comorbilidades. Se entrevistaron pacientes o cuidadores y se registraron PRM, errores, grados de adherencia y conocimiento farmacoterapéutico, retiro oportuno de medicamentos y parámetros clínicos. Se registró la intervención farmacéutica y entregó material educativo. Se repitieron las mediciones en una segunda entrevista. Resultados: Se estudiaron 54 pacientes (28 con IDA y 26 con TBC). Se realizaron 93 intervenciones (29.9% dirigidas al prescriptor, 27.8% a otros profesionales) y se detectaron 8 RAM y 53 errores (28 IDA y 25 TBC), el principal PRM fue la mala/regular adherencia con bajo porcentaje de conocimiento farmacoterapéutico completo. Después de la AF, en IDA el grado de adherencia tuvo una mejora estadísticamente significativa (p= 0.012), también fue significativa la mejora en el retiro oportuno de la medicación (28.6% a 71.4% p=0.005 IDA). Se obtuvieron resultados favorables de carga viral (CV) en 72% pacientes con IDA y aumento de peso en 92% pacientes con TBC, aunque no fueron estadísticamente significativos. Conclusiones: mediante AF se mejoró la adherencia y la comunicación en pacientes pediátricos con IDA y/o TBC (AU)

Pharmacovigilance (PV) helps patients achieve therapeutic goals by reducing drug-related problems (DRP). Objectives: to analyze DRPs in the practice of PV in patients with acquired immunodeficiency (AIDS) and/or tuberculosis (TB) and to evaluate its impact. Methods: A descriptive, observational study was conducted in the outpatient pharmacy area. Patients with AIDS and/or TB with: treatment initiation, polypharmacy, frequent readmissions, regular/poor adherence, previous adverse drug reactions (ADR) and/or comorbidities were included. Patients or caregivers were interviewed, and DRP, errors, adherence and pharmacotherapeutic knowledge, timely drug withdrawal, and clinical parameters were recorded. The pharmaceutical intervention was recorded and educational material was delivered. Measurements were repeated in a second interview. Results: We studied 54 patients (28 with AIDS and 26 with TB). Ninety-three interventions were performed (29.9% addressed to the drug prescriber, 27.8% to other professionals) and 8 ADRs and 53 errors were detected (28 AIDS and 25 TB). The main DRP was poor/regular adherence together with a low level of complete pharmacotherapeutic knowledge. After PV, in patients with AIDS the degree of adherence statistically significantly improved (p= 0.012). The improvement in timely medication withdrawal was also significant (28.6% vs. 71.4% p=0.005 AID). Favorable viral load results were obtained in 72% of patients with AIDS and weight gain in 92% of patients with TB, although they were not statistically significant. Conclusions: PV improved adherence and communication in pediatric patients with AIDS and/or TB (AU)

Prescripción de fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares / Prescription of cardiotoxic drugs in patients with cardiovascular diseases

Introducción: El uso de fármacos con potencial cardiotóxico para tratar enfermedades no cardiovasculares coexistentes resulta un agravante evitable. Objetivo: Evaluar la prescripción de 5 fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares. Métodos: Se realizó un estudio descriptivo transversal (enmarcado en los estudios de utilización de medicamentos) de marzo a diciembre de 2020 en el Policlínico Santa Cruz (Artemisa, Cuba), en una población de 234 sujetos con enfermedades cardiovasculares que habían sido tratados con domperidona, azitromicina, ciprofloxacina, ibuprofeno y diclofenaco. Las variables estudiadas fueron: sexo, edad, consumo de fármacos cardiotóxicos, motivo de indicación, enfermedades cardiovasculares, forma farmacéutica, dosis diaria, intervalo de las dosis y duración del tratamiento. Se realizó un análisis estadístico descriptivo. Resultados: Los fármacos más prescritos fueron la azitromicina (n= 63), el ibuprofeno (n= 59) y la ciprofloxacina (n= 57). Sus principales motivos de indicación fueron, respectivamente, la neumonía adquirida en la comunidad (38,1 por ciento), las infecciones de piel y tejidos blandos (28,8 por ciento), y las infecciones del tracto urinario (43,8 por ciento). La principal enfermedad cardiovascular fue la hipertensión arterial. Para los 5 fármacos seleccionados se reportó su esquema terapéutico (forma farmacéutica, dosis diaria, intervalo de dosis y duración del tratamiento). Conclusiones: Aunque en todos los casos el motivo de indicación es el adecuado, los fármacos pueden sustituirse por otros de menor riesgo cardiovascular. En su mayoría, los esquemas terapéuticos son correctos, salvo en los casos de la domperidona (duración prolongada) y el diclofenaco (altas dosis)(AU)

Introduction: The use of drugs with cardiotoxic potential to treat coexisting noncardiovascular diseases results in avoidable aggravation. Objective: To assess the prescription of 5 cardiotoxic drugs in patients with cardiovascular disease. Methods: A cross-sectional descriptive study (framed in the studies of drug utilization) was carried out from March to December 2020 in the Policlínico Santa Cruz (Artemisa, Cuba), in a population of 234 subjects with cardiovascular diseases who had been treated with domperidone, azithromycin, ciprofloxacin, ibuprofen and diclofenac. The variables studied were: sex, age, consumption of cardiotoxic drugs, reason for indication, cardiovascular disease, pharmaceutical form, daily dose, dose interval, and duration of treatment. Descriptive statistical analysis was performed. Results: The most prescribed drugs were azithromycin (n= 63), ibuprofen (n= 59) and ciprofloxacin (n= 57). Their main reasons for indication were, respectively, community-acquired pneumonia (38.1 percent), skin and soft tissue infections (28.8 percent), and urinary tract infections (43.8 percent). The main cardiovascular disease was arterial hypertension. For the 5 selected drugs, their therapeutic scheme (pharmaceutical form, daily dose, dose interval and duration of treatment) was reported. Conclusions: Although in all cases the reason for indication was adequate, the drugs can be substituted by others of lower cardiovascular risk. For the most part, the therapeutic regimens are correct, except in the cases of domperidone (prolonged duration) and diclofenac (high doses)(AU)

Prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna en un hospital de referencia en México / Potentially inappropriate prescriptions in geriatric patients hospitalized in the internal medicine department of a referral hospital in Mexico

Resumen Antecedentes: Una prescripción potencialmente inapropiada (PPI) constituye un riesgo de presentar efectos adversos por un fármaco que superan los beneficios de este, pudiendo considerarse como uso inadecuado de medicamentos. Objetivo: Describir la prevalencia de prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna de un hospital de referencia en México. Material y métodos: Diseño descriptivo transversal, con asignación simple de expedientes clínicos de pacientes hospitalizados mayores de 65 años, entre enero de 2016 y agosto de 2017. Se aplicaron los criterios STOPP y START para identificar el número de PPI, cantidad de medicamentos prescritos, presencia, cantidad y tipo de comorbilidades, así como días de estancia hospitalaria. Resultados: Se encontró una prevalencia de 73.3 % de PPI y las principales comorbilidades fueron hipertensión arterial y diabetes mellitus tipo 2. Se cuantificaron 1885 medicamentos prescritos; la estancia hospitalaria media fue de 6.3 días. Conclusiones: Se identificó alta prevalencia de PPI en los pacientes geriátricos hospitalizados, de ahí la importancia de aplicar los criterios STOPP y START y del papel del farmacéutico en la validación de la prescripción antes de la administración de medicamentos.

