ABSTRACT
While effective ways to prevent withdrawal symptoms from psychiatric drugs remain unclear, a highly accepted clinical approach for treatment discontinuation is to gradually reduce doses over time. The objective of this review is to gather the current strategies for tapering of psychiatric drugs described in the literature and guidelines in an attempt to identify the most promising one. Literature review and search for practice guidelines provided by government agencies and medical organizations were performed. Different strategies for tapering were found: linear tapering, hyperbolic tapering (by exponential dose reduction and pre-established dose-response curves), extended dosing, and substitution for a long half-life drug. The use of guidelines offers support for patients and prescribers, increasing the likelihood of achieving effective drug discontinuation. Nevertheless, the lack of standardization found among the guidelines makes any attempt to reduce or stop the drug very difficult for prescribers. Hyperbolic tapering by exponential dose reduction appears to be the most promising strategy for psychiatric drug discontinuation. Yet, we still face a constant challenge: how to safely obtain flexible doses for the discontinuation of drugs, particularly during the last steps in which lower doses are required. Further studies are needed to reduce the barriers associated with psychiatric drug discontinuation.
Subject(s)
Substance Withdrawal Syndrome , Humans , Remission InductionABSTRACT
Introdução: Os desvios da qualidade de medicamentos (DQM) apresentam grande relevância no âmbito da farmacovigilância, devendo ser investigados e monitorados, uma vez que podem levar a uma grande variedade de desfechos clínicos. Objetivo: Discutir sobre a caracterização dos DQM no âmbito da farmacovigilância por meio de uma revisão narrativa da literatura. Método: Foi realizada uma busca abrangente em bases de dados utilizando-se os descritores: "farmacovigilância", "queixas técnicas (QT)", "DQM" e "sistemas de notificação", incluindo estudos relacionados diretamente ao tema proposto, realizados no Brasil e publicados no período de 2005 a 2020. Resultados: Os DQM podem estar relacionados a alterações no próprio medicamento, ao conteúdo e integridade da embalagem e à rotulagem. Dos 18 estudos selecionados (14 artigos, dois capítulos de livro e duas dissertações) contendo notificações de DQM na forma de QT de medicamentos, dois avaliaram exclusivamente notificações de QT de medicamentos (100,0%), enquanto o restante apontou que estas representavam de 0,6% a 70,0% do total de notificações realizadas em estabelecimentos de saúde do país. Os principais DQM evidenciados foram alterações no aspecto do produto, ausência/redução na quantidade do medicamento e problemas nas embalagens. Conclusões: Considera-se que as notificações envolvendo DQM representem um excelente indicador de qualidade dos medicamentos disponíveis no mercado, vindo a contribuir na qualificação de fornecedores e distribuição de produtos conformes à população.
Introduction: Substandard drugs (SD) present great relevance in the area of pharmacovigilance and should be investigated and monitored as they can lead to several clinical outcomes. Objective: To discuss the characteristics of SD in the area of pharmacovigilance through a narrative review. Method: A comprehensive search was performed on databases using the descriptors "pharmacovigilance", "technical complaints (TC)", "SD" and "notification systems" including studies directly concerning the subject conducted in Brazil and published between 2005 and 2020. Results: SD issues might be associated with drug product alterations, content and integrity of the package and labeling. Among the 18 selected studies (14 articles, two book chapters and two dissertations) regarding SD notifications reported as drug TC, two exclusively evaluated drug TC notifications (100.0%), while the rest showed that this type of notification represented 0.6% to 70.0% of the total of notifications made in national health establishments. The main SD issues found were: alterations on the product aspect; absence/reduction in the amount of drug product; and, package problems. Conclusions: Notifications involving SD issues are considered an excellent quality indicator for the drugs available in the market, which contributes to suppliers' qualification and provision of consistent products for the population.
ABSTRACT
Introduction: Product switching followed by suspected adverse events are common and unsettling for antiepileptic drugs. The objective of this case study was to describe the investigation performed after report of suspected therapeutic failure in pediatric patients following a switch to a different valproate manufacturer and identify strategies concerning medication management for improving therapeutic outcomes. Case description: It was reported that different pediatric patients' condition changed (agitation/ seizures) after refilling the same drug prescription (sodium valproate syrup) from a different manufacturer. Medical staff reported a suspected therapeutic failure and some units of the product batch associated with the problem were seized by the local Post-marketing Surveillance Service for investigation of potential quality deviations. The seized units were evaluated by the State's Surveillance Laboratory, nevertheless, drug potency was found to be 98.7%. Conclusion: We consider that the reported event could be associated with aspects of medication use, i.e. potential dose measurement deviations resulting from remaining of residual liquid in the cup or eventual delay at prescription refilling process and consequential - even though brief - pharmacotherapy discontinuity. Patient education and counseling by pharmacists are essential for preventing drug-related problems and enhancing positive outcomes of pharmacotherapy.
