Bibliometric analysis of drug package insert adaptation for the elderly based on Web of Science / 中国药房

OBJECTIVE To explore the hotspots of aging adaptation of drug package inserts， and to provide evidence for the development of aging adaptation of drug package inserts in China. METHODS The relevant English literature on drug package inserts for the elderly published from 2012 to 2022 was retrieved from Web of Science Core Collection； bibliometric analysis was performed by using VOSviewer and CiteSpace software， to explore research hotspots in this field， and summarize obstacles and solutions for the development of this field. RESULTS & CONCLUSIONS This study collected a total of 335 literature related to the aging adaption of drug package inserts， from 819 research institutions in 51 countries （regions）， involving 2 174 authors. The research development of drug package insert adaptation for the elderly has slowed down in the past decade， and developed countries such as the United States and Japan dominate this field. Authors such as Wolf from Northwestern University in the United States， have the largest number of publications（12 literature）. The research focuses in this field include the risk management of medication for the elderly， the updating of medication information for the elderly in drug package inserts， and the understanding and compliance of the elderly with drug package inserts and their influencing factors. The solutions to related obstacles in the development of aging adaption in drug package inserts include improving the visibility and readability of drug package inserts， filling in the information on elderly medication in drug package inserts， and so on. China can learn from the experiences and methods of other countries， conduct investigations into the influencing factors of elderly package inserts and pharmacokinetic studies based on the characteristics of the Chinese population， and improve the safety of medication for elderly patients in multiple dimensions.

A quality audit of the medicinal package insert information of drugs marketed in India

Background: A package insert (PI) accompanying medicinal products is a concise and accessible source of evidence-based information for health professionals and consumers alike. In India, the supplied information should be adequate and fulfill the statutory regulations of the Drug and Cosmetics Rules (1945) to ensure the safe and effective drug use. Aim and Objectives: The present observational study aimed to evaluate the uniformity and adequacy of information on PIs available in India. Materials and Methods: PIs of approved and marketed drugs were collected from pharmacies and analyzed with the help of a 30-item checklist comprising of components of statutory guidelines and other quality indicators. Each item was assigned a weightage of two points if the information was complete, one if inadequate, and 0 if absent. The total score was calculated for each PI. Results: The median score of the 150 analyzed PIs was 41 (Inter quartile range, 36.00–45.25) out of a maximum value of 60. The major deficiencies observed were in providing missed dose instructions (91.33%), further reading resources (84.67%), supporting references (83.33%), and drug disposal instructions (76%). Other notable missing information were laboratory parameter interference (68.67%), clinical trial data (62%), adverse drug reaction reporting contact information (56.67%), and list of excipients (49.33%). Conclusion: There are important inadequacies in the clinical information provided in Indian PIs which can affect patient health and hinder rational drug use. Thorough evaluation and revision of the PIs is warranted to make them more reliable and popular among users.

Changes in Registration Status of Identification Codes on PMDA’s Information Search Site of Pharmaceuticals for Prescription / 医薬品情報学

The identification code of a drug is defined as “a code for identifying tablets, etc.” and is described in the “Composition/Properties” section of the package insert. We investigated whether the Pharmaceuticals and Medical Devices Agency (PMDA) website, which allows users to search package insert information, can be used for drug identification using identification codes in 2019 before the new package insert guidelines were implemented, and in 2022, during the revision period. Approximately 30% of the investigated high-risk drugs were unidentifiable in both years. The most common reason was that images were used to register identification codes on the PMDA website, and character strings were not searchable. We then conducted a questionnaire survey of pharmaceutical companies, and only approximately half of the respondents opined that it would be preferable if the registration format for identification codes was established within the pharmaceutical industry. However, hospital pharmacists urged for more simplified identification of drugs on the PMDA website.

Study of Contraceptive Duration Described in the Information Materials of Prescription Drugs Requiring Contraception / 医薬品情報学

Objective: In the instructions for package inserts (PI) of prescription drugs revised in June 2017, the section “persons with reproductive potential” was established under “precautions concerning patients with specific backgrounds.” The description rules associated with contraceptive duration were modified in these. In this study, we investigated descriptions of contraceptive duration in PI that were prepared based on the revised instructions, interview forms (IF), and other proper use materials (PM).Methods: We collected PI, IF, and PM of prescription drugs containing a new active ingredient approved from April 2017 to March 2022 for which the PI were prepared based on the revised instructions and investigated descriptions of PI, contraceptive duration, and its evidence in each information material.Results: Of the 181 drugs studied, 43.1 and 12.7% required females and males to use contraception during the period of drug consumption, respectively. Among these, the ratio of drugs that had descriptions of contraceptive duration were 15.4 and 0% for females and males at PI, respectively; 51.3 and 39.1% for female sand males at IF, respectively. Anticancer drugstended to describe contraceptive duration in the PM rather than PI or IF. For some drugs, there was no description of contraceptive duration in any of the materials. Contraceptive durations ranged from the period of administration of that drug to over a year for females and approximately one week to six months for males. The reasons for these contraceptive durations were diverse.Conclusion: Contraceptive information in the PI based on revised instructions were not sufficient for use by healthcare workers, even when the IF and PM were confirmed. These results suggest that there is a need for standardizing the descriptions, types of materials to be described, and choice of evidence for contraceptive duration.

