Safety Evaluation Of Tigecycline Based On FAERS And Its Effect On Coagulation Parameters

Objectives:To evaluate the safety about tigecycline based on adverse event reports of the FAERS database,then to find the risk signals and last to evaluate the meaningful risk signals through clinical research to provide an evidence for clinical medication monitoring.Methods:1.A retrospective study was conducted to analyze the adverse event reports of tigecycline as the primary suspect drug in the FAERS database from 2016 to the third quarter of 2018,and using the reported odds ratio method to mine risk signals.2.Based on the results of FAERS risk signal mining,the number of events reported by coagulopathy was high and could generate risk signals.If the coagulation disorder was not detected in time,it might lead to aggravation of the patient’s condition and threaten the patient’s life in severe cases.Coagulation disorders could be reflected by coagulation indicators,so abnormal coagulation indicators were taken as the research adverse events further.Patients admitted to our hospital from January 2016 to September 2018 treating with tigecycline were selected according to our hospital information system and the meikang rational drug use monitoring system to observe whether the coagulation parameters changed.The level of fibrinogen(FBG),prothrombin time(PT),activated partial activated prothrombin time(APTT),thrombin time(TT),platelet(PLT),white blood cells(WBC),C-reactive protein(CRP),procalcitonin(PCT),alanine aminotransferase(ALT),serum total bilirubin(TBIL),and estimated glomerular filtration rate(eGFR)were compared before and after tigecycline administration.According to whether the patients had abnormal coagulation index,Logistic regression was used to screen out high-risk factors of abnormal coagulation indicators caused by tigecycline.Results:1.Among the 227 adverse events reports of tegacycline,108(47.6%)were male,83(36.6%)were female and 36 unknown.The reporting countries mainly were the United States,China,Italy,Japan and France.The top five clinical manifestations of adverse events were drug inefficacy(n=21,4.7%),death(n=20,4.5%),shock(n=14,3.1%),acute pancreatitis(n=11,2.5%),and coagulopathy(n=10,2.2%).System organ class included were general disorders and administration site conditions(n=89,19.9%),investigations(n=58,13.0%),gastrointestinal disorders(n=54,12.1%),infections and infestations(n=51,11.4%),blood and lymphatic system disorders(n=45,10.1%).The rate of death,hospitalization or prolonged hospitalization,life threatening and disability was 57.2%.2.The effect of tigecycline on coagulation parameters was researched according toclinical study based on FARES analysis.A total of 123 eligible cases were contained in the study,including 89 males(72.4%)and 34 females(27.6%);the mean age was 57.4±18.4 years.After tigecycline was used,the FBG level was significantly lower than that before administration(P<0.05);PT,APTT and TT were significantly prolonged(P<0.05);PLT level was not significantly changed(P>0.05).At the same time,there was no significant difference in the WBC level before and after treatment(P>0.05).The difference between CRP and PCT was significantly(P<0.05).After tigecycline using,the level of WBC,CRP and PCT were lower than that before administration,it illustrated the patients’ infection status was improved.There was no significant difference in ALT level before and after medication(P>0.05),and TBIL was significantly increased(P<0.05).The difference of eGFR value before and after medication was statistically significant(P<0.05),the eGFR level was higher after administration,shown patient’s renal function improved.The median time of abnormality in FBG,PT,APTT,and TT was 6.0 days,4.0 days,5.0 days,and 6.0 days after administration.The coagulation index returned to normal or significantly improved in 4.0 days(1-12 days)after discontinuation of the drug.Logistic analysis found that high dose of tigecycline use was a risk factor for abnormal coagulation parameters(P<0.05,OR=2.825,95% CI 1.274-6.266).Conclusions:1.The adverse events of tigecycline are closely related to its therapeutic effect,which should be used in a standard and reasonable way;in addition to efficacy-related adverse events,coagulopathy is an important factor in tigecycline-induced adverse events,more attention should be pay on coagulation disorder caused by tigecycline.2.Tigecycline can cause FBG decline,PT,APTT,TT prolonged,and should pay more attention on the FBG and the APTT.3.Patients who used tigecycline had abnormal coagulation indicators within 1 week,and coagulation indicators could return to normal levels or improve significantly after one week of discontinuation.It is found that the coagulation abnormality caused by tigecycline can be discontinued the drug first.4.Tigecycline doses higher than 150 mg per day are risk factors that lead to abnormal coagulation parameters.