A fiscalização sanitária de medicamentos na sociedade de risco / Drug health surveillance in the risk society

Resumo A fiscalização sanitária busca proteger a saúde da população impedindo que medicamentos fora do padrão, falsificados ou não registrados sejam consumidos e causem danos à saúde. Este ensaio objetiva contribuir para o debate acerca da fiscalização sanitária de medicamentos, num contexto de exposição contínua dos indivíduos a riscos que interferem no processo saúde-doença. Baseado nas reflexões sobre o risco sanitário e a sociedade de risco, associado à filosofia da vida de Canguilhem e à ergologia de Schwartz, discorre sobre a necessidade de se compreender a atividade humana e o trabalho para agir sobre o risco. Foram identificados possíveis desafios para a ação da fiscalização sanitária: (1) revisão conceitual; (2) atualização normativa; (3) desenvolvimento de mecanismos e ferramentas regulatórias; e (4) ampliação da capacidade técnica - formativa. Para enfrentá-los, considera-se um caminho promissor o envolvimento e a participação dos diversos atores nos espaços de cooperação e colaboração, bem como a construção de fórum permanente de debates ou de câmeras técnicas/setoriais. Estudos que dão visibilidade ao trabalho concreto das equipes de fiscalização sanitária e que analisam a atividade humana na relação entre o prescrito e o real podem ajudar a compreender a experiência de lidar com o risco, a adequação das normas, as necessidades de formação, entre outros.

Abstract Drug health surveillance protects the health of the population by preventing substandard, falsified, or unregistered drugs from being consumed and causing harm. This essay discusses drug health surveillance in a context of continuous exposure of individuals to risks that directly interfere with the health-disease process. Based on reflections about health risk and risk society, associated with Canguilhem's philosophy of life and Schwartz's ergology, it argues for the need to understand human activity and work to act on risk. Possible challenges for health inspection action include: (1) conceptual review; (2) regulatory updating; (3) development of regulatory mechanisms and tools; and (4) expansion of technical and training capacity. To face them, the involvement and participation of the various actors in cooperation and collaboration spaces, as well as the construction of a permanent forum of discussion or technical/sectorial meetings, is considered promising. Studies that highlight the concrete work of supervision teams and that analyze human activity in the relationship between the prescribed and the real can help to understand the experience of dealing with risk, the adequacy of standards, training needs, among others.

Analysis and health risk assessment, including recommendation of limits for heavy metals and harmful elements in Chinese patent medicines / 药学学报

Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.

Notificaciones espontáneas de sospechas de reacciones adversas a los medicamentos. Instituto Pedro Kourí / Spontaneous reporting of suspected drug adverse reactions in "Pedro Kouri" Institute of Tropical Medicine

Introducción: las reacciones adversas a los medicamentos se relacionan con la seguridad de los productos farmacéuticos. Están asociadas con altas tasas de morbilidad y mortalidad y alta carga económica para la sociedad. En el Instituto Pedro Kourí las notificaciones de reacciones adversas son inestables y no cuentan con un análisis general de los reportes. Objetivo: caracterizar las reacciones adversas a los medicamentos notificadas en el Instituto Pedro Kourí durante el periodo 2011 a 2013. Método: estudio de farmacovigilancia, observacional, descriptivo y transversal, a partir de todos los reportes de reacciones adversas notificados por los profesionales del Instituto durante el período de tiempo seleccionado. Se clasificaron según la imputabilidad, la frecuencia y el tipo de reacción. Fueron identificados los fármacos sospechosos y se estudiaron los pacientes que las manifestaron. Resultados: se reportaron 77 reacciones adversas, relacionadas todas con medicamentos antinfecciosos, de ellos los antirretrovirales con el 75,3 por ciento fue el grupo farmacológico que más se asoció con la producción de las mismas. La mayoría de los reportes se corresponden con pacientes masculinos (80,5 por ciento) y jóvenes (51,9 por ciento). Clasificaron como probables el 66,0 por ciento y definitivas el 6,4 por ciento. Conclusiones: todas las reacciones adversas a los medicamentos reportadas en el Instituto durante el trienio 2011-2013 se presentaron en pacientes con VIH/SIDA y se destacó la severidad de las mismas(AU)