ABSTRACT
Individualized dosing is often required in pharmacotherapy, particularly for pediatric and geriatric patients and adjustment of drugs that demand dose adaptation. This study aimed to evaluate critical quality attributes (CQAs) of doses obtained by distinct approaches for achieving individual dosing. Approaches were evaluated as follows: subdivision of tablets by splitter and hand (haloperidol) and delivery by plastic dropper bottle (haloperidol), glass dropper bottle (clonazepam), dosing cup (sodium valproate), and dosing syringe (carbamazepine), including brand name, generic, and similar marketed products. Measuring devices were packaged with their respective product. Drug content uniformity was assessed to each substance according to pharmacopeial methods. Tablets subdivided by splitter had the poorest performance among all approaches, in which doses ranged around 60% of the labeled amount (Acceptance Value = 58.1 and RSD = 23.2%). The greatest performances were observed for the dosing syringe which fulfilled all the requirements for dose precision and for the glass dropper bottle. There were significant differences in dose delivery between manufacturers of the same medicine when measuring the same volume or number of drops. High drug content variability is extremely harmful to pharmacotherapy and may result in therapeutic failure or toxicity. It is crucial that measuring devices and scoring of tablets be checked for functionality and standardized for different manufacturers of the same medicine. Part of the approaches for achieving individual dosing did not meet the quality needs for drug content and uniformity. Yet, our findings show that more accurate and precise dosing can be accessed when using the dosing syringe and glass dropper bottle.
Subject(s)
Anticonvulsants/administration & dosage , Anticonvulsants/standards , Dosage Forms/standards , Drug Delivery Systems/methods , Quality Control , Syringes/standards , Administration, Oral , Aged , Child , Dose-Response Relationship, Drug , Humans , TabletsABSTRACT
O medicamento é um produto farmacêutico com finalidade profilática, curativa ou para fins de diagnóstico. A forma farmacêutica está relacionada à via de administração. O objetivo deste trabalho foi avaliar a alteração do aspecto de medicamentos, provenientes de queixas técnicas e de programas de monitoramento da qualidade. No período de 2010 a 2014, 119 amostras coletadas pelos Serviços de Vigilância Sanitária foram analisadas quanto ao aspecto e as alterações foram confrontadas com as especificações técnicas dos medicamentos, sendo que 73,1% das amostras foram insatisfatórias. Apresentaram resultados insatisfatórios 82,0% das suspensões e 63,0% dos comprimidos, principalmente devido a alterações na suspensibilidade e na cor, respectivamente. Os desvios de qualidade constatados estavam relacionados à forma farmacêutica, independente da propriedade farmacológica. A principal consequência do uso de medicamentos com aspecto alterado é a não adesão ao tratamento e a interrupção de esquemas terapêuticos de doenças com metas de erradicação, como tuberculose e sífilis. Os resultados insatisfatórios contribuem no direcionamento de ações estratégicas de políticas públicas de medicamentos, na criação de modelos de intervenção preventiva, na regulação sanitária e na promoção do uso racional de medicamentos, desta maneira evitando riscos sanitários...
Subject(s)
Drug Contamination , Total Quality ManagementABSTRACT
OBJECTIVE: The objective of the present study was to assess whether the administration of polyunsaturated fatty acids (PUFAs) would lead to alterations in cocaine-conditioned place preference by correlating behavioral data and plasma levels of PUFAs. METHODS: Five groups of C57Bl/6J mice received a linseed oil supplement or a control solution for 19 days and were conditioned to cocaine. RESULTS: PUFAs did not exert a protective effect against cocaine-conditioned place-preference behavior, although there were significant differences in the levels of eicosapentaenoic acid (EPA) and linoleic acid among the groups tested. Higher doses of PUFAs might be necessary to induce a change in the plasma level of EPA in cocaine-conditioned mice. DISCUSSION: PUFAs had no effect on cocaine-conditioned place preference.