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.

Status of package insert guidelines for drugs accessible as over the counter drugs

Background: As per Indian pharmacopoeia, package inserts are part of a label that provides information on the article. It may be the sole source of information for drugs, which are available in the pharmacies without the prescription and it may include both prescription and over the counter (OTC) drugs. So, to aid in safety and efficacy of these drugs, package inserts must follow the standard guidelines (The Drugs and Cosmetics rule, 1945). The objective of this study was to observe the status of the standard guidelines for package insert in drugs accessible as OTC drugs.Methods: Based on the inquiries made with pharmacies, list of drugs commonly bought without prescription was made. 256 drugs were evaluated. Their package inserts were observed for the extent to which the guidelines given by The Drugs and Cosmetics rule 1945, section 6.2 and 6.3 are being followed. Secondary objectives were made to assess if package inserts are physician friendly or patients friendly.Results: Package inserts were missing in 180 (70%) of the drugs. Therapeutic indications were present in 71% of the available package inserts (76). Pharmaceutical information was given in 57% of the package inserts. English was the preferred language and medicinal terms were used. Only one package insert was patient friendly.Conclusions: Package inserts should be made available in every drug. There should be a separate patient oriented package insert guideline, as per US food and drug administration (FDA), in India as well. This will aid in their safe and effective use.

Similar Drug Proposals Based on Package Inserts Using Latent Semantic Analysis / 医薬品情報学

Objective:The topic model is a well-known method used in the field of natural language processing (NLP)that defines adocument as constructed of topics that combine specific t erms. This method is used to model topic co-occurrencemathematically. In this study,we extracted topics from featu re vectors of explicit documents called medical package insertsby using cluster analysis. Methods:We counted the terms(nouns)recognized by the morphological analysis engine MeCab and created a documentterm matrix. A value of“tf・idf”was calculated in this matrix for term weighting to avoid the effect of term frequency. We reduced the dimensionality of the matrix using singular v alue decomposition,which removed unnecessary data,and weextracted feature vectors attributed to each medical package insert. The distance between feature vectors was calculatedusing cosine distance,and cluster analysis was performed based on the distance between the vectors.Results:Cluster analysis on our document-term matrix show ed that medical package inserts of drugs that have the sameefficacy or active ingredient were included in the same cl uster. Moreover, using term weighting and dimensionalityreduction,we could extract topics from medical package inserts.Conclusion:We obtained a foothold to apply our findings t o the recommendation of similar drugs. Cluster analysis ofmedical package inserts using NLP can contribute to the pro per application of drugs. In addition,our study revealed thesimilarities of drugs and suggested possibilities for new applications from several points of view.

Practice and Enlightenment of Patient Medication Guide in Foreign Countries such as Europe and America / 医药导报

Objective To study and analyze the current situation of patient medication guide in foreign countries, aiming to provide references for the preparation of patient medication guide in China. Methods The current situation of patient medication guide by consulting literatures was mastered. In addition,the design concept of patient medication guide in foreign countries was summarized, the existing problems were analyzed, and the need for improvement was discussed. Results America,Australia,European countries and some Asian countries have developed a mature patient medication guide system under the supervision of the government departments. Patient medication information overseas takes patients ' health literacy into consideration.It employs the concept of information design,focuses on risks and adverse reactions of drugs,and tells patients how to communicate with doctors and pharmacists.At the same time,it has some problems such as improper content and presentation, excessive emphasis on medication risk, not satisfying drug information demand of patients, as well as a lack of medication information for special groups such as the elderly. Conclusion The design,management and practice of patient medication guide in foreign countries set a good example for us.

Genre-based comparison of package inserts of Chinese materia medica and medicine produced in US / 中草药

The package insert is an important source of drug information which plays a critical role in guiding patients taking the medicine. Package inserts of 60 over-the-counter (OTC) oral drugs produced in the US and OTC oral traditional Chinese medicine (TCM) were collected respectively in order to compare their macrostructure and contents. The results show that there are more moves in package inserts of TCM while the contents of those US drugs are more detailed and complete. The results further deepen the understanding of package inserts as a genre and contribute to the improvement of package inserts of TCM.

