Using Package Inserts to Disseminate Information Regarding Drug Interactions Mediated by CYP3A Inhibition: Status and Issues / 医薬品情報学

Objective: In Japan, the Guideline on Drug Interaction for Drug Development and Appropriate Provision of Information (GL) was notified in 2018. In the GL and the associated document, it was determined that package inserts of drugs which need to be categorized as precaution due to the significant degree of drug interactions by CYP3A inhibition should describe possible perpetrator drugs using designated expressions, such as “strong CYP3A inhibitor.” For contraindication, it was decided that all drugs should be described individually. In 2021, as supplementary information to the GL, a list of CYP substrates, inhibitors and inducers, classified based on interaction strength and CYP isoenzymes (i.e., the drug list), was published. In this study, we aimed to survey the information on drug interactions by CYP3A inhibition described in the package inserts based on information in the drug list, and to clarify the status and issues.Methods: The package inserts of 24 substrate drugs of CYP3A with contraindications for itraconazole, a strong CYP3A inhibitor, were examined, and the descriptions of strong, moderate, and other CYP3A inhibitors were studied.Results: The frequencies of contraindication for strong CYP3A inhibitors were cobicistat (75%), grapefruit juice (0%), ritonavir (92%), voriconazole (67%), clarithromycin (50%), ceritinib (0%), and posaconazole (33%). On the other hand, some CYP3A substrate drugs was contraindicated with moderate CYP3A inhibitors but not with these strong CYP3A inhibitors. Furthermore, 19 CYP3A inhibitors, which were not on the drug list published in 2021, were identified as contraindications for co-administration. Majority of these were protease inhibitors, and some have been discontinued or not available in Japan.Conclusion: The findings of this study imply the necessity of organizing scientific description based on the GL strength classification. Moreover, it is important to disseminate the information and precautions for drug interactions provided in the package inserts to medical practice.

Análise da qualidade das evidências científicas sobre a eficácia e segurança nas bulas de anticoagulantes orais diretos comercializados no Brasil / Analysis of the quality of scientific evidence on efficacy and safety in the package leaflets of direct oral anticoagulants marketed in Brazil

Objetivo: Identificar e analisar a qualidade das evidências científicas sobre a eficácia e segurança dos anticoagulantes orais direto (DOAC) disponíveis nos ensaios clínicos referenciados nas bulas dos medicamentos comercializados no Brasil. Método: Trata-se de um descritivo documental dividido em duas etapas, sendo elas: (i) identificação e análise da disponibilidade das referências bibliográficas contidas nas bulas dos DOAC e (ii) análise da qualidade dos estudos contidos nas bulas através da ferramenta da Cochrane Risk of Bias RevMan versão 5.4. Foram analisados setes domínios de importâncias para ensino clínico, sendo que cada domínio foi classificado como alto, incerto ou baixo risco de viés, segundo a avaliação dos colaboradores. Resultados: Foram analisadas 10 bulas destinadas aos profissionais da saúde. Sendo que destas, foram avaliados 25 ensaios clínicos. A análise da qualidade das evidências científicas, referenciadas nas bulas para profissionais dos DOAC, mostrou que os estudos citados apresentaram consistência metodológica. Entretanto, na maioria dos estudos, os domínios foram classificados como viés incerto, ou seja, não foi possível identificar como esses pontos foram abordados nos estudos. Conclusão: Portanto, o presente estudo evidenciou que a qualidade dos ensaios clínicos referenciados nas bulas dos DOAC apresentou incertezas metodológicas em seus ensaios. Sugere-se a necessidade de normativas que estabeleçam atualizações do conteúdo informativo presente nas bulas profissionais e estabeleçam descrição dos métodos de forma clara e coesa (AU).

Objective: Identify and analyze the quality of scientific evidence on the efficacy and safety of direct oral anticoagulants (DOAC) available in clinical trials referenced in the package leaflets of drugs marketed in Brazil. Method: This is a descriptive documentary study divided into two stages: (i) identification and analysis of the availability of the bibliographic references contained in the package leaflets of DOACs and (ii) analysis of the quality of the studies contained in the package leaflets through the Cochrane Risk of Bias RevMan tool version 5.4. Seven domains of importance for clinical teaching were analyzed, and each domain was classified as high, uncertain or low risk of bias, according to the assessment of the collaborators. Results: Ten package leaflets intended for health professionals were analyzed. Of these, 25 clinical trials were evaluated. The analysis of the quality of the scientific evidence referenced in the package leaflets for health professionals showed that the cited studies presented methodological consistency. However, in most studies, the domains were classified as uncertain bias, i.e., it was not possible to identify how these points were addressed in the studies. Conclusion: Therefore, the present study evidenced that the quality of clinical trials referenced in the package leaflets of DOACs presented methodological uncertainties in their trials. It is suggested the need for regulations that establish updates of the information content present in the professional package inserts and establish a description of the methods in a clear and cohesive way (AU).