Introduction: Adverse drug reactions are related to safety of pharmaceuticals, to high morbidity and mortality rates and to high economic burden upon the society. In Pedro Kouri Institute of Tropical Medicine, the adverse drug reaction notifications are inconsistent and there is no general analysis of reports. Objectives: To characterize the adverse drug reactions reported in Pedro Kouri Institute in the period of 2011 through 2013. Method: Observational, descriptive and cross-sectional pharmacovigilance study based on all the reports on adverse drug reactions by the professionals of the Institute during the selected period of time. They were classified according to attributable cause, frequency and type of reaction. Suspected drugs were identified and the patients who manifested these reactions were also studied. Results: Seventy seven adverse reactions were reported and all of them were related to anti-infection drugs; antiretrovirals accounted for 75.3 percent and was the drug group mostly associated to them. The majority of reports were made on males (80,5 percent) and young people (51,9 percent). They were classified as probable in 66 percent of cases and definitive in 6,4 percent. Conclusions: All the adverse drug reactions reported in the Institute in the 2011 to 2013 period were observed in HIV/aids patients and were severe ones(AU)

Discussion of quality control of chinese patent medicine with animal ingredients based on national post-market drug surveillance / 中国药学杂志

OBJECTIVE: To discuss quality control of Chinese patent medicine with animal ingredients, providing reference for standards improvement, quality supervision and regulated production. METHODS: Statutory standards and exploratory studies of Chinese patent medicines with animal ingredients tested in national post market surveillance between 2010 and 2014 were summarized. And technologies and methods developed for specific drugs were analyzed from the perspectives of safety, authenticity, effectiveness and controllability. RESULTS: Use of HPLC and GC is becoming more mature. Traditional microscopic and TLC methods can play a positive role in identification of animal drugs without index component. Mass spectrometry has been successfully applied in quality control of Chinese patent medicine with animal ingredients. CONCLUSION: National post market surveillance can provide comprehensive and elaborate evaluation on drug quality and can reveal potential risks. It's a powerful measure to promote quality of animal medicine.

Characterization of Potentized (Homeopathic, Anthroposophical and Antihomotoxic) Medicines Registered and Notified In Brazil

Potentized medicines include, according to the Brazilian legislation, homeopathic, anthroposophic, and antihomotoxic medicine and are regulated by the Brazilian Health Surveillance Agency (ANVISA). Aim: This study aims to analyze and describe a profile of potentized medicines manufactured in Brazil, either registered or notified. Methodology: Information was obtained by data analysis related to ANVISA’s electronic medicine registration system. Results: The results, obtained as of September 2012, showed that 106 potentized medicines were registered and 519 were notified. Among the registered medicines, 92.0% were combined and 100.0% of the notified were simple medicines. For registered medicines, there were equivalent manufacturing scales among them, whereas for notified medicines, there was a predominance of centesimal scales. Active pharmaceutical ingredients (API’s) of vegetal origin were the most commonly used for potentized medicine manufacturing processes; the oral route was the most common form of administration. Potentized medicines manufacturing units are more often located in southeast region of Brazil. In addition, homeopathic medicines prevail as registered or notified medicines, followed by anthroposophic medicines. Conclusions: The results of the study are expected to be useful as reference material for ANVISA to improve its regulatory activity as well the industry sector and other stakeholders...

Azitromicina y efectos cardiovasculares notificados al Sistema Cubano de Farmacovigilancia, 2003-2012 / Azithromycin and cardiovascular effects reported to ther Cuban System of Drug Surveillance in the period of 2003 through 2012