Abstract Background: Potentially inappropriate prescription (PIP) constitutes a risk for the development of adverse effects of a drug that outweigh its benefits, which can be considered inappropriate medication use. Objective: To describe the prevalence of PIP in geriatric patients hospitalized at the internal medicine department of a referral hospital in Mexico. Material and methods: Cross-sectional, descriptive design, with simple allocation of medical records from patients older than 65 years hospitalized between January 2016 and August 2017. The STOPP/START criteria were applied to identify the number of PIPs, the number of prescribed medications, number and type of comorbidities, as well as days of hospital stay. Results: A prevalence of PIP of 73.3% was identified, with main comorbidities being hypertension and type 2 diabetes mellitus. A total of 1,885 prescribed medications were quantified; mean hospital stay was 6.3 days. Conclusions: A high prevalence of PIP was identified in hospitalized geriatric patients, hence the importance of applying the STOPP/START criteria and of the role of the pharmacist for validating the prescription prior to drug administration.

Reacciones adversas a múltiples antibióticos / Adverse drug reactions to multiple antibiotics

Resumen La información sobre reacciones adversas es fundamental para conocer la seguridad real de los medicamentos comercializados. Existen casos de pacientes con síndrome de intolerancia a múl tiples drogas, una entidad poco reportada, la que puede presentarse cuando en un mismo paciente ocurren reacciones adversas a más de dos medicamentos no relacionados farmacológicamente. Se describe el caso de una mujer con diagnóstico de endocarditis por Staphylococcus aureus multisensible, que cursó con reacciones adversas a cinco antibióticos estructuralmente no relacionados y con mecanismos de acción diferentes, en dos internaciones consecutivas. Las reacciones fueron secundarias a cefazolina (tricitopenia), vancomicina (injuria renal), daptomicina (elevación de creatina fosfoquinasa) y linezolid (hepatotoxicidad) en la primera internación, y a cotrimoxazol (plaquetopenia) en la segunda. En todos los casos se observó daño transitorio en diferentes sistemas de órganos. Finalmente, se otorgó alta hospitalaria con clindamicina sin nuevas intercurrencias hasta finalizar tratamiento. Este caso podría corresponder al síndrome antes mencionado o a una entidad aún no caracterizada.

Abstract Adverse reaction reporting is essential to understand the actual safety of marketed medicines. There are cases of patients with multidrug intolerance syndrome, an under-reported entity, which can occur when adverse reactions to more than two pharmacologically unrelated drugs occur in the same patient. We describe the case of a woman diagnosed with multisensitive Staphylococcus aureus endocarditis who experienced adverse reactions to five structurally unrelated antibiotics with different mechanisms of action in two consecutive hospitalisations. The reactions were secondary to cefazolin (tricytopenia), vancomycin (renal injury), daptomycin (elevated creatine phosphokinase) and linezolid (hepatotoxicity) in the first hospitalization, and to cotrimoxazole (thrombocytopenia) in the second. Transient damage to different organ systems was observed in all cases. Finally, hospital discharge was granted with clindamycin without further intercurrences until treatment was completed. This case could cor respond to the aforementioned syndrome or to an as yet uncharacterized entity.

Reacciones adversas medicamentosas en ancianos de Matanzas, Cuba 2014-2019 / Adverse drug reactions in the elderly of Matanzas, Cuba 2014-2019

Resumen Objetivo: Caracterizar las sospechas de reacciones adversas a medicamentos que se presentaron en los adultos mayores en Matanzas, en el periodo 2014 al 2019. Materiales y Método: Estudio de serie de casos en Farmacovigilancia (FV). Se revisó la base de datos de reportes de sospecha de reacciones adversas a los medicamentos de la Unidad Coordinadora Provincial de Farmacovigilancia, entre 2014 y 2019. Resultados: Se evaluaron un total de 1926 reportes de reacciones adversas por medicamentos en ancianos, representaron el 24,3 % del total. Predominaron las mujeres (56,7 %) y el grupo de edad entre 60 y 69 años (51,4%). Prevaleció la erupción cutánea (13,4 %). Los antimicrobianos y los antiinflamatorios no esteroideos, fueron los que se asociaron más con las RAM en piel, así como del sistema digestivo. La tos estuvo relacionada con el captopril. Predominaron las reacciones adversas por medicamentos de baja frecuencia (55,2%), moderadas (83,8%) y las probables (77,1%) según imputabilidad. Conclusiones: El perfil de seguridad en ancianos en la provincia de Matanzas muestra un predominio de reacciones adversas frecuentes, moderadas y probables en mujeres con edades entre 60 a 69 años. Los antimicrobianos, los inhibidores de la enzima convertidora de angiotensina y los antiinflamatorios no esteroideos fueron los fármacos más notificados por los médicos y farmacéuticos produciendo síntomas a nivel del sistema digestivo y la piel.

Abstract Objective: To characterize suspected adverse drug reactions that occurred in older adults in Matanzas, from 2014 to 2019. Materials and methods: Pharmacovigilance (FV) case series study. The database of reports of suspected adverse drug reactions of the Provincial Pharmacovigilance Coordinating Unit, between 2014 and 2019, was reviewed. Results: A total of 1926 reports of adverse drug reactions in the elderly were evaluated, representing 24, 3% of the total. Women (56.7%) and the age group between 60 and 69 years (51.4%) predominated. Skin rash prevailed (13.4%). Antimicrobials and non-steroidal anti-inflammatory drugs were the ones most associated with ADRs in the skin, as well as in the digestive system. Cough was related to captopril. Adverse drug reactions of low frequency (55.2%), moderate (83.8%) and probable (77.1%) prevailed according to immutability. Conclusions: The safety profile in the elderly in the province of Matanzas shows a predominance of frequent, moderate and probable adverse reactions in women aged between 60 and 69 years. Antimicrobials, angiotensin-converting enzyme inhibitors and non- steroidal anti-inflammatory drugs were the drugs most reported by doctors and pharmacists, producing symptoms at the level of the digestive system and the skin.

