| Purpose:The project is to evaluate the safety of xiyanping injection(XYP)through systematically searching the literature databases and the SRS data.The potential medication risks can be obtained,and the next step is to improve the medicine specification in order to guide a more normative application of XYP.The research method is expected to be a guide of conducting a comprehensive post-marketing safety evaluation of other traditional Chinese medicine inj ections.Methods:In the first and second parts,seven medical databases including Pubmed,Embase,Cochrane,CNKI,WanFang,VIP and CBM were searched from inception to January 2018.The search terms were andrographolide sulfonate and xiyanping.Case reports and clinical trials detailing ADRs/AEs associated with XYP were included.Data were extracted independently by two reviewers.After the assessment of causality and severity,we carried out a descriptive analysis for the relevant ADRs/AEs.The third part was retrieved from SRS of National Adverse Reaction Monitoring Center during January 1,2004 to August 31,2017.The suspected ADRs of XYP in the clinical application were analysed across the country.The fourth part was based on all the notice and announcements from National Medical Products Administration in 2015-2019 and was combined with the recommendations above the three sections.According to the data information and the evidence,the medicine specification of XYP can be improved programmatically and used for a better clinical application.Results:In the first part,forty-three articles involving a total number of 55 cases were included.Eight cases were off-label drug use.In the remaining 47 cases,26(55.3%)had probable causality and 23(48.9%)were serious cases.XYP used in children(?14 years old)accounted for 66.0%.Among 15 cases under 4 years old,nine were serions cases.Respiratory diseases(83.0%)were major primary diseases.No allergic history mentioned(55.3%)and unspecific drug combination(59.6%)were common in these reports.No drug mixed were reported as well.The regular combinations were antibiotics and antiviral drugs.As for ADR types,anaphylaxis and anaphylactic shock were up to 97.9%.ADRs happened mostly when applying XYP within 30 minutes(70.2%)and the majority(95.7%)were cured when treated in time.In the second part,263 articles involving a total number of 971 patients were included.There were 1161 symptom cases in the 971 included AEs.The year distribution of the articles was largely in 2015 and the main provinces were in Guangdong,Henan and Jiangsu.Hand-foot-mouth disease of children,upper respiratory tract infection,pneumonia and bronchiolitis in children and psoriasis in adult were main primary diseases.XYP used in children accounted for 76.42%.Only 1 patient of 971 mentioned the allergic history.The course of XYP treatment was reported mainly in 7 days.The regular combinations were azithromycin,ribavirin and avium A capsule and no drug mixed were reported.The relevant off-label drug use contained improper application of dosage,dripping speeding,frequency,menstruum and administration methods.The relevant cases of AEs were large in diarrhea,rash,nausea,vomiting and itching.Among all the AEs,63.34%had not collected the occurrence time,55.61%had not provided the treatment for AEs and 54.79%had not informed the prognosis.In the third part of SRS in 2014-2017,the incidence of suspected ADRs in every year and every age group was in a rare level(0.01%-0.1%).Moreover,the incidence of suspected severe ADRs in every year and every age group was in a very rare level(<0.01%).The ADR types were mainly rash,itching and other skin system diseases.Relevant ADRs defined for certain,probable and possible causalities reached for more than 90%of all the cases.In the fourth part,on basis of the 2016 XYP instruction,"functions" can be updated for treating bronchitis,tonsillitis,bacterial dysentery,hand foot and mouth disease,psoriasis and other excess heat syndromes."Dosage"was advised within 7 days and shall not exceed 4 hours after adding the solvent."ADRs" should add the cases of anaphylactic shock,anaphylactoid reaction,rash,ecchymosis,cold extremities,scratchy throat,stuffy nose,urinary system(the case report of scrotal edemaand hypouria),etc."Contraindication" can be updated for the prohibition when patients were allergic to the andrographis preparations and XYP,and it was also forbidden to apply XYP for patiens in allergic constitution.It was recommended to change the prohibition for children under the age of 1 to children under the age of 4.As for the "announcement",it should be taken notice of the combination of azithromycin,penicillin,cephalosporin antibiotics,ribavirin and avium A capsule,etc.It should also notice the exclusion of improper administration methods such as aerosol inhalation.Conclusion:Clinical application should obey the medicine specification and take notice of the usage,the dosage,proper dripping speeding,frequency,menstruum and administration methods.The application of children should be strictly distinguished from the adults,and attention should be paid to the interval between flushing tube and medication.More evidence should be provided on the effectiveness and safety of other applications(such as hand foot and mouth disease,psoriasis,etc.)in order to avoid the use of widely infectious diseases without the practical evidence.The patients with allergy history and allergic constitution shall be collected and forbidden to use XYP.Meanwhile,intensive monitoring shall be conducted within 30 minutes after the beginning of the medication.The quality of safety reports in clinical trials should be improved and the causality should be evaluated to avoid the mislead between the AE and XYP due to the improper drug use,the progression of diseases,the drug combinations and other factors.While the incidence of ADRs in XYP was low,the mechanism of its allergic reaction and anaphylactoid reaction still needs to be strengthened in order to use XYP in a scientific and reasonable way.By improving the medicine specification,it can better guide the application of safe drug-use and minimize the drug risk. |
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