Estudo das potenciais interações medicamentosas (PIM) associadas às alterações da concentração plasmática, eficácia e toxicidade, do imatinibe, dasatinibe e nilotinibe.
Data
2022-02-08
Autores
Oliveira, Camila Helena Gabacci de 
Orientadores
Silva, Antonio Távora de Albuquerque
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A Leucemia Mielóide Crônica (LMC) é uma doença mieloproliferativa clonal, estando diretamente associada à presença do cromossomo Filadélfia (Ph), que é detectado em mais de 90% dos pacientes com LMC e que também é caracterizada por leucocitose com desvio à esquerda e esplenomegalia. Os inibidores de tirosina-quinase (ITK) representam um marco importante no tratamento de pacientes com LMC, pois melhorou a sobrevida da maioria dos pacientes, onde o Imatinibe, o Nilotinibe e o Dasatinibe, são exemplos de ITK. Pelo exposto e entendendo a importância do uso adequado e racional dos ITK no tratamento da LMC, este trabalho teve por objetivo, identificar e descrever as Potenciais Interações Medicamentosas (PIM) do Imatinibe, Nilotinibe e Dasatinibe, relacionadas às alterações das respectivas concentrações plasmáticas, à redução do efeito terapêutico (ou eficácia) e à toxicidade desses medicamentos. Trata-se de um estudo que utilizou como fontes de informação de PIM, o IBM Micromedex® DRUGDEX® e UpToDate®. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de São Paulo (CEP Nº 4.088.310.320). Este estudo identificou nas duas bases supracitadas que, para os três ITK (imatinibe, nilotinibe e dasatinibe) ocorre maior número de PIM relacionada a diminuição da concentração plasmática, exceto para o Imatinibe, na base Micromedex®, onde foi observado o mesmo quantitativo das PIM de interesse relacionadas à diminuição e ao aumento da concentração plasmática. Com relação a variável de PIM relacionada a redução da eficácia, foram identificadas PIM com essa característica na base Micromedex® apenas para o Nilotinibe e na base UpToDate®, para Imatinibe e Nilotinibe. Quanto a variável de PIM relacionada à Toxicidade, foram identificadas PIM com essa característica para os 3 ITK supracitados, em ambas as bases (Micromedex® e UpToDate®).Este estudo também verificou que os Mecanismos de PIM mais frequentes foram: 1) Indução do metabolismo do ITK, por CYP3A4; 2) Inibição do metabolismo do ITK, por CYP3A4; e 3) Inibição do ácido gástrico. Com este trabalho, foi possível concluir que é importante a utilização de várias bases de dados para o estudo de PIM uma vez que foram detectadas diferenças entre as Bases de dados deste estudo. Além disso, a manifestação clínica de PIM deste trabalho, em alguns casos, pode ocasionar falha terapêutica do tratamento com os ITK acima citados, ou ainda, levar a casos de toxicidade, mostrando a importância do estudo de PIM bem como do seguimento e monitoramento dos pacientes em uso desses ITK, no acompanhamento da farmacoterapia.
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease and is directly associated with the presence of the Philadelphia (Ph) chromosome, which is detected in more than 90% of CML patients and is also characterized by leukocytosis with left shift and splenomegaly. Tyrosine-kinase inhibitors (TKIs) represent an important milestone in the treatment of patients with CML, as it has improved the survival of most patients, where Imatinib, Nilotinib, and Dasatinib, are examples of TKIs. Given the above and understanding the importance of the appropriate and rational use of TKIs in the treatment of CML, this study aimed to identify and describe the Potential Drug Interactions (PIM) of Imatinib, Nilotinib, and Dasatinib, related to changes in their plasma concentrations, reduction of therapeutic effect (or efficacy) and toxicity of these drugs. This is a study that used IBM Micromedex® DRUGDEX® and UpToDate® as PIM information sources. This study was approved by the Research Ethics Committee of the Universidade Federal de São Paulo (CEP No. 4.088.310.320). This study identified in the two aforementioned databases that for the three TKIs (Imatinib, Nilotinib, and Dasatinib) there was a greater number of PIM related to decreased plasma concentration, except for Imatinib, in the Micromedex® database, where the same quantity of PIM of interest related to decreased and increased plasma concentration was observed. Regarding the PIM variable related to reduced efficacy, PIM with this characteristic was identified in the Micromedex® database only for Nilotinib and in the UpToDate® database, for Imatinib and Nilotinib. This study also verified that the most frequent mechanisms of PIM were: 1) Induction of TKI metabolism by CYP3A4; 2) Inhibition of TKI metabolism by CYP3A4, and 3) Gastric acid inhibition. With this study, it was possible to conclude that it is important to use several databases for the study of PIM since differences were detected among the databases of this research. Furthermore, the clinical manifestation of PIM in this study, in some cases, can cause the therapeutic failure of treatment with the above-mentioned TKIs, or even lead to cases of toxicity, showing the importance of the study of PIM as well as the follow-up and monitoring of patients using these TKIs, in the follow-up of pharmacotherapy.
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease and is directly associated with the presence of the Philadelphia (Ph) chromosome, which is detected in more than 90% of CML patients and is also characterized by leukocytosis with left shift and splenomegaly. Tyrosine-kinase inhibitors (TKIs) represent an important milestone in the treatment of patients with CML, as it has improved the survival of most patients, where Imatinib, Nilotinib, and Dasatinib, are examples of TKIs. Given the above and understanding the importance of the appropriate and rational use of TKIs in the treatment of CML, this study aimed to identify and describe the Potential Drug Interactions (PIM) of Imatinib, Nilotinib, and Dasatinib, related to changes in their plasma concentrations, reduction of therapeutic effect (or efficacy) and toxicity of these drugs. This is a study that used IBM Micromedex® DRUGDEX® and UpToDate® as PIM information sources. This study was approved by the Research Ethics Committee of the Universidade Federal de São Paulo (CEP No. 4.088.310.320). This study identified in the two aforementioned databases that for the three TKIs (Imatinib, Nilotinib, and Dasatinib) there was a greater number of PIM related to decreased plasma concentration, except for Imatinib, in the Micromedex® database, where the same quantity of PIM of interest related to decreased and increased plasma concentration was observed. Regarding the PIM variable related to reduced efficacy, PIM with this characteristic was identified in the Micromedex® database only for Nilotinib and in the UpToDate® database, for Imatinib and Nilotinib. This study also verified that the most frequent mechanisms of PIM were: 1) Induction of TKI metabolism by CYP3A4; 2) Inhibition of TKI metabolism by CYP3A4, and 3) Gastric acid inhibition. With this study, it was possible to conclude that it is important to use several databases for the study of PIM since differences were detected among the databases of this research. Furthermore, the clinical manifestation of PIM in this study, in some cases, can cause the therapeutic failure of treatment with the above-mentioned TKIs, or even lead to cases of toxicity, showing the importance of the study of PIM as well as the follow-up and monitoring of patients using these TKIs, in the follow-up of pharmacotherapy.