Intravenous therapy device labeling in Intensive Care Units: an integrative review / Etiquetado de dispositivos de terapia intravenosa en Unidades de Cuidados Intensivos: revisión integradora / Rotulagem de dispositivos de terapia intravenosa em Unidades de Terapia Intensiva: revisão integrativa

ABSTRACT Objectives: to synthesize the evidence on intravenous device labeling used to identify medications administered to patients in Intensive Care Units, with a view to preventing medication errors. Methods: an integrative review, in the LILACS, IBECS, Embase, MEDLINE, Scopus, Web of Science and CINAHL databases, from November to December 2021, using descriptors and selection criteria. Data were collected in 11 articles and subsequently classified, summarized and aggregated. Results: pre-designed labels, with pre-defined colors and information, help to prevent medication identification errors. There is still a lack of standardization in the practice of labeling syringes, intravenous lines, infusion pumps and saline solution bags. There are errors related to the lack of labeling devices or to their performance with incomplete information. Conclusions: device labeling is a barrier to defending the medication system safety and should be standardized.

RESUMEN Objetivos: sintetizar las evidencias sobre el etiquetado de dispositivos intravenosos utilizados para identificar medicamentos administrados a pacientes en Unidades de Cuidados Intensivos, con el objetivo de prevenir errores de medicación. Métodos: revisión integradora, en las bases de datos LILACS, IBECS, Embase, MEDLINE, Scopus, Web of Science y CINAHL, de noviembre a diciembre de 2021, utilizando descriptores y criterios de selección. Los datos fueron recolectados en 11 artículos y posteriormente clasificados, resumidos y agregados. Resultados: etiquetas prediseñadas, con colores e información predefinidos, ayudan a prevenir errores de identificación de medicamentos. Todavía hay una falta de estandarización en la práctica de etiquetado de jeringas, líneas intravenosas, bombas de infusión y bolsas de suero. Hay errores relacionados con la falta de etiquetado de los dispositivos o con su realización con información incompleta. Conclusiones: el etiquetado de los dispositivos es una barrera para defender la seguridad del sistema de medicamentos y debe ser estandarizado.

RESUMO Objetivos: sintetizar as evidências sobre a rotulagem de dispositivos intravenosos utilizada para a identificação de medicamentos administrados nos pacientes em Unidades de Terapia Intensiva, com vistas à prevenção dos erros de medicação. Métodos: revisão integrativa, nas bases de dados LILACS, IBECS, Embase, MEDLINE, Scopus, Web of Science e CINAHL, no período de novembro-dezembro de 2021, com uso de descritores e emprego de critérios de seleção. Os dados foram coletados em 11 artigos e, posteriormente, classificados, sumarizados e agregados. Resultados: rótulos pré-desenhados, com cores e informações pré-definidas contribuem para prevenir os erros de identificação dos medicamentos. Persiste a falta de padronização da prática de rotulagem em seringas, linhas intravenosas, bomba infusoras e bolsas de soro. Há erros relacionados à ausência de rotulagem dos dispositivos ou à sua realização com informações incompletas. Conclusões: a rotulagem dos dispositivos é uma barreira para a defesa da segurança do sistema de medicação, devendo ser padronizada.

Bulas de medicamentos cardiovasculares: elas têm informações sobre precauções necessárias aos idosos? / Cardiovascular drug labeling: Do they have information on necessary precautions for older people?

OBJETIVO: Analisar a existência de informações, em bulas destinadas aos profissionais de saúde, sobre precaução de uso de medicamentos cardiovasculares em idosos. METODOLOGIA: Trata-se de estudo documental realizado por meio de análise de dados contidos em bulas de medicamentos. Analisou-se a existência, na bula, de informações sobre precauções no uso de medicamentos para idosos, conforme descrito no Consenso Brasileiro de Medicamentos Potencialmente Inapropriados para Idosos de 2016. RESULTADOS: Dos 29 medicamentos pertencentes ao grupo do sistema cardiovascular que devem ser evitados por idosos e estão disponíveis no Brasil, 15 independem da condição clínica prévia do paciente para que sejam vetados para os idosos. Desses 15, apenas 3 medicamentos (20%) têm informações explícitas concordantes com o Consenso (metildopa, digoxina e espironolactona); 2 (13,33%) têm informações explícitas ausentes; 4 (26,66%) têm informações explícitas discordantes; e 6 bulas (40%) foram categorizadas como informações não explícitas. Quanto às precauções dos medicamentos de acordo com a condição clínica do paciente, incluíram-se 14 medicamentos que devem ser evitados por idosos e estão disponíveis no Brasil. Destes, 12 (85,71%) têm em suas bulas recomendações concordantes com o Consenso, porém não explícitas, e 2 (14,28%) não têm as contraindicações. CONCLUSÕES: A maioria das bulas carece de informações sobre precauções de uso de medicamentos para a população idosa.