Naltrexona em baixa dose (LDN): tendência de consumo nas capitais brasileiras e Distrito Federal, 2014-2020 / Low-dose naltrexone (LDN): consumption trend in Brazilian capitals and the Federal District, 2014-2020

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.

Política de medicamentos de alto costo en un hospital público pediátrico: Análisis de utilización y costos / High-cost medication policy at a public pediatric hospital: utilization and cost analysis

Objetivos. Analizar el circuito de utilización de los medicamentos de alto costo (MAC) y los resultados clínicos obtenidos en un hospital de pediatría público de alta complejidad de Argentina y presentar una estrategia de selección replicable para otras instituciones de similares características de la región. Métodos: Estudio prospectivo, descriptivo, aleatorizado, conducido en el Hospital de Pediatría Juan P. Garrahan de la Ciudad Autónoma de Buenos Aires en el período entre el 1 de setiembre de 2018 y el 31 de marzo de 2019. Se evaluaron dos unidades de estudio, la unidad paciente y la unidad MAC. Resultados: Los MAC consumen 7.921.200 dólares estadounidenses (USD) anuales y representan el 41% del costo de los medicamentos del hospital de alta complejidad. El 50% del costo de los MAC estuvo representado por la gammaglobulina (medicamento utilizado en diferentes enfermedades). Los pacientes proceden de toda la Argentina y otros países y un 44% tiene cobertura de salud. Los diagnósticos para los que se prescribieron MAC con mayor frecuencia fueron los relacionados con patología oncológica (leucemia linfoide aguda, leucemia mieloblástica aguda). El 54% de los pacientes presentó mejoría atribuible directamente a la administración de los MAC, 39% no presentó cambios y el 7% empeoró. Conclusiones: La efectividad en los resultados clínicos y el análisis de los circuitos de aprobación indican que, además de la aprobación por las entidades nacional e internacionales, la evaluación responsable por parte de las instituciones efectoras, mediante la discusión interdisciplinaria basada en la mejor evidencia, contribuye a optimizar la utilización de los MAC y la seguridad de los pacientes (AU)

Objectives. To analyze the utilization circuit of high-cost medications (HCM) and the clinical results obtained in a tertiarycare public pediatric hospital in Argentina and to present a selection strategy that may be disseminated to other institutions of similar characteristics in the region. Methods: A prospective, descriptive, randomized study was conducted at Hospital de Pediatría Juan P. Garrahan in Buenos Aires between September 1, 2018 and March 31, 2019. Two study units were evaluated, the patient and the HCM. Results: HCMs account for 7,921,200 US dollars (USD) per year and represent 41% of the cost of drugs in this tertiary-care hospital. Gamma globulin (a drug used for different diseases) accounted for 50% of the cost of HCMs. Patients came from Argentina and other countries and 44% had a health insurance. Cancer (acute lymphoid leukemia, acute myeloblastic leukemia) was the diagnosis for which HCMs were most frequently prescribed. Fifty-four percent of patients showed improvement directly attributable to the administration of HCMs, 39% showed no change, and 7% worsened. Conclusions: The effectiveness in clinical outcomes and the analysis of approval circuits show that, in addition to approval by national and international entities, responsible evaluation by the effector institutions through interdisciplinary discussion based on the best evidence contributes to optimizing the use of HCMs and patient safety (AU)

Fármacovigilancia de la carbamazepina en el Policlínico Marta Abreu. Santa Clara, 2022

Fundamento: en la práctica, el término estupefaciente se aplica a las especialidades farmacéuticas que contienen principios activos que actúan sobre el sistema nervioso central modificándolo y a las fórmulas magistrales con los mismos principios activos. Objetivo: caracterizar clínica y epidemiológicamente los pacientes que consumen carbamazepina en un área de salud del municipio de Santa Clara. Métodos: estudio descriptivo, transversal, en pacientes que consumen carbamazepina, pertenecientes al Policlínico Docente Marta Abreu, en el período del 1 de enero de 2021 al 1 de abril de 2022. Se incluyeron 209 pacientes y se midieron las siguientes variables: edad, sexo, número de pacientes según diagnósticos, número de pacientes según nuevos protocolos y tiempo de consumo del tratamiento. Resultados: predominó el grupo de edades de 51 a 60 con 43 pacientes (20,5 %), dentro de este grupo el sexo femenino (11,0 % del total); el diagnóstico predominante fue la epilepsia generalizada (93 pacientes). Predominó el sexo femenino, con 59 pacientes, y en ellas se encontró la mayor cantidad de expedientes vencidos, con un total de 16. Según nuevos protocolos, prevalecieron los pacientes con diagnóstico de neuralgia trigeminal, glosofaríngeo o facial (7 pacientes). En cuanto al tiempo de consumo predominaron los pacientes con igual diagnóstico a los anteriores y trastorno del comportamiento debido a enfermedad médica, ambos grupos con tratamientos de hasta tres años. Conclusiones: es importante el conocimiento sobre el uso y abuso de los estupefacientes así como mantener actualizado a todo el personal sanitario para lograr el óptimo control sobre estas sustancias.

Background: in practice, the term narcotic is applied to pharmaceutical specialties that contain active ingredients that act on the central nervous system, modifying it, and to master formulas with the same active ingredients. Objective: to characterize clinically and epidemiologically the patients who consume carbamazepine in a health area of the Santa Clara municipality. Methods: descriptive, cross-sectional study in patients consuming carbamazepine, belonging to the Marta Abreu Teaching Polyclinic, from January the 1st, 2021 to April the 1st, 2022. 209 patients were included and the following variables were measured: age, sex, number of patients according to diagnoses, number of patients according to new protocols and time of consumption of the treatment. Results: the age group from 51 to 60 predominated with 43 patients (20.5%), within this group the female sex (11.0% of the total); the predominant diagnosis was generalized epilepsy with a total of 93 patients. The female sex predominated with a total of 59 patients and in them the largest number of expired files was found, with a total of 16. According to new protocols, patients with a diagnosis of trigeminal, glossopharyngeal or facial neuralgia (7 patients) predominated. Regarding the time of consumption, patients with the same diagnosis as the previous ones and behavioral disorder due to a medical illness predominated, both groups with treatments of up to three years. Conclusions: knowledge about the use and abuse of narcotic drugs is important, as well as keeping all health personnel updated to achieve optimal control over these substances.

