A Literature-based Study On The Safety Medication Vigilance Of Traditional Chinese Medicine During Lactation

BackgroundDue to the special physiological and pathological conditions of lactating women,improper clinical medication may not only cause harm to the lactating women,but also may affect infants,so clinical medication should be used with extreme caution.Traditional Chinese medicine(TCM)has unique advantages in the treatment of breast-feeding diseases.However,currently,systematic clinical trial data on safe medication is still lacking,and the labeling of some proprietary Chinese medicines is missing or unclear.Therefore,it is urgent to carry out related researches on the medication of lactating women in clinical practice to provide some evidences for the clinical safe medication.Since the Tenth Five-Year Plan period,our research group has been performing related studies on the pharmacovigilance of TCM for about20 years.Therefore we have gradually established a ideological framework of "cognition,application,prevention and rescue of TCM toxicity" with "toxicity" serving as the core,and systematically elaborated the theory and practice of traditional pharmacovigilance of TCM.In view of the realistic background that lactation women’s traditional Chinese medicine TCM safety evidence is still lacking,this study investigated the medication risk of TCM to lactating women prescribed by medical staff in medical institutions,and excavate the understanding of the safety pharmacovigilance of Chinese medicine during lactation in ancient and modern literature.The aim is to identify the clinical medication risk of lactating women,and to refine the pharmacovigilance thought of the safe medication of TCM for lactating women.It is hoped that this study can fill the pharmacovigilance gap of the safe use of traditional Chinese medicine in lactating women and provide reference for the rational clinical application of TCM in lactation period.Objective1.Investigate the status quo of medical staffs understanding about the safe use of TCM in lactating women,and identify the potential risks of clinical lactating medication.2.Retrieve case reports of adverse reactions/adverse events(ADR/ADE)in lactating women usingTCM to clarify the characteristics and influencing factors of ADR/ADE.3.More than 70 traditional ancient books were retrieved,to establish a database of TCM pharmacovigilance thoughts during lactation period,and clarify the historical evolution of TCM pharmacovigilance thoughts in lactation period.4.In view of the risk about clinical medication,condense the pharmacovigilance thoughts on safe medication of TCM in lactation period,in order to advance the prevention of safety issues and promote rational clinical TCM use during lactation.MethodsThis research focuses on the safe use of TCM for lactating women,and combines three methods:clinical questionnaire survey,the modern literature retrieval,and the ancient literature review:1.Clinical investigation.Using questionnaire surveys,more than 500 medical staff in 29 provinces/autonomous regions/municipalities were surveyed on the cognition of the safe use of TCM in lactating women.2.The modern literature research.Following databases(January 1964-August 2020)are comprehensively and systematically searched:CNKI,Wan Fang Data,VIP,CBM and PUBMED,to collect the literatures about the ADR caused by the taking of TCM for lactating women.Then series of statistical analyses in the basic information about the patients included in the literatures,organs/systems involved in adverse reactions,clinical manifestations and outcomes,etc.are conducted.The correlations among the four characters(FC),five tastes(FT)and channel distributions of the TCM involved in ADR are analyzed by means of Apriori algorithm.3.Research on the ancient documents.73 ancient books related to safe TCM use for lactating women were systematically excavated from the Qin,Han and Ming dynasties,including monographs on obstetrics and gynecology,herbal works,prescriptions works,comprehensive works on TCM,etc.In this study,frequency statistics,percentile and association rule Apriori algorithm were adopted to establish a database of pharmacovigilance thoughts on TCM in lactation period,and to sort out the historical evolution of pharmacovigilance thoughts on TCM in lactation period.Results1.Clinical research:In this research,a total of 608 questionnaires were distributed,571 were returned,and 537 valid questionnaires were collected.The effective response rate of the questionnaire was 88.32%.The survey results showed that:(1)The interviewed medical staff did not have a satisfactory understanding of the drug safety level and the physiological and pathological pharmacokinetic characteristics of lactating women and the correct answer rate of related questions were less than 50%.(2)The interviewed medical staff lacks awareness of medication monitoring in lactating women.Approximately 35%of medical staff did not tell lactating patients to observe the baby’s reaction during medication,take health care products or food and medicine products with caution,etc.(3)The interviewed medical staff did not fully understand the safe use of TCM in lactating women.The correct rate of choosing TCM with milk-returning effects and TCM to be used with caution was less than 40%.(4)The interviewed medical staffs’s cognition about the safe use of TCM in lactating women is outdated.In addition to the drug instructions,the interviewed medical staff used books,online,and Training and other channels to obtain information about safe medication during lactating accounted for less than 36%.2.The modern literature research:In this study,the case reports of ADR/ADE caused by the application ofTCM in lactating women in the past56 yearswere collected,involving 19 single Chinese medicines,5 Chinese patent medicines,and 6 Chinese medicine prescriptions.ADR/ADE mainly affects the gastrointestinal system,skin and In its appendages,central and peripheral nervous systems,ADR/ADE occurs within 10 minutes to several days of lactating medication.The causes are individual patient differences and other biological factors,drug factors such as toxic reactions,and unreasonable medication factors such as self-administration.3.The ancient literature research:Establish a database of pharmacovigilance thoughts on TCM in lactation period.By combing the historical evolution of the pharmacovigilance thought of TCM in lactation period,the pharmacovigilance thought of TCM in lactation period in China was initially sprouted along with the proposal of the pharmacovigilance of treatment methods for postpartum diseases.Its theoretical framework was formed in the Sui and Tang Dynasties,and the content tended to be perfect in the Song,Jin and Yuan Dynasties,and was further supplemented and developed in the Ming and Qing Dynasties.4.Based on the ancientand modern literature,this research condensed the pharmacovigilance thoughts on the safe use of TCM during lactation.It mainly includes pharmacovigilance of treatment principle,reatment method,selection of TCM(Postpartum diseases,medicinal properties,dosage forms,dosages,courses of treatment,postpartum time,nursing mothers’ constitution,dietary contraindications)etc.Conclusions1.The medical staff interviewed have insufficient knowledge about the safe use of TCM during lactation period,and there are certain safety risks in clinical use of TCM.2.There are various safety problemsin the application of TCM during lactation,ranging from nausea and vomiting in lactating mothers,and rashes in infants;severe hemorrhagic shock,renal failure,permanent breast closure,and thrombocytopenia in infants.3.The traditional pharmacovigilance of TCM during lactation has rich ancient literature accumulation and theoretical connotation,which provides intuitive theoretical and data support for the condensing of pharmacovigilance thought.4.The pharmacovigilance of TCM during lactation in this research comprehensively reflects the academic characteristics of safety medication in TCM,and it also can lay the foundation for the research of clinical safe medication for lactating women and promote the clinical rational use of medication for lactating women.Innovation points1.This research use multiple methods to condense the pharmacovigilance of TCM during lactation.Based on the current situation that there is no systematic research on the safe use of TCM for lactating women,this research organically combined the clinical investigation,the modern literature and the ancient literature to summarize the pharmacovigilance of TCM during lactation.The purpose of this research is to meet the modern clinical needs of safe TCM use during lactation.2.This research systematically sorted out and explored the historical evolution and content of the traditional pharmacovigilance of TCM during lactation.This research systematically sorts out the ancient literature related to the safe TCM use of lactating women,clarifies the historical context of the evolution of the traditional medication alertness during lactation from budding to maturity to further development,and explores the pharmaco vigilance of TCM during lactation.And it provides reference and basis for the clinical use of TCM for lactating women,so as to fill the gaps in the research on the pharmacovigilance of TCM during lactation.