OBJECTIVE: To analyze the existence of information on drug labeling intended for health professionals on the precaution of cardiovascular drugs use in older people. METHODS: This is a documentary study, carried out with the analysis of data contained in drug labelings. The existence of information on precautions in the use of drugs for older people as described in the 2016 Brazilian Consensus on Potentially Inappropriate Drugs for Older People (Consenso Brasileiro de Medicamentos Potencialmente Inapropriados para Idosos de 2016). RESULTS: Of the 29 drugs belonging to the cardiovascular system group that should be avoided by older people and are available in Brazil, 15 are independent of the clinical condition. Of these fifteen, only three drugs (20%) have explicit information in accordance with the Consensus (methyldopa, digoxin, and spironolactone); two (13.33%) have missing explicit information; four (26.66%) have explicitly discordant information; and six drug labels (40%) were categorized as non-explicit information. Regarding drug precautions according to clinical condition, 14 drugs were included. Of these, 12 (85.71%) have equal contraindications of that of Consensus on their drug labels, however, non-explicit; and two (14.28%) contraindications are missing. CONCLUSION: Most drug labels lack information on the precautions for the use of drugs in older people.

Analysis of individual case safety reports of drug-induced anaphylaxis to the Korea Adverse Event Reporting System

PURPOSE: To identify causative agents of the drug-induced anaphylaxis (DIA) by using the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System (KIDS-KAERS) database (Ministry of Food and Drug Safety) in Korea and to check their labeling information regarding anaphylaxis.METHODS: Among Individual Case Safety Reports from January, 2008 to December 2017, cases of DIA were analyzed for demographics, causative agents and fatal cases resulting in death. The domestic drug labeling, Micromedex and U.S. Food and Drug Administration (FDA) drug package insert, were reviewed to check if the labeling information on suspected causative agents contains anaphylaxis.RESULTS: A total of 4,700 cases of DIA were analyzed. The mean age was 49.85±18.32 years, and 2,642 patients (56.2%) were females. Among 8,664 drugs reported as causative agents, antibiotics (27.4%) accounted for the largest portion. There were 18 fatal cases: antibiotics (7 cases), antineoplastic agents (4 cases) were the major causative drugs for the mortality cases. Of 513 drugs reported as suspected causative agents, 103 (20.1%) did not list anaphylaxis as an adverse effect on domestic drug labeling and 16 (3.1%) did not reflect anaphylaxis in any of 3 adverse drug information.CONCLUSION: Analysis of 10-year data showed that antibiotics were the main cause of DIA and the mortality rate was 0.7%. In 3.1% of suspected drugs, there was no description of anaphylaxis in any of the drug labeling.

Evaluation of color-coded drug labeling to identify endovenous medicines / Evaluación de los etiquetados con código de colores para la identificación de medicamentos endovenosos / Avaliação da rotulagem com código de cores para identificação de medicamentos endovenosos

ABSTRACT Objective: To analyze the opinion of nursing professionals on the design, practicality of use and the usefulness of color-coded drug labeling in a pediatric intensive care unit. Methods: A cross-sectional study with 42 nursing professionals. A structured questionnaire was used based on a five-level Likert scale. To assess the proportions, a binomial test was used. Results: Concordance ratio >0.8 for all propositions related to design, practicality and most of the propositions related to error prevention. Conclusion: According to the opinion of the nursing team, the implemented technology has an adequate design, as well as being practical and useful in the prevention of medication errors in the population at the ICU.