Medication package inserts do not present adequate information on potential risks for older adults in Brazil / Bulas de medicamentos não apresentam informações adequadas sobre potenciais riscos para idosos no Brasil

OBJECTIVE: To compare information on the risks of potentially inappropriate medications (PIMs) for older adults in the Beers criteria with data in the package inserts made available by the Brazilian Health Regulatory Agency. METHODS: This is an observational, cross-sectional study that compared information on the package inserts of 33 brand-name drugs in the Brazilian market with specific recommendations for older adults contemplated in the Beers criteria, categorizing them into: complete, incomplete, absent, or discrepant. RESULTS: Among the analyzed package inserts, 21.21% did not present a specific section dedicated to the use of these drugs by older adults and data were scattered throughout the text; 63.64% were classified as incomplete; 33.33% lacked data; and 3.03% had discrepant information. CONCLUSION: The analyzed package inserts presented incomplete data or lacked information characterizing the drugs as PIMs for older adults. This study demonstrated that some package inserts of drugs used in Brazil are not satisfactory, warranting higher caution in the medical community when prescribing these medications and guiding patients

OBJETIVO: Comparar as informações sobre os riscos de medicamentos potencialmente inapropriados (MPIs) para idosos contidas nos critérios Beers com as informações presentes nas bulas para profissionais de saúde disponibilizadas pela Agência Nacional de Vigilância Sanitária no Brasil. METODOLOGIA: Estudo observacional e transversal que comparou informações das bulas para profissionais de saúde de 33 medicamentos de referência no mercado brasileiro com recomendações específicas para idosos contempladas nos critérios Beers e que foram categorizadas em: completas, incompletas, ausentes ou discrepantes. RESULTADOS: Dentre as bulas dos MPIs analisadas, 21,21% não apresentam seção específica destinada ao uso desses medicamentos por idosos, nas quais as informações estão dispersas pelo texto; 63,64% delas foram classificadas como incompletas; 33,33% tinham informações ausentes; e 3,03% com informações discrepantes. CONCLUSÃO: As bulas analisadas apresentaram dados incompletos ou não apresentam qualquer informação que caracterizasse o medicamento como MPI para idosos. Este estudo demonstra que algumas bulas de medicamentos utilizados no Brasil não estão satisfatórias, sugerindo maior cautela à comunidade médica na prescrição e na orientação aos seus pacientes

Adverse drug reactions induced by hydroxychloroquine in the treatment of oral lichen planus: a report of 13 cases / 口腔疾病防治

Objective @# To analyze the adverse drug reaction（ADR） reports of hydroxychloroquine for clinical medication safety. @* Methods@#The ADR reports of hydroxychloroquine between May 2019 and May 2021 were analyzed. Age, reasons for drug use, time of ADR, combined drug use, and ADR outcomes were statistically analyzed. @*Results@# No severe ADR was reported. Patients over 60 years old accounted for 53.85% of the total cases, and the time of ADR appearance was significantly earlier among those under 60 years old. A total of 61.54% of ADRs were involved in multiple organs, and optic neurotoxicity was reported in 46.15% of cases. @*Conclusion@# In the treatment of oral lichen planus with hydroxychloroquine, adverse drug reactions should be monitored, and increased attention should be given to patients over 60 years old to ensure the safety of this medication.

Quality of clinical studies present in the package inserts of coagulation factors used in the treatment of hemophilia

ABSTRACT Objective To identify and analyze the quality of scientific evidence from clinical efficacy studies present in the package inserts of coagulation factors, used in the treatment of hemophilia A and B. Methods Documentary study developed in two stages. The first stage consisted of identifying the medicine packages inserts electronically registered in the Brazilian Health Regulatory Agency, and analyzing the availability of the bibliographic references cited therein. This analysis was conducted in the PubMed, SciELO, Google Scholar, and Web of Science databases. The second step was the analysis of the methodological quality of the efficacy studies. Two trained researchers used the Cochrane Collaboration Risk of Bias version 5.1.0 tools for methodological quality analysis, and Review Manager 5.4 software to generate the risk of bias graph. Results Of the 17 medicines listed, 7 had referenced package inserts. Of these, 10 studies were eligible for analysis of methodological quality. More than half of the analyzed studies did not control for selection, performance, and detection bias. A total of 100% controlled attrition and reporting biases, and 50% had a high risk of conflict of interest. Conclusion The biases present are significant and may have influenced the overestimation of the effects of the outcomes of each of the studies.

Amamentação e utilização de medicamentos: qual a orientação presente nas bulas de anticoncepcionais e anti-infecciosos? / Breastfeeding and drug use: what is the orientation found in drug package inserts of contraceptives and anti-infective agents?