Introducción: la azitromicina, es un antibacteriano macrólido semisintético, al cual se han asociado efectos cardiovasculares, como la prolongación del intervalo QT y trastornos del ritmo que pueden ser fatales. La FDA alertó sobre un pequeño aumento de la mortalidad y riesgo de muerte en personas tratadas durante 5 días con este antibacteriano, y en el Centro Internacional de Monitoreo de Uppsala también se han registrado casos. Objetivo: caracterizar las reacciones adversas cardiovasculares a la azitromicina informadas a la Unidad Nacional Coordinadora de Farmacovigilancia durante el periodo 2003-2012. Métodos: estudio observacional, descriptivo y transversal utilizando la base de datos nacional de farmacovigilancia y las notificaciones espontáneas de reacciones adversas. Se trabajó con el universo de pacientes con reacciones adversas a la azitromicina. Las reacciones cardiovasculares se clasificaron según tipo de reacción, severidad, imputabilidad y frecuencia. Se estudiaron los pacientes que presentaron reacciones adversas según sexo y edad. RESULTADOS: se recibieron 1 960 notificaciones de reacciones adversas a la azitromicina en el periodo de estudio, de las cuales 96 se correspondieron con reacciones adversas cardiovasculares para el 4,9 por ciento. Predominaron en el sexo femenino (55,2 por ciento) y en los adultos (75 por ciento). Las palpitaciones representaron el 44,8 por ciento (43 pacientes), seguidas de la taquicardia y el dolor torácico. El 67,7 por ciento resultaron moderadas, el 71,9 por ciento probables y el 60,4 por ciento ocasionales. El 31,3 por ciento de las reacciones se pudo haber evitado y el motivo que predominó fue la indicación inadecuada en el 70 por ciento. CONCLUSIONES: aunque no se informan reacciones adversas cardiovasculares con desenlace fatal en personas tratadas con azitromicina, la tercera parte de ellas se podrían haber evitado; por lo se recomienda realizar una vigilancia más proactiva a este medicamento, así como informar todas las reacciones al Sistema Cubano de Farmacovigilancia(AU)

INTRODUCTION: azithromycin is a semisynthetic antimicrobial macrolide which is said to be associated with cardiovascular effects such as the prolongation of QT interval and disorders of the heart rate that may be fatal. The Food and Drug Administration has warned about a slight rise of mortality and risk of death in people treated for 5 days with this antibacterial drug; the International Center of Monitoring in Uppsala has also registered some cases.OBJECTIVE: to characterize the adverse cardiovascular reactions to azithromycin reported to the National Coordinating Unit of Drug Surveillance from 2003 through 2012. METHODS: observational, descriptive and cross-sectional study based on the national drug surveillance database and on the voluntary notifications of adverse reactions. The study universe was the patients with adverse reactions to azithromycin. The cardiovascular reactions were classified by type of reaction, severity, imputability and frequency. The patients presenting with adverse reactions were studied according to their sex and age. RESULTS: one thousand and nine hundred sixty adverse reactions to azithromycin were reported in the study period; 96 of them were cardiovascular reactions for 4.9 percent of the total amount. They were predominant in females (55.2 percent) and in adults (75 percent). Palpitations accounted for 44. 8 percent (43 patients) followed by tachycardia and chest pain. They were moderate in 67.7 percent of cases, probable in 71.9 percent and occasional in 60.4 percent. Regarding reaction, 31.3 percent of them could have been prevented and the predominant reason was the inadequate prescription of the drug in 70 percent of cases. CONCLUSIONS: although no adverse cardiovascular reactions causing death have been reported in individuals treated with azithromycin, one third of them could have been prevented, therefore it is recommended to perform more proactive surveillance on this drug and all types of reactions should be duly reported to the Cuban drug surveillance system(AU)

Reacciones adversas graves y mortales a los antimicrobianos: Sistema Cubano de Farmacovigilancia, 2003-2012 / Severe and deadly adverse reactions to antimicrobials: The Cuban drug surveillance system, 2003-2012