RESUMEN Objetivo: Analizar la opinión de los profesionales de Enfermería acerca del diseño, la practicidad del uso y la utilidad de los etiquetados con código de colores en una unidad de terapia intensiva pediátrica. Método: Estudio transversal, realizado con 42 profesionales de enfermería. Se utilizó un cuestionario estructurado basado en una escala Likert de cinco niveles. Para el análisis de las proporciones, se utilizó la prueba binomial. Resultados: Se encontró la proporción de concordancia >0,8 para todas las proposiciones relacionadas con el diseño, la practicidad del uso y la mayoría de las proposiciones relacionadas con la prevención de errores. Conclusión: Según la opinión del equipo de enfermería frente al objeto de estudio, la tecnología implementada tiene un diseño adecuado, además de ser práctica y útil en la prevención de errores de medicamentos en población atendida en la UTI.

RESUMO Objetivo: Analisar a opinião dos profissionais de enfermagem sobre o design, a praticidade do uso e a utilidade da rotulagem com código de cores em uma unidade de terapia intensiva pediátrica. Método: Estudo transversal, realizado com 42 profissionais de enfermagem. Utilizou-se um questionário estruturado com base em uma escala Likert de cinco níveis. Para a análise das proporções, utilizou-se o teste binomial. Resultados: Houve proporção de concordância >0,8 para todas as proposições relacionadas ao design, à praticidade do uso e à maioria das proposições relacionadas à prevenção de erros. Conclusão: De acordo com a opinião da equipe de enfermagem, frente ao objeto de estudo, a tecnologia implementada tem design adequado, além de ser prática e útil na prevenção de erros de medicamentos em população atendida na UTI.

Herramientas para identificar los riesgos de diseño de las competencias para las comercializadoras de medicamentos / Tools to identify the risks the design of the competencies for the marketers of medications

RESUMEN Fundamento: la gestión por competencias en las organizaciones adquiere un carácter estructural vinculado a resultados, enmarcados en diferentes procesos, lo que constituye una alternativa para la mejora del rendimiento de los recursos humanos de las empresas de medicamentos que aspiran alcanzar servicios de excelencia. Objetivo: diseñar herramientas para identificar los riesgos en el diseño de las competencias de los recursos humanos que laboran en empresas de medicamentos. Desarrollo: se realizó un estudio por un grupo de expertos en recursos humanos, que partió de las valoraciones de las estrategias, objetivos, valores, misiones y políticas que deben manifestarse en la implementación de la gestión por competencias, se aplicaron técnicas como la tormenta de ideas, entrevistas a directivos de la empresa de medicamentos, método de experto y el análisis modal de fallos y sus efectos, se obtuvo el diseño de un algoritmo para la detención de fallos en el proceso de identificación de las competencias y los instrumentos para el análisis cualitativo y cuantitativo de los fallos de diseños. Conclusiones: es de gran significación el diseño de las herramientas para la detección y la reducción de los riesgos en el diseño de los perfiles de competencias.

ABSTRACT Background: management by competencies in organizations acquires a structural character linked to results, framed in different processes, which constitutes an alternative for improving the performance of human resources of drug companies that aspire to achieve excellent services. Objective: to design tools to identify the risks in the design of the competences of the human resources that work in medicine companies. Development: a study was carried out by a group of experts in human resources, which started from the valuations of the strategies, objectives, values, missions and policies that should be manifested in the implementation of the management by competencies, techniques such as the storm of ideas, interviews with executives of the drug company, expert method and the modal analysis of failures and their effects, the design of an algorithm was obtained for the arrest of failures in the process of identification of the competences and the instruments for the analysis qualitative and quantitative design failures. Conclusions: the design of tools for the detection and reduction of risks in the design of competency profiles is of great significance.

Quando a cor ajuda / When color helps

RESUMO Objetivo: Reduzir a identificação errônea de colírios, por meio do uso de substâncias com cores diferentes. Métodos: Um grupo de 34 voluntários saudáveis foi apresentado a dois grupos de quatro colírios cada. Todos os colírios foram colocados em frascos idênticos sem rótulo. Em um grupo de quatro colírios, todos tinham conteúdos transparentes. No outro grupo, cada um dos quatro possuía uma substância de cor diferente. A cada um foi atribuído um número, e o voluntário foi solicitado a identificá-lo por meio da cor. Medimos o índice de acerto na identificação dos colírios dos dois grupos. Resultados: Os voluntários possuíam nível de formação desde Fundamental incompleto até Pós-Graduação completa, sendo 16 do sexo masculino (48%) e 18 do sexo feminino (52%), com idades variando de 21 até 87 anos. O índice de acerto no grupo de colírios coloridos foi de 88% e, no grupo de colírios transparentes, de 24%. Conclusão: O uso de colorações em colírios pode auxiliar na diferenciação entre os frascos e prevenir a identificação errônea.