Eventos adversos sistémicos post-vacuna BCG. Serie de casos pediátricos / Systemic adverse events post-BCG vaccine. Pediatric case series

La vacuna BCG es clave para el control de la tuberculosis. En ocasiones se observan eventos adversos sistémicos causados por Mycobacterium bovis BCG; usualmente asociados a inmunodeficiencia. Describimos seis casos clínicos de niños vacunados con BCG al nacer, con complicaciones sistémicas post-vacunación. M{ETODO: Revisión de historias clínicas de pacientes con infección por M. bovis BCG atendidos en un hospital pediátrico, entre 2010 y 2019. RESULTADOS: De 400 casos confirmados de infecciones por complejo Mycobacterium tuberculosis; ocho fueron identificados como M. bovis BCG; seis casos correspondieron a eventos adversos sistémicos post-vacuna BCG: dos con lesiones cutáneas a distancia, dos osteomielitis y dos infecciones generalizadas. En cinco de los seis pacientes se detectó una alteración de la respuesta inmune. Un paciente falleció por falla multiorgánica, uno se derivó y cuatro completaron 12 meses de tratamiento: dos meses de isoniacida, rifampicina, etambutol, y moxifloxacina, y 10 meses de isoniacida y rifampicina. Tuvieron buena tolerancia a los medicamentos, sin recaída a los dos años. CONCLUSIÓN: La infección grave por M. bovis BCG es una rara complicación sistémica de la vacunación. Es razonable buscar defectos inmunológicos en los niños que desarrollan este tipo de eventos adversos.

The BCG vaccine is key to tuberculosis control. Systemic adverse events caused by Mycobacterium bovis BCG are occasionally observed; usually associated with immunodeficiency. In this report we describe six cases of children vaccinated with BCG at birth, with post-vaccination systemic complications. METHOD: retrospective review of medical records of patients with M. bovis BCG infection treated in a pediatric hospital between 2010 and 2019. RESULTS: Of 400 confirmed cases of Mycobacterium tuberculosis complex infection, eight identified as M. bovis BCG, six corresponded to systemic adverse events post-BCG vaccine: two distant skin lesions, two osteomyelitis and two generalized infections. An altered immune response was detected in five of the six patients. One patient died of multiorgan failure, one was referred and four completed 12 months of treatment: two months of isoniazid, rifampin, ethambutol, and moxifloxacin, and 10 months of isoniazid and rifampin. They had good tolerance to medications, without relapse at two years. CONCLUSION Serious M. bovis BCG infection is a rare systemic complication of vaccination. It is reasonable to look for immunological defects in children who develop these types of adverse events.

El largo y sinuoso camino de la farmacia clinica en Chile / The long and winding road of the clinical pharmacy in Chile

Clinical pharmacy is a health discipline in which pharmacists provide patient care that optimizes rational medication use and promotes health, wellness and disease prevention. The beginnings of clinical pharmacy in Chile were inspired by the origin in the School of Pharmacy of the University of California, San Francisco (UCSF), in the mid-1960s. However, the historical development in our country, both in teaching and in the professional field, was accompanied by difficulties and success, which became a long and winding road. This article shares the events that gave rise to its beginnings in Chile, first through teaching, then in pharmacovigilance and clinical pharmacokinetics, to later describe its professional expansion and recognition as a specialty of pharmacy. This article briefly recounts the history of the Chilean clinical pharmacy to this day. Some names of people or institutions were not mentioned. Therefore the authors apologize in advance to pharmacists and organizations whose contribution cannot be recognized in this way. However, we know that this specialty has not been forged only by the names that appear, but by all those who love and respect the work of the clinical pharmacy.

Caracterización de eventos adversos a hidroxicloroquina, ivermectina, azitromicina y tocilizumab en pacientes hospitalizados por COVID-19 en un hospital del Seguro Social de Salud del Perú / Characterization of adverse events to hydroxychloroquine, ivermectin, azithromycin and tocilizumab in patients hospitalized due to COVID-19 in a Peruvian Social Health Insurance hospital

Objetivos. Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta» en el tratamiento de pacientes hospitalizados por la COVID-19. Materiales y métodos. Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. Resultados. Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. Conclusiones. Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.

Objective. To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. Materials and Methods. We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. Results. We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. Conclusions. We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.

Bradycardia in a pediatric population after sugammadex administration: case series

Abstract Sugammadex is a distinctive neuromuscular reversal drug that acts by encapsulating the neuromuscular relaxant molecule and dislodging it from its site of action. Sugammadex has been approved for pediatric patients over 2 years of age. Although arrhythmias have been reported, there is no report of adverse effects in healthy children, such as severe bradycardia requiring intervention. We report two cases of severe bradycardia immediately after the administration of sugammadex in healthy children. Our aim is to alert to the occurrence of one of the most severe adverse effects of sugammadex, in the healthy pediatric population as well.

Analysis of reported adverse liver reactions associated with drugs used to treat patients with coronavirus disease 2019

Abstract Hepatic injury has been documented in patients with coronavirus disease 2019 (COVID-19). However, pharmacotherapy can frequently impact liver alterations, given the known hepatotoxic potential of drugs not effective to treat COVID-19. The objective of the present study was to evaluate reports of suspected liver reactions to drugs used for treating COVID-19, compare their use for other indications among patients with COVID-19, and assess possible interactions between them. We obtained reports on drugs used to treat COVID-19 (tocilizumab, remdesivir, hydroxychloroquine, and/or lopinavir/ritonavir), registered on June 30, 2020, from the Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard. We then analyzed the risk of developing liver events with these drugs by calculating the reported odds ratios (ROR). We identified 662, 744, and 1381 reports related to tocilizumab, lopinavir/ ritonavir, and hydroxychloroquine use, respectively. The RORs (95% confidence intervals) were 6.32 (5.28-7.56), 6.12 (5.22-7.17), and 9.07 (8.00-10.29), respectively, demonstrating an increased risk of liver events among patients with COVID-19 when compared with uninfected patients. The elevated risk of reporting adverse liver events in patients with COVID-19 who receive these drugs, alone or in combination, highlights the need for careful drug selection and efforts to reduce drug combinations without notable benefits. Similar to any other condition, the use of drugs without established efficacy should be avoided.

Utilidad estadística de los estudios de farmacovigilancia para evaluar reacciones adversas a medicamentos

Introducción: la detección oportuna y la evaluación de las reacciones adversas de los medicamentos es cada vez más importante. En Cuba existe la necesidad de profundizar y extender con alcance nacional los estudios de Farmacovigilancia, por tal motivo se expone como objetivo fundamentar sustentados en la estadística el uso de estudios de farmacovigilancia para la detección, registro, notificación y evaluación de las sospechas de las reacciones adversas de los medicamentos valorando su seguridad. Desarrollo: se brinda un resumen de tipos de estudios de farmacovigilancia con ejemplos de objetivos de investigaciones realizadas y publicadas en revistas científicas posibles a considerar y aplicar a las condiciones reales que tenga cada investigador, se presentan variables que ya han sido establecidas en otros estudios que se deben tener en cuenta para estudiar seguridad de los medicamentos y técnicas estadísticas teniendo en cuenta los tipos de variables a relacionar. Conclusiones: se concluye que resulta un logro científico conocer formas de profundizar y extender los estudios de Farmacovigilancia para tomar conocimiento de la seguridad de los fármacos y promover un uso racional, científico y adecuado de los mismos, en beneficio de la comunidad.