Resumo O objetivo deste artigo é avaliar a concordância entre bulas e fontes bibliográficas baseadas em evidências científicas quanto à presença de contraindicação do uso de anticoncepcionais e anti-infecciosos durante a amamentação. Foram selecionados medicamentos anticoncepcionais e anti-infecciosos, segundo a ATC, com registro na ANVISA e presentes nas fontes bibliográficas: Manual Amamentação e Uso de Medicamentos e Outras Substâncias, Medications and Mother's Milk, LactMed®, Micromedex® e UpToDate®. As informações foram extraídas das seções "Contraindicações" e "Advertências e precauções" das bulas e comparadas com as informações das fontes. Foi avaliada a presença de informação contraindicando o uso do medicamento durante a amamentação. Em cinco (55,5%) dos nove anticoncepcionais foi verificada contraindicação na bula. Entre as fontes bibliográficas, o percentual variou de 0% a 55,5%, dependendo da fonte. Para os anti-infecciosos, o percentual de contraindicação foi de 46,3% na bula, variando de 0% a 12,9% nas fontes. Existe concordância entre as bulas e as fontes bibliográficas com relação aos anticoncepcionais; no caso dos anti-infecciosos, as bulas apresentam contraindicação para o uso durante a amamentação com mais frequência.

Abstract This article aims to evaluate the conformity between drug package inserts (DPIs) and evidence-based bibliographic sources regarding the presence of contraindications to the use of contraceptives and anti-infective agents during breastfeeding. Contraceptive and anti-infectives were selected, according to ATC, with the updated record in the ANVISA and present in the bibliographic sources Breastfeeding and Use of Medicines and Other Substances, Medications and Mother's Milk, LactMed®, Micromedex® and UpToDate®. Information was extracted from the DPI "Contraindications" and "Warnings and precautions" sections and compared with the information in the bibliographic sources. The contraindication of the drug during breastfeeding was evaluated. Contraindications were found in the DPIs of five (55.5%) of the nine contraceptives. The contraindication percentage ranged from 0 to 55.5% among the bibliographic sources, depending on the source. The percentage was 46.3% in the DPIs, ranging from 0 to 12.9% in the bibliographic sources for anti-infectives. There is an agreement between the DPIs and the bibliographic sources regarding contraceptives; regarding anti-infectives, the DPIs are more often contraindicated for use during breastfeeding.

Deprescribing benzodiazepines: Do Brazilian package inserts address this issue? / Desprescrição de benzodiazepínicos: As bulas brasileiras abordam essa temática?

OBJECTIVE: To analyze the presence and quality of content on drug deprescribing in Brazilian package inserts for benzodiazepine drugs. METHODS: Documentary study where we analyzed data on deprescribing extracted from electronic package inserts of drugs containing benzodiazepines; these documents were available at the Brazilian Health Surveillance Agency website. Our search was performed independently by 2 researchers who used the following keywords: "deprescription," "withdrawal," and "tapering." The deprescribing plan, when presented by the package insert, was compared to deprescribing protocols for benzodiazepines found in the literature. Moreover, we assessed the presence of guidance on the maximum length of treatment and risks of long-term use. RESULTS: We found 12 package inserts for benzodiazepines and 100% of them suggested gradual withdrawal; only 1 (8.33%) suggested a systematized deprescribing plan. One document (8.33%) did not offer guidance on maximum treatment duration. Eleven (91.67%) had the information on long-term use possibly causing dependence or tolerance, and 1 (8.33%) did not describe the risks of continuous use. CONCLUSIONS: It is known that benzodiazepines should be withdrawn in a gradual and schematized manner, but package inserts do not currently bring this information in detail. It is of utmost importance that health professionals be educated on their conduct, hence the necessity for updating medication package inserts.

OBJETIVO: Analisar a presença e a qualidade do conteúdo sobre desprescrição em bulas brasileiras de benzodiazepínicos. METODOLOGIA:Estudo do tipo documental, em que foram analisados dados sobre a desprescrição extraídos de bulas eletrônicas de medicamentos que contêm benzodiazepínicos disponibilizadas na página eletrônica da Agência Nacional de Vigilância Sanitária. A busca foi realizada de forma independente por dois pesquisadores que utilizaram as palavras-chave "desprescrição", "retirada" e "redução". Para fins de comparação, quando a bula apresentou esquema de desprescrição, este foi comparado com protocolos de desprescrição de benzodiazepínicos encontrados na literatura. Além disso, foi analisada nas bulas a existência de orientações quanto ao tempo máximo de uso e os riscos do uso prolongado. RESULTADOS: Foram encontradas 12 bulas de benzodiazepínicos e 100% delas sugeriram a redução gradual do medicamento; apenas uma (8,33%) sugeria o esquema sistematizado de desprescrição. Uma (8,33%) não apresentou orientações quanto ao tempo máximo de uso. Onze (91,67%) continham a informação de que o uso prolongado pode causar dependência ou tolerância e uma (8,33%) não descrevia os riscos do uso contínuo. CONCLUSÕES: Sabe-se que os benzodiazepínicos devem ser retirados de forma gradual e esquematizada, porém, atualmente, as bulas não trazem essas informações de forma detalhada. É de suma importância que os profissionais de saúde sejam orientados quanto a sua conduta e, por isso, há grande necessidade de atualização das bulas.