ABSTRACT Objective: To reduce the inappropriate identification of eye drops, through the use of different colors. Methods: A group of 34 healthy volunteers was presented to two groups of four eye drops each. All eye drops were placed in identical, unlabelled vials. In one group, all four eye drops were transparent. In the other group, each had a different color. A number was assigned to each eye drop, and the volunteer was asked to identify it by color. We measured the correct index in the identification of the eye drops of the two groups. Results: The volunteers had a level of education from incomplete junior school to complete graduate course, with 16 males (48%) and 18 females (52%), age range of 21 to 87 years. The success rate in the group of colored eye drops was 88% and, in the group of transparent, 24%. Conclusion: The use of colorings in eye drops can help distinguishing the vials and preventing misidentification.

Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation

PURPOSE: Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs. MATERIALS AND METHODS: In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations. RESULTS: We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use. CONCLUSION: In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.

A study of clinical information of various package inserts: an approach to encourage adverse drug reaction reporting and emphasis on black box warning

Background: The package insert (PI) is important for providing accurate and reliable product information which is essential for the safe and effective use of medications.Methods: A total number of 115 PIs from pharmacological drug class such as antibiotics, drugs acting on central nervous system and drugs acting on endocrine system were collected from pharmacy store. Contents and presentation of the PIs was critically evaluated by comparing the information as listed in the Drugs and Cosmetics Rules, 1945.Results: The results were expressed under headings as listed in the Drugs and Cosmetics Rules, 1945. The information in the package inserts was inadequate in many aspects; for example, adverse drug reactions were not mentioned completely, information for special population and guidelines for use of the drugs also was lacking. Moreover, black box warning was seen only in few PI. For PI of antibiotics; legibility 80%, use in special populations 76.66%, undesirable effects 46.66%. For PI of CNS of legibility 60%, use in special populations 73.33%, undesirable effects 70%. For PI of endocrine system of legibility 70%, use in special populations 70%, undesirable effects 36.66%.Conclusions: The results reveal that, information relevant to the safe and effective use of medication was not mentioned in the analyzed package inserts. It is, therefore, recommended to update the existing package inserts based on criteria mentioned in the Schedule D of Drug and Cosmetic Act, 1945.

FDA's requirements for clinical pharmacology section of prescription drug labeling / 药物评价研究

FDA issued the Clinical Pharmacology Section of Labeling for Human Prescription Drug and Biological Products — Content and Format Guidance for Industry (final guidance)in December 2016.The Guidance stipulated that clinical pharmacology section must contain three subsections—echanism of action,pharmacodynamics,and pharmacokinetics;If necessary,it can be added to microbiology and pharmacogenomics subsections etc.,as well as explained that the contents of each subsection should be included,also discussed the writing general principles and the format of the section.This paper introduces the main contents of the guidance,with the hope of helping writing and supervision on our country labeling.

The Surveillance for Contents of Pharmacogenomics Information in Package Inserts and Interview Forms / 医薬品情報学