Analysis of Labeled Items in Package Inserts of 51 Kinds of Ointment for External Use / 中国药房

OBJECTIVE:To provide reference for reasonably designing package inserts of ointment for manufacturers. METH-ODS:According to items included in Management Regulation for Package Insert and Label and Specification for Chemicals and Bi-ological Products for Treatment,labeled items in package inserts of 51 kinds of ointment for external use during Jan.-Jun. 2016 in our hospital were analyzed. RESULTS:Among the 51 kinds of ointment,39 were domestic varieties and 12 were imported variet-ies. In the package inserts of 39 domestic varieties,items with lower labeling rates were overdose,pharmacokinetics,use guid-ance,pharmacology and toxicology,with labeling rates of 2.6%,5.1%,15.4%,28.2%;while the labeling rates of imported vari-eties were 16.7%,83.3%,75.0%,100%. Compared with package inserts of imported ointment,composition,dosage and usage, adverse reactions,contraindications,precautions,drug interactions,medication for special populations were not enough detailed in domestic ointments. CONCLUSIONS:It is suggested that manufacturers consult medicine experts, list all auxiliary materials through Management Regulation for Drug Description and Label,refine and improve the labeling contents of dosage and usage,ad-verse reactions,precautions,medication for special populations,pharmacology and toxicology,overdose,etc. In addition,admin-istrative departments should strengthen the regulatory approval efforts.

Evaluation of Factors Influencing Addition of Clinically Significant Adverse Reactions Section in Drug Package Inserts / 医薬品情報学

<b>Objective: </b>The aim of this study was to analyze the factors influencing the addition of clinically significant adverse reactions (CSDR) section in drug package inserts in Japan.<br><b>Methods: </b>The summaries of investigation results from August 2011 to July 2014 were evaluated.  The revisions were classified into revisions based only on case reports from Japan ([Revision Y]) and revisions based on other information and/or case reports from Japan ([Revision X]).  The revisions were classified into MedDRA system organ class (SOC).  As index of amount of information from domestic case reports, the number of accumulated cases ([Case A]), cases for which a causal relationship to the product could not be ruled out ([Case B]), and fatal cases ([Case C]) were used.  In each SOC, as index of causal relationship to the product, [Index B/A] ([Case B]/[Case A]) was calculated.  Relationship of [Index B/A] to [Revision X]/all revisions, or to the number of [Case A] in [Revision Y] were evaluated.  Deference of drug lag between [Revision X] and [Revision Y] was evaluated.<br><b>Results: </b>Three hundreds twenty-three revisions with respect to the addition of CSDR section were identified.  [Revision Y] was 203 revisions (63%).  The number of [Case A], ([Case B], and ([Case C]) that were required for [Revision X] (120 revisions) were significantly lower than that were required for [Revision Y] (<i>p</i><0.0001 for all comparisons).  [Index B/A] tended to inversely correlate with [Revision X]/all revisions (<i>r</i>=−0.52, <i>p</i>=0.066), and the number of [Case A] in [Revision Y] (<i>r</i>=−0.61, <i>p</i>=0.025).  Drug lag of [Revision X] was significantly longer than that of [Revision Y] (<i>p</i><0.001).<br><b>Conclusions: </b>In future, it would especially needed to pay attention to adverse reactions with a low [Index B/A] of which revisions relatively depend on other information.

Thoughts and suggestions on the use of of chinese patent medicines in pediatrics / 中国药学杂志

OBJECTIVE: To investigate the varieties and use of oral proprietary Chinese medicines in our hospital, analyze the problems existing in their labelings, and put forward suggestions to provide reference for clinical rational drug use. METHODS: The properties of the 101 kinds of oral proprietary Chinese medicines in regard to the category, dosage form, essential drug, health care, OTC, and so on were summarized. Their labelings were collected to analyze the specification, usage and dosage, adverse reactions, contraindications and precautions, etc. RESULTS: Among the 101 traditional Chinese medicines, 44.6% were developed specially for children. When counted by categories and dosage forms, the medicines for regulating spleen and stomach and granules accounted for the majority, respectively. Essential drugs, drugs belonging to the directory of insured drugs, and OTC drugs accounted for 19.8%, 70.4%, and 26.7%, respectively. It was found that 51.5% of the labelings included dosage information for different ages in detail, 59.4% did not state adverse reactions and contraindications clearly, and the smallest dosage suggested by 14.9% of the labelings were less than the smallest packaging dose. CONCLUSION: Chinese patent medicines are widely used in pediatrics, but the information for children is still incomplete. The problems in the prescribing mainly include inappropriate selection of drugs and combination of medications. It was recommended that the relevant authorities carry out pediatric drug reevaluation and improve the labelings of pediatric drugs.