Análise técnica das bulas dos antibióticos utilizados no tratamento da tuberculose / Technical analysis of the leaflets of antibiotics used in the treatment of tuberculosis

Objetivo: Descrever a apresentação das informações presentes nas bulas dos antibióticos utilizados no tratamento da tuberculose conforme as exigências da ANVISA. Metodologia: Trata-se de um estudo exploratório, descritivo e reflexivo da estrutura e conteúdo das bulas adquiridas através do site da Agência Nacional de Vigilância Sanitária. Verificou-se se os itens apresentados são aqueles exigidos pela portaria regulamentadora. As informações destinadas ao paciente foram refletidas, buscando compreender se essas são objetivas, organizadas e escritas numa linguagem compreensível ao público. Resultados: Detectou-se, na estrutura geral, a ausência de alguns tópicos preconizados pela portaria regulamentadora. Na seção de informação aos pacientes notou-se ausência de algumas informações, bem como informações com variado grau de precisão, a exemplo da ausência da ação esperada do medicamento, imprecisão nos cuidados de armazenamento, e uso de frases subjetivas como 'refeições leves' e 'problemas no sangue'. Conclusão: O desenvolvimento desse estudo corrobora com outras pesquisas realizadas, onde algumas exigências legais não foram cumpridas. É possível inferir que as bulas atendem a maioria dos requisitos, porém, necessitam de adequações. Salienta-se a importância dos profissionais de saúde esclarecerem dúvidas sobre o uso desses antibióticos aos seus usuários, e assim contribuir para uma terapia medicamentosa de sucesso

Objective: Describe the presentation of the information present in the package inserts of the antibiotics used in the treatment of tuberculosis as required by ANVISA. Methodology: This is exploratory, descriptive and reflective study of the structure and content of the package inserts acquired through the website of the National Sanitary Surveillance Agency. It was verified that the items presented are those required by the regulatory authority. The information destined to the patient was reflected, trying to understand if these are objective, organized and written in a language understandable to the public. Results: In the general structure, we detected the absence of some topics recommended by the regulatory decree. In the section of information to the patients it was noticed absence of some information, as well as information with varied degree of precision, such as absence of expected drug action, inaccuracy in storage care, and use of subjective phrases such as 'light meals' and 'blood problems'. Conclusion: The development of this study corroborates with other researches carried out, where some legal requirements were not fulfilled. It is possible to infer that the package inserts meet most requirements, but still require adjustments. It is important to emphasize the importance of health professionals to clarify doubts about the use of these antibiotics to their users, and contribute to the successful drug therapy.

A study on the evaluation of drug package inserts: a prospective observational study

Background: The package inserts are an important source of information for the patient and the prescribers which are often incomplete in terms of information. Not many of them are patient friendly, usage of technical terms further complicates the scenario amidst inadequate doctor-patient ratio. Aim of the study was to evaluate the completeness of package inserts.Methods: Hundred package inserts were collected from June 2018 to September 2018 from nearby pharmacies and drug store of a tertiary care hospital, Government Medical College, Akola and evaluated in terms of completeness as per guidelines mentioned in the section D of Drug and Cosmetics Act 1945, language used and addressed to whom. Each guideline followed under section D was given a score of 1 and absence 0 depending upon which grouped as Grade A (>15), Grade B (10-15), Grade C (<10). Result was analysed in Microsoft Excel 2010 expressed in percentage and whole numbers.Results: Out of the 100 package inserts evaluated the guidelines like mentioning of special circumstances like pregnancy was present in (98%), undesirable effects in 98%. All of them used English with 3% having combination with regional language, 70% had no mention as to whom it is addressed. Grades allotted after evaluation A, B, C, 24%, 74%, 2%.Conclusions: The present study showed though improvement occurred deficiencies should be corrected and properly scrutinised for better compliance of the patient and effective drug use and to step up the healthcare services in society.

Analysis of drug promotional literature and its abidance to WHO guidelines

Background: Drug promotional literature (DPL) is used by the pharmaceutical companies for promotion of their drug. It is the commonest source for providing information about the drug to the physician. According to WHO promotional literature should be reliable, truthful, informative, balanced and up to date.Methods: Study was conducted in Department of Pharmacology, Muzaffarnagar Medical College. 200 drug promotional literatures like advertisements published in medical journal, package insert of medicinal products and brochures were collected and analysed according to WHO criteria.Results: Total 200 promotional literatures were analysed. 100 promotional literatures were from the medical journal, 50 were package inserts of medicinal products and 50 were medicinal brochures. On assessing DPL using WHO criteria, all DPL mentioned brand names and dosage form (100%). Most of them published the generic name (98.5%), therapeutic uses (78%), side- effects (75%), dosage regimen (70%), contraindication (62.5%), warnings (55%), drug interaction (54%), precaution (50%), reference to scientific literature (45%), name of manufacture and distributor (99%), address of manufacturer and distributor (50%). Out of 200 DPL only 151 DPL contain references to scientific literature, 88 DPL references were retrievable and 63 were non retrievable.Conclusions: Our study shows although pharmaceutical companies are trying to adhere to the WHO criteria it is not fulfilled. As DPL are an important source of seeking information by the medical practitioner who rely on them to impart treatment to the patient, strict steps to regulate fulfilment of the WHO criteria should be taken by the government and authorities.