Introducción: las reacciones adversas a los antimicrobianos ocasionan más de 142 000 visitas a las salas de urgencias hospitalarias por año en los Estados Unidos. En Cuba han ocupado el primer lugar en el reporte, por ejemplo, en el año 2008 representaron el 31,4 por ciento del total de las reacciones adversas graves y el 25 por ciento de las reacciones adversas mortales. Objetivo: caracterizar las reacciones adversas graves y mortales a los antimicrobianos notificadas a la Unidad Nacional Coordinadora de Farmacovigilancia, durante el periodo 2003-2012. Métodos: se realizó un estudio de farmacovigilancia, observacional, descriptivo y transversal, utilizando la base de datos nacional de farmacovigilancia durante el periodo 2003-2012. Se trabajó con el total de reportes de reacciones adversas graves y mortales a los antimicrobianos. Las reacciones adversas se clasificaron según tipo de reacción, sistema de órgano afectado, imputabilidad y frecuencia. Se identificaron los principales antimicrobianos sospechosos y se estudiaron los pacientes que presentaron reacciones adversas según sexo y edad. Resultados: se detectaron 631 sospechas de reacciones adversas graves y mortales a los antimicrobianos, de ellas fueron 550 graves y 81 mortales. Predominaron el sexo femenino con 60,1 por ciento y 405 adultos. Las reacciones adversas comprometieron los sistemas: general 30,4 por ciento, respiratorio 25,2 por ciento y cardiovascular 14,9 por ciento. El shock anafiláctico fue la reacción más reportada y la penicilina el fármaco más relacionado con esta. El 73,5 por ciento fueron probables y el 58,9 por ciento ocasionales. Conclusiones: las reacciones adversas graves y mortales predominaron en el sexo femenino y en los adultos. La penicilina fue el fármaco más relacionado. Las reacciones adversas probables y ocasionales fueron la mayoría en el estudio...

Introduction: adverse reactions to antimicrobials cause over 142 000 visits to emergency rooms yearly in the United States of America. They held the first place in the report, for example in 2008 when they accounted for 31.4 percent of all the severe adverse reactions and 25 percent of deadly adverse reactions. Objective: to characterize the severe and deadly adverse reactions to antimicrobials reported to the National Coordinating Unit of Drug Surveillance in the 2003-2012 period. Methods: a cross-sectional, descriptive and observational study of drug surveillance was conducted by using the national drug surveillance database in the 2003-2012 period. The total number of reports of severe and deadly adverse reactions to antimicrobials was considered. The adverse reactions were classified by type of reaction, affected organ system, attribution and frequency. The main suspected antimicrobials were identified whereas the patients who presented adverse reactions were studied by sex and age. Results: six hundred and thirty one suspected severe and deadly adverse reactions to antimicrobials were detected, 550 of them were severe and 81 deadly. Females predominated for 405 adults 60.1percent. The adverse reactions compromised the general system 30.4 percent, the respiratory system 25.2 percent and the cardiovascular one 14.9 percent. Anaphylactic shock was the most reported reaction and penicillin was the most associated to it. In the study, 73.5 percent of reactions were probable and 58.9 percent were occasional. Conclusions: severe and deadly adverse reactions prevailed in females and in adults. Penicillin was the most associated factor whereas the probable and occasional adverse reactions were the majority in the study...

Eventos adversos observados años después del tratamiento con factor de transferencia / Adverse events occurred some years after the application of a transfer factor treatment

Introducción: el factor de transferencia es un inmunoestimulante que se emplea en varias enfermedades, su seguridad en las condiciones de la práctica médica no se ha establecido. Objetivos: identificar eventos adversos presentados años después de finalizado el tratamiento con factor de transferencia y determinar la relación entre su utilización y los eventos observados. Métodos: estudio observacional, retrospectivo, de fármacovigilancia activa. El universo estuvo constituido por 413 pacientes tratados con este fármaco entre los años 2001 y 2004 en 11 hospitales de La Habana. El periodo de observación abarcó los 6 a 8 años posteriores al tratamiento. Los pacientes fueron entrevistados acerca de la presencia de infecciones, cáncer y otros eventos, en su hogar. Si un evento era la muerte, se entrevistaba al familiar para registrar causa y fecha. Resultados: se entrevistaron 356 pacientes, 66 (18,53 por ciento) presentaron al menos un evento adverso, 21(31,8 por ciento) en mayores de 60 años. Se registraron 87 eventos adversos, 8 (9,2 por ciento) fueron infecciones como hepatitis B, hepatitis C, foliculosis, mononucleosis y verrugas vulgares, 1 (1,1 por ciento) cáncer y 78 (89,7 por ciento) otros eventos. Su relación con la administración del fármaco resultó condicional en 64 (73,6 por ciento) pacientes e improbable en 21 (24,1 por ciento), en esta última categoría se incluyeron las infecciones y la mayoría de los eventos mortales. Conclusiones: los eventos adversos que se registraron en los pacientes, años después de haber recibido tratamiento con factor de transferencia, no se consideran relacionados con su administración, aunque necesitan ser vigilados pues la información obtenida en este estudio debe ser contrastada con un mayor número de observaciones y estudios observacionales controlados