Introduction: timely detection and evaluation of adverse drug reactions is increasingly important. In Cuba there is a need to deepen and extend pharmacovigilance studies nationwide. That is why it is stated, based on statistics, the use of studies for the detection, registration, notification and evaluation of suspected adverse drug events, assessing their safety. Development: a summary of types of pharmacovigilance studies is provided with examples of objectives of research works already done and published in scientific magazines likely to consider and use in actual conditions each researcher has, and there are also presented variables that have already been established in other studies, which must be taken into account to study drug safety and statistical techniques considering the types of variables to be related. Conclusion: it is concluded that knowing ways to deepen and spread the Pharmacovigilance studies in order to be aware of drug safety and foster their rational, scientific and adequate use in the interests of the community is indeed a scientific accomplishment.

Introdução: a detecção e avaliação oportunas de reações adversas a medicamentos está se tornando cada vez mais importante. Em Cuba há uma necessida de de aprofundar e ampliar os estudos de farmacovigilância com âmbito nacional, por esta razão é declarado como um objetivo fundamentar com base em estatísticas o uso de estudos de farmacovigilância para a detecção, registro, notificação e avaliação de suspeitas de reações adversas de medicamentos que avaliam sua segurança. Desenvolvimento: um resumo dos tipos de estudos de farmacovigilância é fornecido com exemplos de objetivos de pesquisa realizados e publicados em possíveis revistas científicas a serem consideradas e aplicadas às condições reais que cada pesquisador possui, variáveis que já foram estabelecidas em outros estudos que devem ser levadas em conta para estudar a segurança de medicamentos e técnicas estatísticas levando em conta os tipos de variáveis a serem relacionadas. Conclusões: conclui-se que é uma conquista científica conhecer formas de aprofundar e ampliar os estudos de farmacovigilância para tomar conhecimento da segurança dos medicamentos e promover um uso racional, científico e adequado dos mesmos, em benefício da comunidade.

Short-term adverse effects of COVID-19 vaccines after the first, second, and booster doses: a cross-sectional survey from Punjab, Pakistan, and the implications

ABSTRACT Background: Safety and efficacy concerns regarding coronavirus disease 2019 (COVID-19) vaccines are common among the public and have a negative impact on their uptake. We aimed to report the adverse effects currently associated with the vaccine in Pakistan to build confidence among the population for its adoption. Methods: A cross-sectional study was conducted in five districts of the Punjab province of Pakistan between January and March 2022. The participants were recruited using convenience sampling. All data were analyzed using SPSS 22. Results: We recruited 1622 people with the majority aged between 25-45 years. Of these, 51% were female, including 27 pregnant women and 42 lactating mothers. Most participants had received the Sinopharm (62.6%) or Sinovac (17.8%) vaccines. The incidences of at least one side effect after the first (N = 1622), second (N = 1484), and booster doses (N = 219) of the COVID-19 vaccine were 16.5%, 20.1%, and 32%, respectively. Inflammation/erythema at the injection site, pain at the injection site, fever, and bone/muscle pain were common side effects of vaccination. No significant differences were observed in the adverse effect scores between all demographic variables except for pregnancy (P = 0.012) after the initial dose. No significant association was observed between any variable and the side effect scores of the second and booster doses of the vaccine. Conclusions: Our study showed a 16-32% prevalence of self-reported side effects after the first, second, and booster COVID-19 vaccinations. Most adverse effects were mild and transient, indicating the safety of different COVID-19 vaccines.

Atualização dos rastreadores para detecção de eventos adversos a medicamentos em pacientes hematológicos / Update of triggers for detection of adverse drug events in hematologic patients / Actualización de los rastreadores para detectar eventos farmacológicos adversos en pacientes hematológicos

Resumo: A utilização de rastreadores para a busca ativa e detecção de eventos adversos a medicamentos (EAM) tem ganhado espaço nos serviços de farmacovigilância. Assim, o objetivo principal do estudo foi propor uma nova lista de rastreadores para ser empregada em um centro especializado em hematologia do Rio de Janeiro, Brasil. A atualização da lista de rastreadores consistiu na revisão da lista atual, com a exclusão e inclusão de rastreadores. Para verificar o desempenho da nova lista de rastreadores, realizou-se um estudo transversal em que os novos rastreadores foram utilizados para investigar a ocorrência de EAM em pacientes atendidos na emergência ou hospitalizados no período de janeiro a março de 2022. Para cada suspeita de EAM identificada, caracterizaram-se o perfil do paciente e as reações adversas a medicamentos (RAM) quanto à causalidade e gravidade. O desempenho dos rastreadores e sua capacidade de captação de EAM foram calculados por meio dos indicadores: frequência do rastreador por 100 prontuários, frequência de EAM por 100 prontuários e valor preditivo positivo (VPP). Para avaliar o desempenho global da nova lista proposta, calculou-se o VPP. Foram identificadas 374 prescrições de rastreadores em 186 prontuários. Os mais eficientes na detecção de possíveis EAM foram: lidocaína, loperamida, bisacodil, filgrastim e clister de glicerina. O VPP global da nova lista sugerida foi 48% contra 10% da lista anterior. Este estudo demonstrou a importância de uma lista de rastreadores atualizada para o monitoramento dos EAM e o aprimoramento da assistência prestada.

Abstract: The use of triggers for the active search and detection of adverse drug events (ADEs) has been gaining ground within pharmacovigilance services. Thus, the main objective of the study was to propose a new list of triggers to be used in a center specialized in hematology in Rio de Janeiro, Brazil. The update of the list of triggers consisted of revising the current list, with the exclusion and inclusion of new triggers. To verify the performance of the new list of triggers, a cross-sectional study was conducted in which the new triggers were used to investigate the occurrence of ADEs in patients attended in the emergency unit or hospitalized from January to March 2022. For each suspected ADEs, the patient's profile and adverse drug reactions (ADRs) were characterized regarding causality and severity. The performance of the triggers and their ability to capture ADEs were estimated using the following indicators: frequency of the trigger per 100 medical records, frequency of ADEs per 100 records, and positive predictive value (PPV). To evaluate the overall performance of the proposed new list, the PPV was estimated. A total of 374 prescriptions for triggers were identified in 186 medical records. The most efficient in the detection of possible ADEs were: lidocaine, loperamide, bisacodyl, filgrastim and glycerin clyster. The overall PPV of the new suggested list was 48% versus 10% of the previous list. This study demonstrated the importance of an updated list of triggers for the monitoring of ADEs and improvement of the care provided.