Validation of a new tool for evaluating subjects' satisfaction with medicine package leaflets: a cross-sectional descriptive study

ABSTRACT BACKGROUND: Package leaflets of medicines need to be intelligible, but tools for their evaluation are scarce. OBJECTIVE: To validate a new tool for assessing subjects' satisfaction with medicine package leaflets (LiS-RPL). DESIGN AND SETTING: Cross-sectional descriptive study conducted in two regions of Portugal (Lisbon and Centre). METHODS: 503 participants (53.1% male) were selected according to convenience and homogenously distributed into three groups: 1 to 6; 7 to 12; and > 12 years of schooling. LiS-RPL was developed based on international regulation guidelines and was initially composed of 14 items. Twelve package leaflets were tested. Dimensionality calculations included: exploratory factor analysis and minimum rank factor analysis; Kaiser-Meyer-Olkin index and Bartlett's sphericity test to assess matrix adequacy for exploratory factor analysis; exploratory bifactor analysis with Schmid-Leiman solution to detect possible existence of a broad second-order factor; and Bentler's Simplicity Index and Loading Simplicity Index to assess factor simplicity. Diverse coefficients were calculated to assess reliability. RESULTS: Minimum rank factor analysis detected a two-factor or single-factor structure. Exploratory factor analysis with 12 items showed a two-factor structure, explaining 69.11% of the variance. These items were strongly correlated with each other (r = 0.80). Schmid-Leiman: all items seemed to represent the general factor (loadings above 0.50), which was 76.4% of the extracted variance. Simplicity indices were good (percentile 99): Bentler's Simplicity Index of 0.99 and Loading Simplicity Index of 0.48. Internal consistency indexes indicated good reliability. LiS-RPL was shown to be homogenous. CONCLUSION: LiS-RPL is a validated tool for evaluating subjects' satisfaction with medicine package leaflets.

A study on awareness about package inserts among postgraduate medical students: an observational questionnaire based study

Background: A package insert is a document approved by the administering licensing authority, which is provided with the package of a drug. A good package insert can prove to be of immense help to doctors as they are evidence based and are updated from time to time. The objective to study the awareness about package inserts among postgraduate medical students.Methods: The present study was a cross-sectional observational study carried out on 68 postgraduate medical students of Acharaya Shri Chander College of Medical Sciences and Hospital Sidhra, Jammu (J & K) in the month of February 2017 after taking approval from the institutional ethical committee. Pre-validated self-administered questionnaire was used to elicit responses from the students. The questionnaire consisted of specified questions regarding knowledge and opinion about package inserts.Results: In the present study, 86.7% of the students understand the relevance of Package inserts (PIs). About 72% of the students think that PIs are a necessary add-on to drug information and 70.6% of the students think that information given on package inserts is necessary for the patients. However, only 2.9% of the students had the knowledge of Drug Acts governing the information to be provided on PIs in India. About 86.8% of the students think that PIs should also be in regional language apart from in English language.Conclusions: It was found from the present study that the majority of the postgraduate students were aware about the package inserts available with the medicines but the information provided on package inserts was not optimally used by them. To achieve the target of optimally utilization of information provided in the package inserts, the PIs should be designed by considering the needs and information of two differently educated target groups i.e; patients and doctors.

Investigation and Analysis of Medication Information Labeling in 157 Package Inserts of Anticancer Drugs / 中国药房