Introduction: the transfer factor is an immunostimulant that is used to treat several diseases but its safety in the medical practice has not been assured yet. Objectives: to identify the adverse events occurred some years after the end of a transfer factor treatment and to determine the association of the use and the observed events. Methods: observational active drug surveillance study. The universe of study was 413 patients who were treated with the transfer factor from 2001 to 2004 in eleven hospitals located in La Habana province. The observation period ranged 6 to 8 years after the treatment. The patients were interviewed at home on the occurrence of infections, cancer or any other events. If some death occurred, then a family member was interviewed to record the cause and the date of the decease. Results: three hundred fifty six patients were interviewed; 66(18.53 percent) stated at least one adverse event and 21(31.80 percent) events occurred in over 60 years-old patients. Eighty seven adverse effects were recorded; 8 (9.20 percent) comprised infections such as hepatitis B, hepatitis C, foliculosis, mononucleosis and warts, one (1.10 percent) event corresponded to cancer and 78 (89.70 percent) to other type of events. Their relationship with the administration of the drug was considered as conditional in 64 events (73.60 percent) and as unlikely in 21 (24.10 percent) events comprising infections and most of the fatal events. Conclusions: the adverse events observed in the patients, some years after the end of the treatment with the transfer factor, were not considered to be related to the administration of this drug; however, they must be under surveillance since the information obtained from this study should be compared with the information collected by a higher number of observations and of controlled observational studies

Eventos adversos observados después del tratamiento con factor de transferencia / Adverse events after treatment with the transfer factor

Introducción: el factor de transferencia es un inmunoestimulante que se emplea en una amplia gama de enfermedades. Su eficacia y seguridad han sido evaluadas en ensayos clínicos prerregistro, pero se conoce poco sobre su seguridad en condiciones de la práctica habitual, de ahí la necesidad de vigilar su uso y contribuir a establecer su relación beneficio/riesgo. Objetivos: identificar eventos adversos en pacientes tratados con factor de transferencia, determinar grado de asociación fármaco-evento observado y su gravedad. Métodos: estudio observacional, descriptivo, prospectivo y multicéntrico de farmacovigilancia activa. Se observó durante el año siguiente al término del tratamiento con factor de transferencia, a una serie de 282 pacientes tratados por su médico de asistencia entre abril de 2001 y abril de 2002, en 9 hospitales en La Habana. Se analizaron los eventos adversos presentados, su gravedad, si existía asociación con el fármaco, la cantidad de eventos por paciente, la dosis administrada y la edad del paciente. Resultados: el 13,8 por ciento de los pacientes observados tuvo al menos un evento adverso, de ellos 38,5 por ciento tenía entre 45-59 años. Los esquemas de tratamiento con dosis altas y prolongadas no provocaron más eventos que los ya encontrados. Se identificaron 80 eventos adversos, 55 por ciento leves y en 80 por ciento se consideró improbable su relación con el medicamento. Ninguno se clasificó definitivo o probable, mientras que eventos como fiebre, artralgia, disnea, mialgia, alergia y astenia, se consideraron reacciones adversas posibles y leves. Conclusiones: la mayoría de los eventos adversos presentados, durante el año siguiente de finalizado el tratamiento con factor de transferencia, fueron leves y no relacionados con su uso. Aun así, los productores del medicamento deberían advertir a profesionales y pacientes sobre las reacciones adversas posibles detectadas