Resumen: El uso de rastreadores en la búsqueda y detección activa de eventos adversos de medicamentos (EAM) viene ganando espacio dentro de los servicios de farmacovigilancia. Por lo tanto, el objetivo principal de este estudio fue proponer una nueva lista de rastreadores que se utilizarán en un centro de hematología especializado en Río de Janeiro, Brasil. La actualización de la lista de rastreadores consistió en la revisión de la lista actual, con la exclusión e inclusión de rastreadores. Para verificar el desempeño de la nueva lista de rastreadores, se realizó un estudio transversal en el que se utilizaron los nuevos rastreadores para investigar la aparición de EAM en pacientes atendidos en urgencias u hospitalizados en el periodo de enero a marzo de 2022. Para cada sospecha de EAM identificados, el perfil del paciente y las reacciones adversas a medicamentos (RAM) se caracterizaron por su causalidad y gravedad. El desempeño de los rastreadores y su capacidad para capturar EAM se calcularon mediante los indicadores: frecuencia del rastreador por cada 100 registros médicos, frecuencia de EAM por cada 100 registros médicos y valor predictivo positivo (VPP). Para evaluar el desempeño general de la nueva lista propuesta, se calculó el VPP. Se identificaron 374 recetas de rastreadores en 186 registros médicos. Los más eficientes en la detección de posibles EAM fueron lidocaína, loperamida, bisacodilo, filgrastim y enema de glicerina. El VPP general de la nueva lista sugerida fue del 48% frente al 10% de la lista anterior. Este estudio demostró la importancia de una lista actualizada de rastreadores para monitorear EAM y mejorar la atención brindada.

Análise de eventos adversos a medicamentos provenientes do sistema on-line brasileiro e o impacto global da pandemia da COVID-19 nas notificações / Analysis of adverse drug events from the Brazilian online system and the global impact of the COVID-19 pandemic on notifications

Justificativa: Os eventos adversos a medicamentos são uma das principais causas de mortes evitáveis nos sistemas de assistência à saúde e este problema se tornou ainda mais desafiador durante a pandemia da COVID-19, devido à falta de evidências robustas acerca de medicamentos efetivos para o tratamento da doença. Ademais, uma das principais barreiras para a compreensão aprofundada deste fenômeno é a problemática da subnotificação, especialmente em países de baixa e média renda. Objetivos: Analisar o perfil e a ocorrência de eventos adversos a medicamentos notificados por profissionais da saúde, pacientes e empresas/fabricantes no sistema nacional de informação on-line (NOTIVISA) nas cinco regiões brasileiras e avaliar o impacto da pandemia de COVID-19 nas notificações de eventos adversos a medicamentos às autoridades sanitárias em âmbito global. Método: Para o alcance dos objetivos propostos, foram realizados dois estudos. O primeiro estudo consistiu em um estudo epidemiológico e foram analisadas as notificações de eventos adversos a medicamentos inseridos no banco de dados do sistema brasileiro NOTIVISA, no período de 18 março de 2014 a 04 de dezembro de 2018, por duas pesquisadoras de forma independente. Procedeu-se à análise descritiva das variáveis desfecho e preditoras de eventos adversos a medicamentos, características dos pacientes, região brasileira, grau do dano e classificação do erro de medicação. O segundo estudo envolveu revisão sistemática da literatura conduzida nas bases de dados eletrônicas: Medline, Embase, Cinahl, Scielo e literatura cinzenta, utilizando os Descritores em Ciências da Saúde (DECs) e Medical Subject Heading (MeSH). A revisão foi relatada de acordo com as diretrizes PRISMA-2020 e a seleção dos estudos, bem como a extração de dados, foram realizadas por três revisores independentes. O risco de viés foi verificado por meio da ferramenta ROBINS-I. Resultados: Um total de 6.289 notificações foram analisadas e foi verificado um crescente aumento em seu número até o ano de 2016; posteriormente, queda gradual das notificações de eventos adversos a medicamentos foi detectada no período de 2017 e 2018. Houve maior frequência de notificações na região sudeste (48%) e os casos envolveram, predominantemente, pessoas do sexo feminino (52,1%), na faixa etária dos 18 a 65 anos (56,8%) e com neoplasias (22,9%). Além disso, 96% ocorreram durante a prestação de cuidados por um profissional, mais de 78% transcorreram no período diurno e 43% resultaram em danos leves. Na revisão sistemática, foram rastreados 6.014 artigos; destes, 1.863 duplicatas foram removidas. Após triagem, 4.143 foram excluídos por não atenderem aos critérios de inclusão e oito estudos foram elegíveis para a análise qualitativa. Não foram encontradas publicações na literatura cinzenta que contemplassem os critérios de inclusão propostos para esta revisão. Os estudos contemplam notificações de eventos adversos a medicamentos oriundas de 13 países, envolveram pacientes com idade média de 55 anos e sem comorbidades. Cinco estudos evidenciam que o número de notificações aumentou durante a pandemia contraponto outras duas publicações que apontam maior número de notificações antes da pandemia. Ademais, em um estudo, o resultado foi inconclusivo. Em dois estudos, foi identificado alto risco de viés. Conclusão: Os resultados do estudo demonstram que as notificações de EAM aumentaram durante a pandemia. No período pré-pandêmico houve destaque para a região sudeste conhecida com umas mais desenvolvidas, levando a danos leves principalmente vinculados ao erro de administração do medicamento comprometendo a segurança do paciente. Se faz necessário o reforço da importância no monitoramento e da real descoberta do motivo ao qual levou ao aumento nas notificações durante o período pandêmico a fim de melhorias nos processos de saúde e capacitação profissional para obter zero danos evitáveis.