OBJECTIVE： To investigate and analyze medication information labeling in package inserts of anticancer drugs， and to provide reference for clinical rational use. METHODS： The package inserts of anticancer drugs were collected from drug catalogues of 3 Third Grade Class A hospitals in Nanjin. Common problems of drug package inserts （whether the main contents arweree contradictory or not and whether the contents were fully expressed， etc.）， complete specific labeling items （detailed contents of “ADR” “contraindication” “precautions” and other items）， detailed intravenous injection dispensing guidance （solvent selection， precautions during dispensing， etc.）， package insert labeling difference of drugs with same general name and route of administration were evaluated according to Drug Package Inserts and Label Management Regulation，Regulations for Chemical Drugs and Biological Products for Treatment. RESULTS： A total of 157 package inserts for anticancer drugs were collected and divided into domestic drugs （80 pieces） and imported drugs （77 pieces） according to the source as well as also divided into oral preparation （44 pieces） and injection （113 pieces）. The common problems of package inserts for anticancer drugs contained contradictory main contents， incomplete description， Chinese character errors， missing items and simple description of drug interactions， etc. Compared with domestic or oral anticancer drugs， the labeling rate of each item in the import or injection anticancer drug package inserts was higher， but specific labeling items such as prevention and treatment of vomiting （＜20％） under “precautions” and interference of drugs on clinical tests （＜40％） were lower. The labeling rate of serious ADR after large dose or long-term use was all less than 41％ under the item of “drug overdose” （except for imported drugs）. The labeling rate of intravenous dispensing guidance of imported anticancer drug injection package inserts about preparations was higher than that of domestic ones. There were differences in labeling items as “precautions” （30/56，53.57％）， “pharmacological toxicology” （29/56，51.79％）， “contraindication” （26/56，46.43％） among 56 groups of drug package inserts with same general name and route of administration. CONCLUSIONS： The labeling items for drug package inserts of anticancer drugs need to be further standardized and improved. It is recommended that the relevant departments force pharmaceutical manufacturers to regularly supplement the deficiencies in the package inserts to improve the safety of drug use in clinic.

Analysis of Pediatric Medication Information Labelling in 46 Pieces of Package Inserts for Skin External Drugs in Our Hospital / 中国药房

OBJECTIVE： To investigate the labelling problems of pediatric medication in the package inserts of skin external drugs in our hospital， and to put forward the suggestions. METHODS： A total of 46 package inserts for skin external medicine were collected from outpatient pharmacy of our hospital during Jan.-Dec. in 2018. Information on pediatric medication， precautions for pediatric medication， pediatric usage and dosage， and pediatric pharmacokinetic labelling in those package inserts was analyzed and summarized according to the types of domestic， imported and joint enterprises， classification of western medicine and Chinese patent medicine and labelling clarity， etc. RESULTS： Among 46 package inserts， 37 western medicines and 9 Chinese patent medicines were included； 31 domestic enterprises， 9 import enterprises and 6 joint ventures were involved. The ratio of pediatric medication， precautions （for pediatric medication）， pediatric usage and dosage， and pediatric pharmacokinetics labelling were 38.7％， 58.1％，  29.0％ and 0 for domestic drugs； 88.9％， 55.6％， 44.4％ and 33.3％ for imported drugs； 33.3％， 83.3％， 16.7％ and 0 for joint venture drugs； 59.5％， 62.2％， 32.4％ and 8.1％ for western medicine； 0， 55.6％， 22.2％ and 0 for Chinese patent medicine. 5 （10.9％） drug package inserts clearly indicated the usage and dosage of children； 12 （26.1％） drug package inserts were clearly labeled for the usage and dosage involving children； 12 （26.1％） drug package inserts were clearly marked to remind children to use under the supervision of doctors and adults； 11 （23.9％） drug package inserts clearly indicated that pediatric medication was not clear and the safety of pediatric medication was not yet established； 1 （2.2％） package insert clearly indicated that children should be cautious and forbidden； 3 （6.5％） package inserts did not involve package insert for pediatric medication； 2 （4.3％） package inserts clearly indicated that the drugs were stored in places not accessible to children. CONCLUSIONS： There are some problems in the package inserts of skin external drugs in our hospital， such as the marked rate of pediatric medication is quite different； the contents of the labels of pediatric medication are ambiguous and pharmacokinetic data is absent； the contents of the package inserts are inconsistent and the patients are not easy to understand professional terms. The standardization， strictness and guidance of drug package inserts for children can be improved by strengthening the supervision and management of drug package inserts by drug regulatory authorities， increasing the research and development of children’s special drugs， increasing the attention of pharmaceutical enterprises to pediatric medication， paying the attention to the revision of standard package inserts， advancing the clinical trials of children， and raising the awareness of safe drug use of patients and users.

Uso de medicamentos antidepressivos na amamentação: avaliação da conformidade das bulas com fontes bibliográficas baseadas em evidências científicas / Use of antidepressants during breastfeeding: evaluating drug package inserts conformity with science-based bibliographical sources / Uso de medicamentos antidepresivos durante la lactancia: evaluación de la conformidad de los prospectos, respecto a fuentes bibliográficas basadas en evidencias científicas

O objetivo deste artigo foi avaliar a conformidade entre as recomendações de uso de medicamentos antidepressivos durante a amamentação, presentes em bulas, e as recomendações de fontes bibliográficas baseadas em evidências científicas. Foram avaliadas as bulas padrão de 23 antidepressivos com registro ativo no Brasil. A presença de contraindicação do uso do antidepressivo durante a amamentação foi comparada com as informações presentes no manual técnico do Ministério da Saúde, no livro Medications and Mothers' Milk e nas bases de dados LactMed, Micromedex e UpToDate. Na maioria das bulas (62,5%), o antidepressivo é contraindicado na amamentação. Entre as fontes bibliográficas, esse percentual variou de 0% a 25%. O estudo aponta para baixa conformidade entre bulas e fontes bibliográficas, alertando sobre a necessidade de revisão do conteúdo e forma de apresentação das informações presentes nas bulas dos antidepressivos no Brasil.

