Data Analysis of the Risks of Abnormal Female Reproductive System Haemorrhages Induced by Novel Oral An- ticoagulants Based on FAERS / 中国药房

OBJECTIVE：To eva luate the risk of abno rmal female reproductive system haemorrhage induced by novel oral anticoagulants （NOACs）. METHODS ：The abnormal female reproductive system haemorrhage reports induced by 4 kinds of NOACs as “dabigatran etexilate ”，“rivaroxaban”，“apixaban”and“edoxaban”were used as the first suspected dugs to collected from FDA adverse event reporting system （FAERS）database during Jan. 1st，2004-May 31st，2019. The report odd ratio （ROR） method was used to detect the signal of abnormal female reproductive system haemorrhage induced by NOACs. RESULTS ：A total of 2 658 adverse events related to abnormal female reproductive system haemorrhage were collected from FAERS database ， involving 330 reports of dabigatran etexilate ，2 049 reports of rivaroxaban ，267 reports of apixaban ，and 12 reports of edoxaban. The abnormal female reproductive system haemorrhage caused by dabigatran etexilate ，apixaban and edoxaban mainly occurred in patients aged 75 and older ，accounting for 37.27％，36.70％ and 58.33％ respectively；that of rivaroxaban mainly occurred in patients with 45-64 years old ，accounting for 33.04％. The incidence of severe adverse events （SAE）induced by dabigatran etexilate，rivaroxaban，apixaban and edoxaban were 96.36％，84.53％，47.19％ and 58.33％，respectively. All of patients in the included reports were mainly hospitalized and hospitalization stay wa s prolonged ，accounting for 64.78％，90.01％，86.51％ and 71.43％ ，respectively. A total of 12 suspected signals were detected，involving cervix uteri ，fallopian tube ，ovary，pelvis cavity，uterus，vagina，urinary tract ，etc. Among them ，there were 11 positive signals of rivaroxaban ，and the bleeding events were concentrated in vaginal hematoma [ROR ＝12.07， 药。95％CI（8.51，17.12）]，postmenopausal hemorrhage [ROR ＝ 9.89，95％CI（8.31，11.77）]，pelvic hematoma [ROR ＝7.68，95％CI（5.66，10.43）]. There were 4，4 and 2 suspicious signals for dabigatran etexilate ，apixaban and edoxaban. The main bleeding events of both apixaban [ ROR＝5.18，95％CI（1.81，5.85）] and edoxaban [ROR ＝48.19，95％CI（6.76，343.77）] were vaginal hematoma ；dabigatran etexilate-induced pelvic hematoma [ROR ＝ 12.56，95％CI（8.92，17.70）] had the strongest signal ，followed by urinary tract bleeding [ROR ＝5.41，95％CI（3.34，8.76）] and pelvic hemorrhage [ ROR＝2.53，95％CI（1.88，3.40）]. CONCLUSIONS ：Totally 4 kinds of NOACs can cause abnormal female reproductive system haemorrhage ，and the incidence of SAE is high ，of requiring hospitalization or prolonging hospitalization time. The risk of haemorrhage in rivaroxaban is the highest ，usually manifesting as vaginal hematoma ，postmenopausal hemorrhage and pelvic hematoma. Dabigatran etexilate mainly induce pelvic hematoma ，while apixaban and edoxaban are mainly cause vaginal hematoma.

Literature Analysis of 118 Cases of Propylthiouracil-associated Small Vasculitis / 中国药房

OBJECTIVE:To investigate the general regularity and characteristics of propylthiouracil (PTU)-associated small vasculitis (ASV),and to provide reference for rational drug use in the clinic. METHODS:ADR/ADE case reports of PTU-ASV published during 1990-2016 were retrieved. The data of 118 ADR cases were analyzed statistically. RESULTS:The incidence of PTU-ASV was higher in female and was highest in 18-59 age group. Drug dose of 87 patients were within 600 mg/d,and the inci-dence of PTU-ASV was the highest within 1-5 years after medication. Main clinical manifestations were renal and lung function in-jury. After drug withdrawal,59 patients received hormone therapy,and 30 patients received hormone combined immunosuppressive agent. Finally,115 patients were recovered and 3 patients died. CONCLUSIONS:In older to reduce or avoid the occurrence of ADR,it is necessary to regularly check antineutrophil cytoplasmic antibody related indexes and evaluate the symptoms of ADR.

Excavation and Evaluation of Security Alert Signals of Linezolid Based on Reporting Odds Ratio Method / 中国药房

OBJECTIVE:To excavate and evaluate the security alert signals of linezolid after marketing,and to provide refer-ence for rational drug use in clinic. METHODS:The reporting odds ratio(ROR)method was used to excavate the security alert signals from the adverse drug events(ADE)data in the OpenFDA platform of FDA during second quarter of 2004-2016. The low-er limit of 95%CI >1 was regarded as suggestive of ADE alert signal. RESULTS:A total of 6828534 reports were extracted, among which there were 7224 reports mainly induced by linezolid. Top 10 ADE reports were thrombocytopenia,drug interac-tion,thrombocytopenia,nausea,anaemia,serotonin syndrome,diarrhoea,pyrexia,drug ineffective,vomiting. After the detec-tion of top 200 ADE reports by ROR method,120 signals related to 18 system organ class(SOC)were identified. Top 5 ADE sig-nals in turn by SOC were medical examination,nervous system disorders,blood and lymphatic system disorders,metabolism and nutrition disorders,cardiac disorders. The high risk signals with clinical reference value included 42 cases of optic neuropathy (ROR=56.33),350 cases of serotonin syndrome(ROR=52.86),162 cases of lactic acidosis(ROR=18.30),31 cases of endo-carditis (ROR=15.38),566 cases of thrombocytopenia (ROR=14.29),122 cases of bone marrow failure (ROR=14.20),261 cases of panhematopenia (ROR=11.92),86 cases of disseminated intravascular coagulation (ROR=10.91),58 cases of toxic epidermal necrolysis(ROR=9.06),etc. As for ADE reports,male was slightly higher than female,and the patients in age group of ≥45 reported evidently more compared to younger age group. CONCLUSIONS:By detecting and evaluating alert signals of li-nezolid through OpenFDA platform,we could effectively lay the foundation for further research of pharmacovigilance.