Introduction: the transfer factor is an immunologic stimulant used in a wide range of diseases. Its safety and efficiency have been evaluated in pre-registration clinical trials, but little is known about its safety margin under regular practical conditions, hence the need of closely watching its use and setting the benefit-risk relation. Objectives: to identify adverse events in patients treated with the transfer factor and to determine the level of association of the drug and the observed adverse event and severity. Methods: prospective, multicentered, descriptive and observational study of active drug surveillance. Two hundred and eighty two patients, who were attended by their physicians from April 2001 to April 2002 in 9 hospitals of Havana, were observed for one year after the end of a treatment with the transfer factor. The occurrence of adverse events as well as their severity, association with the drug, the number of events per patient, the supplied dosage and the age of the patient was all analyzed. Results: in this group of patients, 13,8 percent had at least one adverse effect; 38,5 percent were aged 45 to 59 years. The treatment schemes with high and prolonged dosage did not cause any further event. Eighty adverse effects were identified, 55 percent mild and 80 percent were considered as unlikely related with the drug. None of them was definitive or probable whereas fever, arthralgia, dysnea, myalgia, allergy and asthenia were considered as possible mild adverse reactions. Conclusions: most of adverse events during the year after the end of treatment with the transfer factor were mild and unrelated to the use of the drug. However, the drug manufacturers should advise professionals and patients on the possible occurrence of adverse reactions

Diseño e implantación de un programa electrónico de farmacovigilancia con captura en línea en el Hospital Infantil de México Federico Gómez / Design and implementation of an electronic program of medical drugs surveillance with online capture in the Children Hospital of Mexico Federico Gomez

Introducción. Se describe el desarrollo de un Programa de Farmacovigilancia (PROFAVI) de captura electrónica en línea en el Hospital Infantil de México Federico Gómez (HIMFG), que incluye desde su diseño hasta su instalación, así como sus potencialidades y beneficios. Métodos. Se diseñó un Software en Acces y Visual Basic, apegado a la Norma Oficial Mexicana (NOM), que incluyó 5 etapas (diseño hasta liberación). Resultados. Se generaron 7 módulos de llenado: datos del paciente; reacción adversa; medicamento sospechoso; farmacoterapia concomitante; historia clínica; procedencia de la información y reportes estadísticos. Los requerimientos mínimos del software y hardware fueron: Explorer 5.0; Windows 98; espacio libre en disco de 5 GB; Acrobat Reader 5.0 y Excel 4.0; Pentium II + 500 Mhz; RAM 128 Mb; monitor de 1 024 x 768 píxeles y 16 bits. Conclusiones. Ventajas del PROFAVI: brindar mayor confiabilidad en la información y disminución del tiempo de captura; responder a los requerimientos de la NOM, incluyendo datos anexos; establecer un Centro de Referencia, ubicado en el HIMFG, para los Institutos Nacionales de Salud, Hospitales Federales y Estatales; ser un elemento de apoyo para la investigación y la educación; e incrementar la cultura del reporte en México, entre otros.

Introduction. The development of a program of medical drug surveillance (PROFAVI) with online electronic capture in the Children Hospital of Mexico Federico Gomez (HIMFG) is described. It includes from its design up to the implementation as well as its potencialities and benefits. Methods. A computer program was designed in Acces and Visual Basic, according to the Oficial Mexican Regulation (NOM), it included 5 stages (from design to liberation). Results. Seven modules of data capture were made for: patient data, adverse reaction; suspected medication; other medication; clinical history; source of the information and statistical reports. Software and hardware requirements were: Explorer 5.0; Windows 98; free disc space de 5 GB; Acrobat Reader 5.0 and Excel 4.0; Pentium II + 500 Mhz; RAM 128 Mb; 1 024 x 768 píxeles y 16 bits monitor. Conclusions. Advantages of PROFAVI: provide more reliability to the information and reduce capturing time; fullfill the NOM's requirements, including attached data; establish a reference center at HIMFG, for the National Institutes of Health, State and Federal Hospitals; serve as a support element for research and education; increase the reporting culture in Mexico among other effects.