This article sought to evaluate the conformity between recommendations regarding antidepressant use during breastfeeding found in drug package inserts with recommendations from science-based bibliographic sources. We evaluated the standard drug package inserts of 23 antidepressants with active registration in Brazil. The presence of contraindications of antidepressant use during breastfeeding was compared with information present in the Brazilian Ministry of Health technical manual, the book Medications and Mothers' Milk and on the databases LactMed, Micromedex and UpToDate. In most drug package inserts (62.5%), antidepressants are contraindicated during breastfeeding. Among bibliographical sources, that percentage varied between 0% and 25%. The study shows a low conformity between drug package inserts and bibliographical sources, alerting to the need for revising the content and presentation of information present in antidepressant drug package inserts in Brazil.

El objetivo de este artículo fue evaluar la conformidad entre las recomendaciones de uso de medicamentos antidepresivos durante la lactancia, presentes en prospectos, y las recomendaciones de fuentes bibliográficas, basadas en evidencias científicas. Se evaluaron los prospectos estándar de 23 antidepresivos con registro activo en Brasil. La presencia de contraindicaciones en el consumo de antidepresivos durante la lactancia se comparó con la información presente en el manual técnico del Ministerio de la Salud, en el libro Medications and Mothers' Milk, y en las bases de datos LactMed, Micromedex y UpToDate. En la mayoría de los prospectos (62,5%), el antidepresivo está contraindicado durante la lactancia. Entre las fuentes bibliográficas el porcentaje varió de 0% a 25%. El estudio señala la escasa conformidad entre prospectos y fuentes bibliográficas, alertando sobre la necesidad de revisión del contenido, así como de la forma de presentación de la información que aparece en los prospectos de los antidepresivos en Brasil.

Medicine package inserts from the users' perspective: are they read and understood? / Bulas de medicamentos sob a perspectiva dos usuários: elas são lidas e compreendidas?

ABSTRACT: Introduction: The written information on medicines has been acknowledged as an important tool for health education. Objective: To analyze the use and understanding of medicine package inserts by users and assess sociodemographic and medical factors associated with their comprehension. Method: Data in this analysis are part of the PNAUM National Survey - a cross-sectional population-based study conducted in Brazil. Descriptive statistics and the Pearson χ2 tests were performed to compare proportions between sociodemographic and medical characteristics, as well as use and understanding of medicine package inserts. Results: A total of 28.427 individuals responded to questions related to medicine package inserts. From these, 59.6% (95%CI 57.7 - 61.5) said they usually read the inserts, and 98.4% (95%CI 98.0 - 98.8) considered them necessary. Among people who read the medicine package inserts, more than half indicated difficulties with legibility (57.4%; 95%CI 55,2 - 59,6) and readability (54.1%; 95%CI 52.1 - 56.1). People from a lower education level reported greater difficulty in understanding them. Conclusion: The larger portion of the population usually read medicine package inserts. Nevertheless, people have difficulty in reading and understanding them.

RESUMO: Introdução: A informação escrita sobre medicamentos tem sido reconhecida como uma ferramenta importante para a educação em saúde. Objetivo: Analisar o uso e compreensão de bulas de medicamentos pelos usuários e avaliar fatores sociodemográficos e médicos associados ao seu uso e compreensão. Método: Osdados nesta análise fazem parte da PNAUM - um estudo transversal de base populacional realizado nas cinco regiões brasileiras. Estatísticas descritivas e teste de χ2 de Pearson foram utilizados para comparar proporções entre características sociodemográficas e médicas, uso e compreensão das bulas. Resultados: Um total de 28.427 indivíduos responderam a questões relativas a bulas. Desse total, 59,6% (IC95% 57,7 - 61,5) responderam que geralmente leem as bulas e 98,4% (IC95% 98,0 - 98,8) as consideraram necessárias. Entre as pessoas que leram as bulas, mais da metade indicou dificuldades de legibilidade (57,4%; IC95% 55,2 - 59,6) e de leiturabilidade (54,1%; IC95% 52,1 - 56,1) das bulas. As pessoas com menos educação relataram maior dificuldade em compreendê-las. Conclusões: A maioria da população tem o costume de ler as bulas, no entanto as pessoas consideram-nas difíceis de ler e compreender.