Survey analysis of the cognition of the package insert in the grassroots hospital outpatients / 药学实践杂志

Objective To understand outpatient′s attention and comprehension to package insert in the grassroots hospi-tal .Methods 608 outpatients were randomly selected to answer the questionnaires designed with relevant data .Results Pa-tients paid the highest attention to effective period ,indication ,adverse reactions and dosage in package insert with rate above 80% .The comprehension rate was low .Only three items (indication ,dosage and expiration date) were above 30% .Patient′s capability to understand package insert is related to their educational level and the area they live (urban area verse rural area ) . Conclusion Patient′s attention to package insert is high ,but comprehension level is low .We recommend that package insert should be written in the way of easy to understand for patients .Pharmacists should play an importent role in teaching patients rational drug use to ensure medication safety .

Problems and countermeasures of the package inserts for children′s anti-tumor medications in Shanghai / 药学实践杂志

Objective To review the package inserts of children′s common antineoplastic agents in Shanghai ,identify problems ,and seek countermeasures .Methods Reference summarizing and data analysis were used .Results The labeling rate of dosage for children in package inserts was only 38 .2% .There were no uniform standards for dosage modification . 70.6% of package inserts used the following ambiguous words to describe children dosage ,such as “no reliable reference” or“activity and safety are uncertain” .Only a few package inserts used words like“use with caution”or“not recommend”or“con-traindicated” .Conclusion The off-label use of children′s anti-tumor medications is unavoidable due to the limited children dos-age information in the package inserts .We recommend that hospital should have a protocol for off-label use which should be ex-amined by the ethics committee .The off-label uses and package insert standardization should be regulated by the related depart-ments in the government .Pharmaceutical manufacturers are encouraged to carry out post market research on children′s drug .

An Overview of the Package Insert and Contraindications of Filler Products in Korea / 대한피부과학회지

Filler injection is an extremely popular cosmetic procedure in Korea, but surprisingly few dermatologists are aware of the package inserts in filler products. In the era of legal dispute, it is important that we fully understand the indications, contraindications, and side effects of the individual filler products. The purpose of this paper is to provide a general overview of the contents of package inserts of filler products that are commercially available in Korea, especially in terms of the contraindications of filler injection. The authors emphasize that greater improvement in the Korean package inserts of filler products can be expected. Currently, practicing physicians are usually blamed for filler complications. We also found many significant translational errors. We hope that dermatologists take more interest in filler package inserts by reading this overview.

Analysis of Drug Use Labeling for Pregnant and Lactating Women in 762 Drug Package Inserts / 中国药房

OBJECTIVE:To provide reference for drug use labeling for pregnant and lactating women. METHODS:The drug package inserts were collected from Linxi Hospital of Kailuan General Hospital during Jul. 2013-Dec. 2015. The information about drug use labeling for pregnant and lactating women was analyzed statistically. RESULTS:Among 762 drug package inserts,pack-age inserts which were not labeled with or labeled with indefinite drug use information for pregnant and lactating women accounted for 31.89% and 52.76% respectively. Among package inserts of 361 domestic chemical drugs and biological products,339 Chinese patent medicine and 62 imported drug,package inserts which were not labeled or labeled with indefinite drug use information for pregnant and lactating women accounted for 22.99% and 25.21%,44.54% and 88.50%,14.52% and 17.74%,respectively. CON-CLUSIONS:Except for poor drug use labeling for pregnant and lactating women in package inserts package,there still are other problems,such as items listed dispersedly,presentation content not consistent. Compared with imported drugs,the missing informa-tion for pregnant and lactating women are obvious in drug package inserts of domestic chemical drugs and biological products,and severe in those of Chinese patent medicine. It is recommended that drug manufacturers should strengthen drug tracing and monitor-ing after listed,and update and revise related content of package inserts timely;drug administration department should strengthen drug package inserts supervision,and unify and standardize labeled content management of drug use.

