Avaliação da qualidade farmacêutica de doses de medicamentos psicoativos: implicações na terapêutica medicamentosa
Data
2018-04-26
Autores
Eserian, Jaqueline Kalleian 
Orientadores
Galduroz, Jose Carlos Fernandes
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A prática de divisão de comprimidos e a utilização de medicamentos líquidos de uso oral administrados com o auxílio de acessórios (gotejadores, copos medida e seringas dosadoras) possibilitam a obtenção de uma grande variedade de doses individualizadas, sendo de grande utilidade para esquemas de ajuste de doses, componente essencial no gerenciamento de medicamentos psicoativos. Entretanto, questões relacionadas à eficácia e segurança da divisão de comprimidos têm sido discutidas com relação a desvios substanciais na quantidade de substância ativa entre as metades, ao mesmo tempo que a utilização de alguns medicamentos líquidos de uso oral tem sido investigada pelas vigilâncias sanitárias em relação à obtenção de doses apropriadas. Objetivo: Avaliar as características físico-químicas e determinar os efeitos da prática de divisão de comprimidos e utilização de medicamentos líquidos de uso oral contendo substâncias psicoativas na obtenção de doses preconizadas pela clínica. Metodologia: Utilizou-se como modelo de obtenção de doses individualizadas medicamentos de referência, genéricos e similares na forma de comprimidos com vinco (haloperidol), medicamentos líquidos de uso oral com apresentação em gotejador em PVC (haloperidol), gotejador em
vidro (clonazepam), copo medida (valproato de sódio) e seringa dosadora (carbamazepina). Foram avaliados o teor e uniformidade de conteúdo de doses para os comprimidos divididos tanto mecanicamente quanto não mecanicamente e para os medicamentos líquidos de uso oral. Para os comprimidos, avaliaram-se ainda as propriedades físicas, variação de peso e perda de massa. A quantificação dos medicamentos foi feita de acordo com métodos farmacopeicos. Resultados e discussão: Todos os acessórios avaliados apresentaram, em magnitude e extensão variadas, ao menos um fabricante com doses nas faixas de sub ou superdose. A maior variação na quantidade de substância ativa entre as doses foi observada para comprimidos divididos mecanicamente (60,7%). Houve variação na quantidade de substância ativa nas doses entre os fabricantes para a mesma quantidade de líquido dispensada em até 37,8% para o gotejador em PVC, 33,5% para o gotejador em vidro, 27,6% para o copo medida e 12,3% para a seringa dosadora. A qualidade do
produto e a quantidade de substância ativa dispensada por dose são essenciais tanto para a segurança e eficácia do tratamento com medicamentos psicoativos quanto para esquemas de ajuste de doses. Diferenças entre os fabricantes de um mesmo medicamento podem potencialmente comprometer uma eventual
substituição entre os mesmos durante o decorrer do tratamento. Conclusão: O risco inerente de administração de sub ou superdoses decorrente do fato de que parte dos acessórios e das metades de comprimidos avaliados não cumpriu a finalidade de
fornecer doses exatas e precisas, além da falta de padronização entre os fabricantes de um mesmo medicamento, acarreta em implicações clínicas iminentes associadas.
Introduction: Tablet splitting and liquid medications for oral use dosed with measuring devices (droppers, dosing cup and syringe) allow the delivery of a great range of individual doses useful for dose adjustment, which is essential in the management of psychoactive medications. However, efficacy and safety of tablet splitting have been discussed regarding substantial deviation in the active substance content between the halves, while some liquid medications for oral use have been investigated by the regulatory agencies regarding appropriate dose delivery. Objective: To evaluate physical-chemical characteristics and determine the effects of tablet splitting and utilization of liquids for oral use of medications containing psychoactive substances in clinical doses delivery. Methodology: Reference, generic and similar drugs of scored tablets (haloperidol), liquids for oral use measured with droppers in PVC packing (haloperidol), droppers in glass packing (clonazepam), dosing cups (sodium valproate) and syringes (carbamazepine) were adopted as models for individual doses delivery. Potency and drug content uniformity were evaluated for mechanically and non-mechanically split tablets and for liquid medications for oral use. Physical properties, weight variation and weight loss were also evaluated for the tablets. Quantification of active substances was determined according to pharmacopeial methods. Results and discussion: All devices presented, in different magnitude and range, at least one manufacturer delivering sub or super doses. The greatest variation in drug content between doses was observed for mechanically split tablets (60.7%). Doses varied between manufacturers for the same amount of dispensed liquid around 37.8% for droppers in PVC packing, 33.5% for droppers in glass packing, 27.6% for dosing cups and 12.3% for syringes. The quality of the product and the amount of active substance per dose in psychoactive medications are essential for treatment efficacy and safety as well as dose adjustment. Differences between manufacturers of the same medication potentially compromise an eventual substitution among them during the treatment. Conclusion: The inherent risk of administration of sub or super doses because part of the devices and tablet halves did not deliver accurate and precise doses besides the lack of uniformity between manufacturers of the same medication lead to imminent associated clinical implications.
Introduction: Tablet splitting and liquid medications for oral use dosed with measuring devices (droppers, dosing cup and syringe) allow the delivery of a great range of individual doses useful for dose adjustment, which is essential in the management of psychoactive medications. However, efficacy and safety of tablet splitting have been discussed regarding substantial deviation in the active substance content between the halves, while some liquid medications for oral use have been investigated by the regulatory agencies regarding appropriate dose delivery. Objective: To evaluate physical-chemical characteristics and determine the effects of tablet splitting and utilization of liquids for oral use of medications containing psychoactive substances in clinical doses delivery. Methodology: Reference, generic and similar drugs of scored tablets (haloperidol), liquids for oral use measured with droppers in PVC packing (haloperidol), droppers in glass packing (clonazepam), dosing cups (sodium valproate) and syringes (carbamazepine) were adopted as models for individual doses delivery. Potency and drug content uniformity were evaluated for mechanically and non-mechanically split tablets and for liquid medications for oral use. Physical properties, weight variation and weight loss were also evaluated for the tablets. Quantification of active substances was determined according to pharmacopeial methods. Results and discussion: All devices presented, in different magnitude and range, at least one manufacturer delivering sub or super doses. The greatest variation in drug content between doses was observed for mechanically split tablets (60.7%). Doses varied between manufacturers for the same amount of dispensed liquid around 37.8% for droppers in PVC packing, 33.5% for droppers in glass packing, 27.6% for dosing cups and 12.3% for syringes. The quality of the product and the amount of active substance per dose in psychoactive medications are essential for treatment efficacy and safety as well as dose adjustment. Differences between manufacturers of the same medication potentially compromise an eventual substitution among them during the treatment. Conclusion: The inherent risk of administration of sub or super doses because part of the devices and tablet halves did not deliver accurate and precise doses besides the lack of uniformity between manufacturers of the same medication lead to imminent associated clinical implications.
Descrição
Citação
ESERIAN, Jaqueline Kalleian. Avaliação da qualidade farmacêutica de doses de Medicamentos psicoativos: implicações na terapêutica medicamentosa. 2018. 101 f. Tese (Doutorado em Psicobiologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2018.