<b>Objective: </b>Pharmacogenomics (PGx) is the study of the relationship between the efficacy and/or safety of drugs and the genetic polymorphism.  Since PGx information can be used to personalize medical treatments, there has been a recent increase in the development of drug and companion diagnostic devices based on genome-wide analyses.  Therefore, we surveyed the contents of PGx information in package inserts and interview forms (IF) of Japanese pharmaceuticals, and investigated potential problems with the PGx information supplied by Japanese pharmaceuticals.<br><b>Methods: </b>PGx information content in package inserts and the IF used by Japanese pharmaceuticals was compared with that listed in the U.S. pharmaceuticals “Table of Pharmacogenomic Biomarkers in Drug Labeling.”<br><b>Results: </b>There were 166 PGx information content listings for 137 drugs described in the “Table of Pharmacogenomic Biomarkers in Drug Labeling.”  However, there were 31 PGx information content listings for 20 biomarkers of 24 drugs that were described in the U.S. but not the Japanese package inserts.  In addition, there was no PGx information for 17 biomarkers of 20 drugs in both the Japanese package inserts and the IF.  We additionally found that 57.7% of the biomarkers with PGx information listed in the package inserts were for drugs that are normally covered by <i>in vitro </i>diagnostic medical insurance.  These biomarkers were mainly the gene mutations and expression of the target molecules.<br><b>Conclusions: </b>The Japanese PGx information associated with gene mutations and expression of the target molecules was similar to the U.S. PGx information.  However, the contents of the PGx information for drug-metabolizing enzymes differed widely among each of the drugs.  In order to more effectively use PGx information, a more careful inspection of the information regarding efficacies and side effects will need to be undertaken to ensure better evaluations of patient therapies.

Description of Important Potential Risks of Japanese Risk Management Plan on Each Package Insert / 医薬品情報学

<b>Objective: </b>The Japanese risk management plan (RMP) contains the risk minimization action plans for important potential risks of drugs.  One of the basic risk minimization action plans is reminding on package insert; however, we found that some potential risks were not described in package inserts.  In this study, we investigated the description of potential risks on package inserts.<br><b>Design: </b>Document analysis.<br><b>Methods: </b>We collected all posted RMP documents and the package inserts of corresponding products from the Pharmaceutical and Medical Devices Agency website on January 31, 2015 and investigated the risk minimization action plans of important potential risk items and whether the items had been described in each package insert.<br><b>Results: </b>Of 268 important potential risk items in 81 products, 56 items were not described on package insert.  The major reason for not including the risk items on the package insert was “causality was not indicated sufficiently” and some items had no written reason.<br><b>Conclusion: </b>About 20% of important potential risks are not described in package inserts.  Because most post-marketing pharmacovigilance plans depend on spontaneous reporting by healthcare personnel, description on package insert, the most frequently referred drug information resource, should be considered.

A Study on the Validity of Dosage Adjustment Using Giusti and Hayton Equation for Renally Eliminated Drugs in Patients with Renal Dysfunction: A Systematic Literature Review / 医薬品情報学

<b>Objective: </b>To evaluate the validity of dosage adjustment of renally eliminated drugs using Giusti and Hayton method in patients with renal dysfunction by reviewing the pharmacokinetic data of the drugs.<br><b>Design: </b>A systematic literature review.<br><b>Methods: </b>Drugs with the following characteristics: ≥70% of the drug excreted in urine is the unchanged form and ≥20% of the drug in plasma is the unbound drug, were retrieved from Goodman and Gilman’s the Pharmacological Basis of Therapeutics, 12th edition.  For the drugs identified, the area under the concentration-time curves (AUC) obtained from pharmacokinetic studies in healthy subjects and patients with renal dysfunction were extracted from package inserts, interview forms, summary basis of approval, and by systematic review of the MEDLINE database.  Pharmacokinetic studies in children, patients with end-stage renal disease, patients on hemodialysis, and kidney transplanted patients were excluded from this review.  The observed AUC ratio (AUCR_observed) of a drug was calculated by dividing mean AUC of patients by that of healthy subjects, and stratified by creatinine clearance (CL_cr) into three categories: 50 to 79 mL/min, 30 to 49 mL/min, and 10 to 29 mL/min.  Theoretical AUC ratios (AUCR_predicted) of drugs for the respective CL_cr categories were calculated using Giusti and Hayton method.<br><b>Results: </b>Twenty-six drugs met our study criteria, and 43 data sets were obtained from the data sources.  The AUCR_observed deviated from the AUCR_predicted by more than ±50% in 3 of 35 (9%) data sets for CL_cr 50 to 79 mL/min, 4 of 39 (10%) data sets for CL_cr 30 to 49 mL/min, and 7 of 29 (24%) data sets for CL_cr 10 to 29 mL/min.<br><b>Conclusion: </b>Since AUCR_predicted calculated by Giusti and Hayton method erratically over- or under-estimates the maintenance doses in patients with reduced renal function, the use of AUCR_observed is preferred for dose adjustment in these patients.