Justification: Adverse drug events are one of the leading causes of preventable deaths in health care systems and this problem has become even more challenging during the pandemic of COVID-19, due to the lack of robust evidence about effective drugs for treating the disease. Moreover, one of the main barriers to a thorough understanding of this phenomenon is the problem of underreporting, especially in low- and middle-income countries. Objectives: To analyze the profile and occurrence of adverse drug events reported by health professionals, patients, and companies/manufacturers in the national online notification system (NOTIVISA) in the five Brazilian regions and to evaluate the impact of the COVID-19 pandemic on adverse drug events notifications to health authorities globally. Method: To achieve the proposed objectives, two studies were carried out. The first study consisted of an epidemiological study and the notifications of adverse drug events entered in the database of the Brazilian NOTIVISA system from March 18, 2014, to December 04, 2018, were analyzed. Only cases involving adverse drug events were screened and this process was carried out by two researchers independently. We performed a descriptive analysis of the outcome and predictor variables of adverse drug events, patient characteristics, Brazilian region, degree of harm, and medication error classification. The second study involved a systematic literature review conducted in the electronic databases: Medline, Embase, Cinalh, Scielo and grey literature, using Health Sciences Descriptors (HSC) and Medical Subject Heading (MeSH). The review was reported according to PRISMA-2020 guidelines and the selection of studies as well as data extraction were performed by three independent reviewers. The risk of bias was checked using the ROBINS-I tool. Results: A total of 6.289 notifications were analyzed and an increasing increase in their number was verified until the year 2016, subsequently, gradual decrease in adverse drug events notifications was detected in the period of 2017 and 2018. There was a higher frequency of notifications in the southeast region (48%) and the cases predominantly involved females (52.1%), in the age group 18 to 65 years (56.8%) and with neoplasms (22.9%). In addition, 96% occurred during the provision of care by a professional, more than 78% occurred during daytime hours, and 43% resulted in minor injuries. In the systematic review, 6,014 articles were screened; of these, 1,863 duplicates were removed. After screening, 4,143 were excluded for not meeting the inclusion criteria and eight studies were eligible for qualitative analysis. No publications were found in the gray literature that met the inclusion criteria proposed for this review. The studies contemplate notifications of adverse drug events from 13 countries, involved patients with a mean age of 55 years and without comorbidities. Five studies show that the number of notifications increased during the pandemic, as opposed to two other publications that indicate a higher number of notifications before the pandemic. Moreover, in one study, the result was inconclusive. In two studies, a high risk of bias was identified. Conclusion: The results of the study show that ADE notifications increased during the pandemic. In the pre-pandemic period, there was an emphasis on the southeastern region known as the most developed, leading to mild damage mainly linked to drug administration error, compromising patient safety. It is necessary to reinforce the importance of monitoring and the real discovery of the reason that led to the increase in notifications during the pandemic period in order to improve health processes and professional training to obtain zero preventable damage.

Análise de eventos adversos a medicamentos provenientes do sistema on-line brasileiro e o impacto global da pandemia da COVID-19 nas notificações / Analysis of adverse drug events from the Brazilian online system and the global impact of the COVID-19 pandemic on notifications

Justificativa: Os eventos adversos a medicamentos são uma das principais causas de mortes evitáveis nos sistemas de assistência à saúde e este problema se tornou ainda mais desafiador durante a pandemia da COVID-19, devido à falta de evidências robustas acerca de medicamentos efetivos para o tratamento da doença. Ademais, uma das principais barreiras para a compreensão aprofundada deste fenômeno é a problemática da subnotificação, especialmente em países de baixa e média renda. Objetivos: Analisar o perfil e a ocorrência de eventos adversos a medicamentos notificados por profissionais da saúde, pacientes e empresas/fabricantes no sistema nacional de informação on-line (NOTIVISA) nas cinco regiões brasileiras e avaliar o impacto da pandemia de COVID-19 nas notificações de eventos adversos a medicamentos às autoridades sanitárias em âmbito global. Método: Para o alcance dos objetivos propostos, foram realizados dois estudos. O primeiro estudo consistiu em um estudo epidemiológico e foram analisadas as notificações de eventos adversos a medicamentos inseridos no banco de dados do sistema brasileiro NOTIVISA, no período de 18 março de 2014 a 04 de dezembro de 2018, por duas pesquisadoras de forma independente. Procedeu-se à análise descritiva das variáveis desfecho e preditoras de eventos adversos a medicamentos, características dos pacientes, região brasileira, grau do dano e classificação do erro de medicação. O segundo estudo envolveu revisão sistemática da literatura conduzida nas bases de dados eletrônicas: Medline, Embase, Cinahl, Scielo e literatura cinzenta, utilizando os Descritores em Ciências da Saúde (DECs) e Medical Subject Heading (MeSH). A revisão foi relatada de acordo com as diretrizes PRISMA-2020 e a seleção dos estudos, bem como a extração de dados, foram realizadas por três revisores independentes. O risco de viés foi verificado por meio da ferramenta ROBINS-I. Resultados: Um total de 6.289 notificações foram analisadas e foi verificado um crescente aumento em seu número até o ano de 2016; posteriormente, queda gradual das notificações de eventos adversos a medicamentos foi detectada no período de 2017 e 2018. Houve maior frequência de notificações na região sudeste (48%) e os casos envolveram, predominantemente, pessoas do sexo feminino (52,1%), na faixa etária dos 18 a 65 anos (56,8%) e com neoplasias (22,9%). Além disso, 96% ocorreram durante a prestação de cuidados por um profissional, mais de 78% transcorreram no período diurno e 43% resultaram em danos leves. Na revisão sistemática, foram rastreados 6.014 artigos; destes, 1.863 duplicatas foram removidas. Após triagem, 4.143 foram excluídos por não atenderem aos critérios de inclusão e oito estudos foram elegíveis para a análise qualitativa. Não foram encontradas publicações na literatura cinzenta que contemplassem os critérios de inclusão propostos para esta revisão. Os estudos contemplam notificações de eventos adversos a medicamentos oriundas de 13 países, envolveram pacientes com idade média de 55 anos e sem comorbidades. Cinco estudos evidenciam que o número de notificações aumentou durante a pandemia contraponto outras duas publicações que apontam maior número de notificações antes da pandemia. Ademais, em um estudo, o resultado foi inconclusivo. Em dois estudos, foi identificado alto risco de viés. Conclusão: Os resultados do estudo demonstram que as notificações de EAM aumentaram durante a pandemia. No período pré-pandêmico houve destaque para a região sudeste conhecida com umas mais desenvolvidas, levando a danos leves principalmente vinculados ao erro de administração do medicamento comprometendo a segurança do paciente. Se faz necessário o reforço da importância no monitoramento e da real descoberta do motivo ao qual levou ao aumento nas notificações durante o período pandêmico a fim de melhorias nos processos de saúde e capacitação profissional para obter zero danos evitáveis.

