Estratégias para gerenciamento de risco para a presença de nitrosaminas em medicamentos da classe “sartana”
Arquivos
Data
2022-12-20
Autores
Raymundo, Felipe de Souza 
Orientadores
Calixto, Leandro Augusto
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
As nitrosaminas são uma classe de compostos presente em diversos alimentos do cotidiano além de também estarem presentes na água, um componente essencial para a vida. O que muitos desconhecem ou não compreendem é o seu potencial como impureza mutagênica e potencial carcinógeno segundo o International Agency for Research on Cancer e a Organização Mundial da Saúde. Em 2018 a Agência Européia de Medicamentos identificou a presença dessas impurezas no medicamento Valsartana, um medicamento empregado no tratamento contra a hipertensão arterial. Após este incidente, houve outros relatos de outros medicamentos da classe “sartana”, e posteriormente de outras classes terapêuticas com precursores conhecidos ou suspeitos de conterem NDMA ou outras nitrosaminas carcinogênicas em seu processo de síntese, levando a um recall e retirada destes produtos dos mercados mundiais. O presente trabalho consiste em uma revisão bibliográfica com o objetivo de descrever o que são as nitrosaminas, sua formação e as consequências de ingestão imoderada, bem como apresentar um resumo dos métodos e equipamentos utilizados pelos laboratórios e farmacopeias para detecção e quantificação destes compostos, além de avaliar possíveis metodologias de qualidade de processos industriais de produção para elaborar uma metodologia de gerenciamento de risco adequada e apontar os limites aceitáveis destes compostos em medicamentos para evitar o recolhimento de produtos existentes no mercado, prevenir futuras reavaliações regulatórias além de prevenir incidentes de cânceres em pacientes que fazem uso das classes de medicamentos afetadas. Por fim pode ser concluído que a junção das ferramentas de processos industriais somadas a métodos farmacopeicos devidamente adequados e comprovados junto a limites bem estabelecidos constituem como uma porta inicial para mitigar o surgimento de novos casos.
Nitrosamines are a class of compounds present in many everyday foods and are also present in water, an essential component for life. What many do not know or understand is their potential as a mutagenic impurity and potential carcinogen according to the International Agency for Research on Cancer and the World Health Organization. In 2018 the European Medicines Agency identified the presence of these impurities in the drug Valsartana, a drug employed in the treatment against high blood pressure. Following this incident, there have been other reports of drugs in the "sartan" class, and later of other therapeutic classes with precursors known or suspected to contain NDMA or other carcinogenic nitrosamines in their synthesis process, leading to recall and withdrawal of these products from world markets. The present work consists of a literature review with the objective of describing what nitrosamines are, their formation, and the consequences of immoderate ingestion, as well as presenting a summary of the methods and equipment used by laboratories and pharmacopoeias for the detection and quantification of these compounds, in addition to evaluating possible industrial production processes of industrial processes to elaborate an adequate risk management methodology and review acceptable limits of these compounds in drugs to avoid the recall of existing products on the market, prevent future regulatory reevaluations, and prevent incidents of cancers in patients who use the affected drugs. Ultimately, it can be concluded that the combination of industrial process tools and adequate and proven pharmacopeial methods with well-established limits is a gateway to mitigate the emergence of new cases.
Nitrosamines are a class of compounds present in many everyday foods and are also present in water, an essential component for life. What many do not know or understand is their potential as a mutagenic impurity and potential carcinogen according to the International Agency for Research on Cancer and the World Health Organization. In 2018 the European Medicines Agency identified the presence of these impurities in the drug Valsartana, a drug employed in the treatment against high blood pressure. Following this incident, there have been other reports of drugs in the "sartan" class, and later of other therapeutic classes with precursors known or suspected to contain NDMA or other carcinogenic nitrosamines in their synthesis process, leading to recall and withdrawal of these products from world markets. The present work consists of a literature review with the objective of describing what nitrosamines are, their formation, and the consequences of immoderate ingestion, as well as presenting a summary of the methods and equipment used by laboratories and pharmacopoeias for the detection and quantification of these compounds, in addition to evaluating possible industrial production processes of industrial processes to elaborate an adequate risk management methodology and review acceptable limits of these compounds in drugs to avoid the recall of existing products on the market, prevent future regulatory reevaluations, and prevent incidents of cancers in patients who use the affected drugs. Ultimately, it can be concluded that the combination of industrial process tools and adequate and proven pharmacopeial methods with well-established limits is a gateway to mitigate the emergence of new cases.