Relevance of variation in use of terminology to define generic pharmaceutical products / Relevancia de la variación en el uso de la terminología para definir los medicamentos genéricos

The World Health Organization (WHO) promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country) and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies.

La Organización Mundial de la Salud (OMS) promueve el uso de políticas de medicamentos genéricos para estimular la competencia en el sector farmacéutico, reducir los precios y aumentar el acceso a los medicamentos. Sin embargo, hay poca información sobre la aplicación de dichas políticas por parte de los países. Este artículo describe la terminología empleada por los organismos regulatorios nacionales para definir los medicamentos genéricos frente a las especialidades farmacéuticas de marca en los países en desarrollo, incluidos los de América Latina, así como las dificultades que se encuentran en la aplicación de las directrices de la OMS, como por ejemplo en el etiquetado. El autor llega a la conclusión de que la variación en la terminología de los medicamentos genéricos en estos países es resultado del contexto institucional (es decir, el sector público y el ordenamiento jurídico-administrativo del país) y de los legados de las políticas, como los regímenes de propiedad intelectual, y destaca la necesidad de analizar más a fondo los reglamentos farmacéuticos a fin de conocer mejor los obstáculos y las implicaciones de las políticas en materia de medicamentos genéricos.

Uso de medicamentos off-label e não licenciados em unidade de tratamento intensivo neonatal e sua associação com escores de gravidade / Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores

OBJETIVO: Avaliar a frequência da prescrição de medicamentos de uso não licenciado (UL) e off-label (OL) em recém-nascidos internados em unidade de tratamento intensivo neonatal de hospital de nível terciário e verificar a associação do seu uso com a gravidade dos pacientes. MÉTODOS: Estudo observacional de coorte dos medicamentos prescritos no período de 6 semanas da internação de neonatos, entre julho e agosto de 2011. Os medicamentos foram classificados em UL e OL para dose, frequência, apresentação, faixa etária e indicação, de acordo com bulário eletrônico aprovado pela Food and Drug Administration. Os pacientes foram acompanhados até alta hospitalar ou 31 dias de internação, com registro diário do Neonatal Therapeutic Intervention Scoring System. RESULTADOS: Foram identificados 318 itens de prescrição para 61 pacientes (média de cinco itens/paciente) e apenas 13 pacientes com uso de medicamentos adequados (21%). Identificaram-se prevalências de 7,5% para prescrições UL e de 27,7% para OL. O uso OL mais prevalente foi para medicamentos não padronizados para faixa etária - 19,5%. Computaram-se 57 medicações - um paciente recebeu 10 fármacos UL/OL na internação. A prevalência de usos OL foi maior em prematuros < 35 semanas e nos com escores de gravidade mais elevados (p = 0,00). CONCLUSÕES: A prevalência de neonatos expostos a medicamentos UL/OL durante a internação hospitalar foi elevada, especialmente naqueles com maior escore de gravidade no Neonatal Therapeutic Intervention Scoring System. Embora haja apreciação geral de que neonatos, especialmente pré-termo, tenham alta taxa de uso de medicamentos, uma avaliação incluindo diferentes culturas e países é necessária para priorizar áreas de pesquisa futura na farmacoterapêutica dessa população vulnerável.

OBJECTIVE: To analyze the frequency of unlicensed (UL) and off-label (OL) prescriptions in neonates admitted to the neonatal intensive care unit of a tertiary care hospital and to determine their association with patients' severity. METHODS: Observational cohort study including drugs prescribed during hospitalization of neonates over a 6-week period between July and August 2011. The drugs were classified as UL and OL for dose, frequency, presentation, age group, or indication, according to an electronic list of drugs approved by the Food and Drug Administration. Patients were followed until hospital discharge or 31 days of hospitalization, with daily records of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS: We identified 318 prescription items for 61 patients (average of five items/patient); there were only 13 patients with appropriate use of medications (21%). A prevalence of 7.5% was identified for UL prescriptions and 27.7% for OL, and the most prevalent OL use was that related to age group - 19.5%. Fifty-seven medications were computed - one patient received 10 UL/OL drugs during hospitalization. The prevalence of OL uses was higher in preterm infants < 35 weeks and in those with higher severity scores (p = 0.00). CONCLUSIONS: The prevalence of neonates exposed to UL/OL drugs during hospitalization was high, especially for those with higher NTISS scores. Although there is general appreciation that neonates, especially preterm infants, have a high rate of drug use, an assessment including different cultures and countries is still needed to prioritize areas for future research in the pharmacotherapy of this vulnerable population.