Justification: Adverse drug events are one of the leading causes of preventable deaths in health care systems and this problem has become even more challenging during the pandemic of COVID-19, due to the lack of robust evidence about effective drugs for treating the disease. Moreover, one of the main barriers to a thorough understanding of this phenomenon is the problem of underreporting, especially in low- and middle-income countries. Objectives: To analyze the profile and occurrence of adverse drug events reported by health professionals, patients, and companies/manufacturers in the national online notification system (NOTIVISA) in the five Brazilian regions and to evaluate the impact of the COVID-19 pandemic on adverse drug events notifications to health authorities globally. Method: To achieve the proposed objectives, two studies were carried out. The first study consisted of an epidemiological study and the notifications of adverse drug events entered in the database of the Brazilian NOTIVISA system from March 18, 2014, to December 04, 2018, were analyzed. Only cases involving adverse drug events were screened and this process was carried out by two researchers independently. We performed a descriptive analysis of the outcome and predictor variables of adverse drug events, patient characteristics, Brazilian region, degree of harm, and medication error classification. The second study involved a systematic literature review conducted in the electronic databases: Medline, Embase, Cinalh, Scielo and grey literature, using Health Sciences Descriptors (HSC) and Medical Subject Heading (MeSH). The review was reported according to PRISMA-2020 guidelines and the selection of studies as well as data extraction were performed by three independent reviewers. The risk of bias was checked using the ROBINS-I tool. Results: A total of 6.289 notifications were analyzed and an increasing increase in their number was verified until the year 2016, subsequently, gradual decrease in adverse drug events notifications was detected in the period of 2017 and 2018. There was a higher frequency of notifications in the southeast region (48%) and the cases predominantly involved females (52.1%), in the age group 18 to 65 years (56.8%) and with neoplasms (22.9%). In addition, 96% occurred during the provision of care by a professional, more than 78% occurred during daytime hours, and 43% resulted in minor injuries. In the systematic review, 6,014 articles were screened; of these, 1,863 duplicates were removed. After screening, 4,143 were excluded for not meeting the inclusion criteria and eight studies were eligible for qualitative analysis. No publications were found in the gray literature that met the inclusion criteria proposed for this review. The studies contemplate notifications of adverse drug events from 13 countries, involved patients with a mean age of 55 years and without comorbidities. Five studies show that the number of notifications increased during the pandemic, as opposed to two other publications that indicate a higher number of notifications before the pandemic. Moreover, in one study, the result was inconclusive. In two studies, a high risk of bias was identified. Conclusion: The results of the study show that ADE notifications increased during the pandemic. In the pre-pandemic period, there was an emphasis on the southeastern region known as the most developed, leading to mild damage mainly linked to drug administration error, compromising patient safety. It is necessary to reinforce the importance of monitoring and the real discovery of the reason that led to the increase in notifications during the pandemic period in order to improve health processes and professional training to obtain zero preventable damage.

Sistema de monitoramento de biossimilares: desenvolvimento e avaliação de protótipo / Biosimilar monitoring system: prototype development and evaluation

A evolução da biotecnologia somada à ascensão da tecnologia para recombinação do DNA impulsionou a produção de biológicos ao longo de décadas. Com o término das patentes, os biossimilares emergiram com potencial de gerar um grande impacto na acessibilidade e assim estabelecer seu lugar no mercado após comprovação da equivalência com o medicamento biológico. Entretanto, as preocupações sobre as trocas de medicamentos biológicos e biossimilares é um importante debate atual que ressalta a relevância de acompanhamento pós mercado das pessoas em uso de biofármacos. Este estudo teve como objetivo elaborar um protótipo para identificar e validar os dados necessários para a construção de um software específico para o monitoramento dos medicamentos biossimilares para doenças inflamatórias imunomediadas, tendo em vista o processo de trabalho dos profissionais de saúde e da indústria farmacêutica, considerando os aspectos legais e legislativos das agências reguladoras em benefício do doente crônico. Trata-se de uma pesquisa aplicada, com abordagem qualitativa, na modalidade pesquisa-ação. A população amostral foi constituída por profissionais de saúde, profissionais da indústria farmacêutica, agência reguladora, usuários de medicamento biológico e medicamento biossimilar e especialistas de informática que aceitaram participar da pesquisa por meio da assinatura do Termo de Consentimento Livre e Esclarecido. Abordados na primeira etapa do estudo, os apontamentos dos integrantes do Comitê de Especialistas agregaram as diretrizes estabelecidas pelas agências reguladoras e contribuíram com o levantamento de requisitos que, permeado por padrões de terminologia, direcionou o desenvolvimento dos protótipos (estático e de software). O Adobe Illustrator® foi o editor de imagens vetoriais utilizado para desenvolver o protótipo estático e contribuir para consolidar as telas, ao passo que o protótipo de software explorou as potencialidades da tecnologia Angular e favoreceu a interação do usuário com as telas desenvolvidas. Na segunda fase do estudo, os integrantes do Comitê de Avaliadores acessaram o protótipo para avaliação da tecnologia por meio da aplicação de um questionário. Os resultados evidenciam a importância de desenvolver estratégias para identificar os desvios de qualidade e dessa forma minimizar os eventuais danos das novas gerações de medicamentos. Soma-se a relevância de identificar as trocas de medicamentos biológicos e biossimilares e qualificar as informações para favorecer o acompanhamento pós mercado dos biofármacos e, assim, fortalecer a farmacovigilância e contribuir com a segurança do paciente. A aproximação entre o pesquisador e as pessoas implicadas na jornada do paciente em uso de medicamento biológico e biossimilar proporcionou a inserção de perspectivas não previstas pela literatura e, sobretudo, delineou potenciais soluções para os problemas apontados.

The evolution of biotechnology added to the rise of technology for DNA recombination boosted the production of biologicals for decades. With the end of patents, biosimilars emerged with the potential to generate a great impact on accessibility and thus establish their place in the market after proof of equivalence with biological medicine. However, concerns regarding the exchange of biological and biosimilar medicines is an important current debate that highlights the relevance of post-market monitoring of people using biopharmaceuticals. This study aimed to develop a prototype to validate the data necessary for the monitoring of biological and biosimilar medicines for immune-mediated inflammatory diseases. It is an applied research, with a qualitative approach, in the action-research modality. The sample population consisted of health professionals, professionals from the pharmaceutical industry, regulatory agency, users of biological and biosimilar products and IT specialists who agreed to participate in the research by signing the Free and Informed Consent Form. Approached in the first stage of the study, the notes of the members of the Committee of Experts added the guidelines established by the regulatory agencies and contributed to the survey of requirements that, permeated by terminology standards, guided the development of prototypes (static and software). Adobe Illustrator® was the vector image editor used to develop the static prototype and contributed to consolidate the developed screens, while the software prototype explored the potential of Angular technology and favored user interaction with the screens developed. In the second phase of the study, the members of the Committee of Evaluators accessed the prototype for evaluating the technology through the application of a questionnaire. The results show the importance of developing strategies to identify quality deviations and minimize the potential damages of new generations of medicines. biopharmaceuticals and, thus, strengthen pharmacovigilance and contribute to patient safety. The approximation between the researcher and the people involved in the journey of the patient using biological and biosimilar medicines provided the insertion of perspectives not foreseen in the literature and, above all, outlining potential solutions to the problems mentioned.