Comparison between Risks Listed in the Risk Management Plan and the Product Labeling of the Drug Package Insert / 医薬品情報学

<b>Objective: </b>Currently, Risk Management Plans (RMPs), plan that provide new risk information about drugs, are published on the Pharmaceutical and Medical Devices Agency (PMDA) website.  The aim of this study was to compare enumerated risks in RMPs to the product labeling (PL) of the drug package insert.<br><b>Methods: </b>The risks listed in RMPs on the PMDA website were assessed on February 10, 2014.  We investigated the documentation of these risks on the PL.<br><b>Results: </b>Seven-hundred and eighty-five risks were enumerated in the RMPs of 77 drugs.  The enumerated risks were classified as “important identified risks” (66%), “important potential risks” (22%), and “important missing information” (12%).  Ninety-four percent of risks listed in RMPs were documented on the PL.  A portion of both the “important identified risks” and “important potential risks” groups were not documented on the PL.<br><b>Conclusion: </b>This study was clearly the relation between risks listed in RMPs and documents on the PL.  Because a portion of the risks listed in RMPs was not documented on the PL, RMPs provide more safety information.  It is necessary to better understanding their characteristics, considering RMPs are a new source of drug information.

Survey on off-label uses of drugs in 24 hospitals / 中国药学杂志

OBJECTIVE: To investigate the off-label uses of drugs in domestic hospitals, so as to provide baseline data for policy-making and strategy for risk management. METHODS: The off-label uses of drugs in 24 hospitals were collected and analyzed according to the categories of drugs and off-label uses and the strength of evidence for the off-label use of drugs. RESULTS: One thousand six hundred and fifty-two cases of off-label uses involving 998 drugs were included in this study. The top three hospitals with the largest numbers of off-label uses were Beijing Hospital (297 cases, 18.0%), Peking University Third Hospital (282 cases, 17.1%) and Yantai Yuhuangding Hospital (256 cases, 15.5%). There were 998 kinds of drugs which had off-label uses in these 24 hospitals. The top three categories of drugs with the highest frequncies of off-label uses were antineoplastics (388 cases, 23.5%), immunomodu-latingagents (315 cases, 19.1%), and cardiovascular system agents (177 cases, 10.7%). The off-label use of drugs concentrated in indication (1493 cases, 90.4%), dosage (349 cases, 21.1%), route and administration (154 cases, 9.3%), and population (65 cases, 3.9%) in this study. One thousand one hundred and fifty-five (73.3%) off-labels were supported by foreign package inserts, international guidelines, domestic guidelines, expert consensus, monographs and literatures. CONCLUSION: Off-label uses of drugs existed widely in these 24 hospitals, which pose potential risk on medication safety and efficacy, law responsibility and ethical issues. The government should accelerate the development and promulgation of correspondent law to promote rational use of drugs. And the relevant associations should develop guidelines for off-label uses and provide reliable evidence for safe medication.

Status Survey and Analysis on Package Inserts of Chinese Patent Drug / 中国中医药信息杂志

Objective To put forward suggestions for improving the writing standards of package inserts of Chinese patent drug in China. Methods Totally 84 package inserts of Chinese patent drug were chosen randomly. The labeled items in them would be investigated and analyzed according to legal documents in China. Results The rate of complete labeled items was 0%. Meanwhile, many problems existed in the items which affected medication safety seriously. In addition, there were defects in expression of the content, revision of package inserts of Chinese patent drug and so on. Conclusion It is urgent to improve the writing standards and the completeness of the labeled items as well as the scientificalness on the expressions of package inserts of Chinese patent drug.

Investigation and Analysis of Absent Items in Package Inserts of Common Drugs for Elderly Patients in Our Hospital / 中国药房

OBJECTIVE:To provide reference for the standardization of package insert of common drugs for elderly patients. METHODS:Outpatient prescriptions in our hospital from 2013 to 2014 were collected,and common drugs of elderly patients(≥60 years old)were ordered by consumption sum,and package inserts of top 100 drugs were statistically analyzed for absent items. RESULTS:The 100 common drugs for elderly patients included 28 Chinese traditional drugs and 72 chemical drugs. The Chinese traditional drug had more absent items,mostly were pharmacokinetics and drug overdose(92.9%),medication of elderly patients (85.7%),drug interactions(78.6%)and pharmacological actions(50.0%);the proportion of contraindications(16/28),adverse re-actions(15/28) and precaution(9/28) with uncertainty was relatively high. Items of chemicals package insert were better than Chi-nese traditional drug,absent items were pharmacokinetics and drug overdose(5.6%),medication of elderly patients and pharmaco-logical actions (2.8%) and drug interactions (1.4%);the proportion of medication of elderly patients (16/72),drug interaction and drug overdose(12/72)with uncertainty was relatively high. CONCLUSIONS:The common problem existing in the drug manu-al is characterized by absence of usage for elderly,drug descriptions is not clear,etc. Package inserts should be further improved to strengthen its standardization.