Análise da rotulagem de medicamentos semelhantes: potenciais erros de medicação / Analysis of similar drug labeling: potential medication errors

OBJETIVO: Este trabalho objetivou analisar as embalagens e rótulos de medicamentos, identificando semelhanças entre os mesmos que possam conduzir a erros de medicação passíveis de ocorrer por troca, em diferentes setores da farmácia de um hospital universitário do nordeste do Brasil. MÉTODOS: Estudo observacional e transversal, que abrangeu 300 apresentações farmacêuticas, sendo (150 duplas) fotografadas no período de maio a dezembro de 2010. A análise de concordância dos dados referente às fotos de embalagens e rótulos possivelmente semelhantes foi validada utilizando o índice Kappa. RESULTADOS: Do total de medicamentos avaliados (n = 150), cerca de 43 por cento dos "possivelmente semelhantes" estavam na farmácia central (n = 65) e se relacionaram a soluções parenterais de pequeno volume. A força de concordância interobservadores na categoria "muito semelhante entre si" foi considerada "satisfatória" (índice Kappa = 0,584) em 90,66 por cento dos medicamentos avaliados (n = 136). A análise do Kappa geral do estudo foi de 0,488. As variáveis com significância estatística foram: "mesma cor do rótulo ou embalagem", com os respectivos percentuais, tanto para embalagens primárias como secundárias (52 por cento-44 por cento), com p = 0,028. A variável "mesma cor das apresentações farmacêuticas" obteve valores e significância estatística semelhantes à variável anterior. Quanto à variável "mesma disposição dos dizeres", os valores encontrados para ambas as embalagens foram próximas a 50 por cento, com p = 0,001 e, para a variável "mesma cor dos dizeres", os percentuais encontrados foram: (50,7 por cento-44 por cento) (p = 0,008). CONCLUSÃO: Nossos resultados identificaram semelhanças relativas à rotulagem de medicamentos com potencial, principalmente, para erros de dispensação, armazenamento e administração se medidas preventivas não forem adotadas.

OBJECTIVE: This study aimed to examine drug packaging and labeling, identifying similarities among them that may lead to medication errors, which may occur by unintentional substitution, in different sectors of the pharmacy of a university hospital in northeastern Brazil. METHODS: Cross-sectional observational study, which included 300 pharmaceutical presentations (150 pairs) that were photographed from May to December 2010. Concordance analysis of data related to the pictures of possibly similar packaging and labels was validated using the Kappa index. RESULTS: Of all drugs evaluated (n = 150), about 43 percent of "possibly similar drugs" were in the central pharmacy (n = 65) and were related to small-volume parenteral solutions. The strength of interobserver agreement in the category "very similar to each other" was considered "satisfactory" (Kappa = 0584) in 90.66 percent of the drugs evaluated (n = 136). The overall Kappa analysis of the study was 0.488. Variables with statistical significance were: "same color label or packaging", with the respective percentages for both primary and secondary packaging (52 percent-44 percent), p = 0.028; the variable "same color of drug presentation" obtained similar values and statistical significance to the previous variable; for the variable "same arrangement of words", the values found for both packages were close to 50 percent, p = 0.001; and for the variable "same color of the words", the percentages were: (50.7 percent - 44 percent) (p = 0.008). CONCLUSION: Our results indicate similarities related to the labeling of drugs with potential for errors, especially in dispensing, storage, and administration if preventive measures are not adopted.