Analysis of package inserts of commonly used drugs in obstetrics and gynecology in Jhalawar district: an observational study in Rajasthan, India

Background: Package Insert is the primary source of drug information for the patient. It is a printed leaflet that contains information based on regulatory guidelines for the safe and effective use of a drug. Studies on package inserts in India had shown that crucial information was often missing, and they lacked uniformity.Methods: 100 oral drugs used in Obstertrics and Gynecology from different brands were collected from big pharmacies located at Jhalawar and available package inserts were analysed according to Sections 6.2 and 6.3 of Schedule D of Drugs and Cosmetics Rules, 1945.Results: Out of 100 oral drugs studied, package inserts were found in 72 drugs, most available information in therapeutic indicators was Posology and method of administration (100%) followed by contra-indications (94.4%), use in pregnancy and lactation (83%), interactions (77.8%) whereas less information about antidote and least about ability in driving and use of machine. In pharmaceutical indicators, it is instruction for use (86%), followed by special precautions for storage (76.4%), shelf life in the medical product as packaged for sale (52.8%).Conclusions: This study showed that many information relevant to the safe and effective use of medication was lacking 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.

Comparison of drug information in package inserts with standard medical textbook of pharmacology

Background: Accurate and reliable drug product information is important for the safe and effective use of medicines. But there are variations in the quantity and quality of information mentioned in different drug information sources and a single credible benchmark is lacking. This study was carried out to compare the presentation and completeness of clinical information in package inserts (PIs) marketed by pharmaceutical companies in India with standard medical textbook of pharmacology.Methods: Out of eighty five PIs of different drugs, only 55 were found eligible to be included in this study after applying inclusion and exclusion criteria. These PIs and medical textbook were analysed for quantitative and qualitative drug information and were compared using Chi square test of two proportions. The p value of 0.05 was used as cut off to evaluate statistical significance.Results: Quantitatively medical textbook was significantly better statistically in context of treatment of overdose and references. No statistically significant difference was observed in relation to information related to mechanism of action (MOA) and pharmacokinetics (Pk). After qualitative analysis, medical textbook was significantly better statistically in context of size and readability, references related to adverse drug reactions (ADRs) and indications and pictures. No statistically significant difference was observed in context of dosing interval, frequency of doses and pharmacokinetic parameters.Conclusions: PIs can be used as a reliable source of drug information by health care professionals in addition to other sources like medical textbooks.

Status of Responses to Foreign Language Inquiries When Selling OTC Drug / 医薬品情報学

Objective: Along with the increase in the number of foreign visitors to Japan, the number of inquiries in foreign languages at the time of OTC drug sales has increased.　To clarify the current status of responses to foreign language inquiries when selling OTC drug, we surveyed the frequency of foreign language response, languages used, trouble experienced, and preparation useful in responding to foreign language inquiries when selling OTC drug.Methods: Our survey was conducted with 694 registered salesclerks of drugs at an external training seminar in Tokyo, Japan.Results: Of the 649 respondents, 337 (51.9%) had experience in responding to inquiries in a foreign language when selling OTC drug.　The languages used were as follows: ”English,” 86.4%; ”Chinese,” 70.0%; ”Korean,” 25.8%.　Of the respondents who had experience in responding to inquiries in a foreign language when selling OTC drug, 107 (31.8%) responded ”I experienced trouble because I could not understand what was being said,” and 228 (67.7%) responded ”I could not respond and experienced trouble.”　When asked about preparation/tools useful for selling OTC drug, 434 (66.9%) responded ”multilingual written correspondence table,” 359 (55.3%) responded ”smartphone or tablet‐based correspondence multilingual table,” 299 (46.1%) responded ”marks and illustrations,” and 253 (39.0%) responded ”I would like to be taught how to respond in a foreign language (simple conversation).”Conclusions: Our results revealed that when selling OTC drug, response to inquiries in a foreign language occurred frequently and trouble was experienced in listening comprehension and speaking a foreign language.　Therefore, urgent countermeasures such as preparing a multilingual correspondence table of symptoms, usage, and dosage, and lectures on methods of responding through simple foreign language conversations are necessary.　In addition, efforts such as creation of multilingual drug package inserts by pharmaceutical companies were considered to be an effective measure.

Analysis on Pregnancy Contraindication in Package Inserts of Chinese Patent Medicine in Our Hospital / 中国中医药信息杂志

Objective To provide references for rational use of Chinese patent medicine (CPM). Methods The package inserts of 143 CPM which were prescribed in our hospital were set as subjects, and the contents were analyzed according to pregnancy contraindication stated in Chinese Pharmacopoeia (2015 edition). Results Among the 143 CPM, there were 74 CPM which had the contraindication labels. Only 17 CPM contained prohibited compositions and 33 CPM contained caution compositions. There were 21 CPM which had no prohibited compositions and 3 CPM had prescription confidentiality. But the contraindication labels of only 25 CPM matched with their compositions. The rest did not match with their compositions. Conclusion Some package inserts of CPM about pregnancy contraindication exist content missing and description irregularities. The drug regulatory departments should further strength the supervision and management, and improve the quality of package inserts.