Análise do perfil das notificações de inefetividade de medicamentos recebidas pela Agência Nacional de Vigilância Sanitária por meio do sistema de notificações em vigilância sanitária (NOTIVISA), nos anos de 2016 e 2017

Abstract

Therapeutic ineffectiveness is a relevant adverse event in the context of pharmacovigilance. During the prescription or use of a drug, both the health professional and the patient consider that it will be effective. It is known, however, that drugs are not effective in all individuals, due to factors related to the patient or to the drug itself. Identifying the medicine ineffectiveness is in the scope of pharmacovigilance and, therefore, health surveillance. The aim of this study was to analyze the profile of therapeutic ineffectiveness reports received by the Brazilian Health Surveillance Agency (Anvisa), through the Health Surveillance Notification System (Notivisa), from 2016 to 2017. The study was approved by the Research Ethics Committee of UFC (University of Ceará, Brazil). The data was analyzed in the Notivisa through the filters “Medicine name” and “Adverse Event”. In order to identify reports of therapeutic ineffectiveness, the following terms were used: “insufficient anesthesia”, “decreased therapeutic response”, “pregnancy during oral contraceptive use”, “therapeutic ineffectiveness”, “unexpected therapeutic ineffectiveness”, “ineffectiveness”, “lack of effect”, “inhibitory drug interaction”, “drug interaction”, “ineffective drug”, “resistance”, “tachyphylaxis” and “tolerance”. MicroStrategy® software was used to extract information from Notivisa. The data presented by MicroStrategy® has been exported to Microsoft Office Excel® for the construction of charts and tables. The variables investigated were: origin of the notification (Brazilian State); profile of the notifying institution; categories of causality defined by the World Health Organization; terms most used by Notivisa reporters related to therapeutic ineffectiveness; active ingredient and medicine batch. In the analyzed period, 489 suspects of therapeutic ineffectiveness were reported by notifiers from São Paulo (130), Brasília (58), Goiás (58), Paraná (52), Ceará (34) and Rio de Janeiro (34). Hospitals sent 311 reports (63.6%) of the total received, with emphasis on sentinel hospitals, which sent 191 of these notifications. The adverse event “therapeutic ineffectiveness” occurred mainly in the states of São Paulo (164), Minas Gerais (67), Paraná (56), Ceará (35) and Rio de Janeiro (35). The notifiers consider that 74% of their suspicions of ineffectiveness refer to serious cases, a percentage of seriousness close to that found in the evaluation of Anvisa technicians (59.9%). The two main causal classifications attributed by the Anvisa´s evaluators were “possible” (61.7%) and “conditional / unclassifiable” (14.1%). The main terms used by the notifiers to report suspected ineffectiveness were “medicine ineffectiveness” (38.3%), “lack of effect” (28.1%) and “therapeutic ineffectiveness” (17.9%). The therapeutic group most reported was anesthetics (39.9%) – with emphasis on bupivacaine associated with other drugs (cited in 144 reports, 29.4% of total reports) – followed by antibiotics (13.3%) and oncological drugs (9.0%). None of the batches cited during the study period were subjected to sanitary measures by Anvisa. Despite its limitations, Notivisa is an important tool for the practice of pharmacovigilance. The difficulty to obtain measures of disproportionality –¬ such as odds ratio (ROR) and expected number of reports (e) ¬– from Notivisa reports, even with the use of MicroStrategy®, however, is a limiting factor, which may impair Anvisa's regulatory decisions.