Off-label or Unlicensed Drug Prescriptions in Child and Adolescent Psychiatry

The purpose of licensing system is to ensure that the medicines are examined for safety, efficacy and quality. Nevertheless, off-label or unlicensed drug usages in pediatric practice is widespread in Korea and worldwide. Psychotropics are one of the most commonly used off-label or unlicensed drugs. The most valid approach to face this dilemma will be to have more evidences from pediatric pharmacological studies. Clinicians, in addition, need to monitor closely their off-label or unlicensed drug prescriptions to minimize the trial and error in practice. Researchers should publish their experiences and provide guidelines. Pharmaceutical companies, regulatory authorities, and consumer organizations should endeavor altogether for the children's right to get safe and efficacious drugs as adults do. Here, the definition as well as the current status of off-label and unlicensed drug prescriptions will be introduced. Critical issues regarding the off label drugs are discussed. In addition, I will describe the present condition as to the off-label and unlicensed drugs in child and adolescent psychiatry and the authorization process of off-label drug prescription in Korea. Lastly, direction we should like to take in this field will be mentioned.

Off-label drug use in a pediatric intensive care unit.

Objective. To determine the extent and nature of off-label drug use in children admitted to a Pediatric Intensive Care Unit (PICU) Methods. This prospective exploratory study was conducted in a tertiary care hospital in a metropolitan city in India after obtaining clearance from the institutional ethics committee. Subjects admitted in PICU from February-August 2006 were enrolled in the study. In addition to the demographic data and diagnosis, details of drugs prescribed (name, dose and route and frequency of administration) were obtained from hospital records. British National Formulary 2005 was used to determine if the prescriptions were off-label and if so, they were categorized as off-label for age, indication, dosage or frequency and route of administration. Descriptive statistics was used to determine the proportion of off-label drug use. Fischer’s exact test was used to determine if there was significant difference (P<0.05) in off-label use between patients with multiple system affection and those with single system affection and between those requiring artificial ventilatory support and those not requiring it. Results. Three hundred subjects received 2237 analyzable prescriptions. Of these 1579 (70.58%) prescriptions were offlabel in nature. Off-label drug use was prevalent in all age-groups and in all systemic afflictions. The proportion of off-label drug use was not influenced by severity of illness, as judged by involvement of multiple systems or need for ventilatory support. The list of off-label drugs used included old as well as new molecules. Most commonly used drugs in PICU were also the most common off-label drugs. Conclusion. Off-label drug use is highly prevalent in PICU settings.

Communication Effects of Written Drug Information on Patient Attitude, especially Those of Risk Information / 薬剤疫学

Objective : To evaluate communication effects of the intervention by written risk information on prescribed drugs and explore the influencing factors.<BR>Design : A randomized prospective controlled trial.<BR>Setting : An outpatient unit in a medical center.<BR>Patients : 243 outpatients prescribed antihypertensive drugs.<BR>Intervention : Patients were randomized into either the study or control group. The study group received sheets showing risk information in addition to drug's name and efficacy while the control group received those without risk information. Patients were requested to complete a questionnaire before and 1 month after receiving information.<BR>Main outcome measures : The communication effects, defined in terms of patient satisfaction, helpfulness of the sheets, reassurance about taking drugs and compliance evaluated by himself.<BR>Results : Of 243 patients, 123 completed the second questionnaire. Of those 123, the study group patients were significantly more satisfied (p=0.035). For other 3 measures, there were no significant differences between the study and control groups. But almost all patients regarded the sheets helpful. After receiving the sheets with or without risk information, 67 (61.5%, 109 answered) were reassured and the compliance was said to be improved with 32 (28.1%, 114 answered).<BR>From the exploratory analysis of 112 patients having completed both questionnaires, patients who evaluated the sheets helpful tended to be more reassured. The compliance of patients who were reassured tended to be better.<BR>Conclusion : Patients regarded the written drug information as a helpful medium and were more satisfied with risk information. Irrespective of whether risk information was included, reassurance and better compliance were attained by the written drug information.

METHOD FOR ULTRASTRUCTURAL LOCALIZATION OF N ACETYLCHOLINE RECEPTOR / 第二军医大学学报

A method by using ?-BT-HRP conjugate to localize N-acetylcholinc receptor of neuromuscular junction was described.Thin strips of fresh muscle were incubated with ?-BT-HRP conjugate at a concentration of 1?10-7 M in Tyroid's solution and then reacted with Karnovsky's DAB medium.There were obviously brownish red positive deposits to constitute various vesicular forms seen under a light microscope. Under an electron microscope we can see positive deposits that were localized both on the presynaptic and postsynaptic membra-nes. The binding activity and reliability of a-BT-HRP were discussed.