Objective To explore the occurrence and risk factors of piperacillin sodium and tazobactam sodium (TZP)-related hypokalemia.　Methods The clinical data of adult inpatients treated with TZP in Linyi Central Hospital from January 2022 to January 2023 were collected through the hospital′s electronic medical record system, including patient demographic information, infection sites, major underlying diseases, laboratory tests, TZP use information and concomitant drugs, and patients with TZP-related hypokalemia were screened. The occurrence of TZP-related hypokalemia was analyzed by descriptive statistics. According to whether or not having TZP-related hypokalemia, the patients were divided into hypokalemia group and non-hypokalemia group, and the clinical characteristics were compared. The clinical characteristics with statistically significant differences between 2 groups were included in the multivariate logistic regression, and the risk factors of TZP-related hypokalemia were analyzed.　Results A total of 363 patients were included in the analysis, of which 86 (23.7%) were with hypokalemia and were judged to be associated with TZP, 46 (53.5%) were male and 40 (46.5%) were female; the age was 76 (68, 83) years. Of the 86 patients, 76 (88.4%) had mild hypokalemia, 10 (11.6%) had moderate hypokalemia, and none had severe hypokalemia. Through clinical characteristic comparison between the hypokalemia group and the non-hypokalemia group, statistically significant differences were found in patient gender, age, body mass index, the proportion of patients with pulmonary infection, abdominal/gastrointestinal infection, and urinary tract infection, the proportion of patients with coronary atherosclerotic heart disease and without major underlying diseases, baseline hemoglobin, serum total protein, serum albumin, blood calcium, blood magnesium, and the proportion of patients using potassium preserving diuretics and other diuretics during TZP treatment (all P<0.05). The above variables were included in the multivariate logistic regression, and the results showed that only the baseline level of blood magnesium was an independent influencing factor of TZP-related hypokalemia, and the lower the level, the higher the risk (odds ratio=0.105，95% confidence interval: 0.012-0.956，P=0.045).　Conclusions Hypokalemia is a common adverse reaction of TZP, which should be paid attention to in clinic. The lower level of blood magnesium at baseline may be related to the increased risk of hypokalemia during TZP treatment.

A 78-year-old female patient with type 2 diabetes for 30 years, hypertension for more than 10 years, diabetes nephropathy for 4 years, and renal anemia for several years additionally received roxadustat (70 mg thrice per week orally) for anemia. After 5 days, the patient developed sudden chest tightness, asthma, acute left heart failure, and depressed edema of both lower limbs. The electrocardiogram showed sinus arrest, escape rhythm, and a heart rate of 40 beats per minute. Laboratory test results showed   blood  pH 7.31， blood potassium 5.3 mmol/L, blood creatinine 304 μmol/L, B-type natriuretic peptide 1 280.0 ng/L, high sensitivity troponin T 0.042 μg/L, and creatine kinase MB 0.83 μg/L. Acute left heart failure, hyperkalemia, and metabolic acidosis caused by roxadustat were considered. Roxadustat and other long-term oral medication such as hypoglycemic and antihypertensive drugs were discontinued. Symptomatic treatments such as sodium bicarbonate, insulin, furosemide, calcium gluconate, and blood filtration were given. Two days later,the patient′s heart rate and blood potassium returned to normal; 7 days later, the patient′s B-type natriuretic peptide was 168.0 ng/L, blood creatinine was 170 μmol/L, and blood potassium was 4.13 mmol/L. The patient had no chest tightness or asthma, and no edema in both lower limbs. Long-term oral medication such as hypoglycemic and antihypertensive drugs were given again. At a 1 month follow-up, the patient did not experience chest tightness or asthma, and the electrolyte levels were normal.

Anticancer drugs are important causes of kidney injury in cancer patients. Once kidney injury occurs, it will affect anticancer therapy and patient prognosis. Thus, the Japanese Society of Nephro- logy, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made a particular discussion on the prevention and management of anticancer drug-induced kidney injury. This article focuses on interpreting the management of kidney injury related to cytotoxic anticancer drugs, targeted therapies, and immune checkpoint inhibi-tors to more effectively guide clinical practice.

In 2023, a total of 27 742 cases of medication error (ME) from 439 hospitals in 27 pro‑vincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medica‑tion. Among them, 282 (1.02%) were classified as grade A, 22 452 (80.93%) as grade B, 4 239 (15.28%) asgrade C, 499 (1.80%) as grade D, 141 (0.51%) as grade E, 127 (0.46%) as grade F, 1 (<0.01%) as grade G,and 1 (<0.01%) as grade I; no MEs of grade H occurred. Among the 27 460 patients involved in MEs ofgrade B to I, 15 131 (55.10%) were male and 12 329 (44.23%) were female; their ages were from 1 day to103 years; 3 198 (11.65%) were children (<18 years old), 12 576 (45.80%) were young and middle‑agedadults (≥18 to <60 years old), and 11 686 (42.56%) were elderly (≥60 years old). The top 3 contents of MEwere wrong drug class (5 880 cases, 20.97%), wrong dosage (4 668 cases, 16.65%), and wrong administration·390·药物不良反应杂志 2024 年7月第 26 卷第7期 ADRJ，July 2024, Vol. 26, No. 7frequency (3 184 cases, 11.35%). A total of 270 patients were involved in severe MEs (grade E‑I), including140 (51.85%) males and 130 (48.15%) females, aged from 52 days to 94 years, of which 31 (11.48%) werechildren, 91 (33.70%) were young and middle‑aged adults, and 148 (54.82%) were elderly. The top 3 drugsinvolved were cefoperazone sodium and sulbactam sodium, metformin, and estazolam. One fatal ME wascaused by mistakenly orally taking Fufang Jingjie for fumigation and washing. Among the 27 460 gradeB‑I MEs, 19 655 (71.58%) were triggered by physicians, 5 688 (20.71%) by pharmacists, and few by nurses,patients and their family members, etc. These MEs mainly occurred in clinics (10 537 cases, 38.37%), inhospital wards (8 187 cases, 29.81%), and in pharmacies (6 470 cases, 23.56%). But among the 270 severeMEs, 121 (44.81%) occurred in the patient′s home. The top 3 persons who discovered the ME were phar‑macists (20 693 cases, 74.46%), patients and their family members (3 240 cases, 11.66%), and physicians(2 214 cases, 7.97%). The top 3 factors causing ME were lack of related pharmacologic knowledge (9 382cases, 28.3%), tiredness (5 974 cases, 18.05%), and insufficient training of medical workers (3 831 cases,11.58%). In view of MEs with high incidence or more severe in 2023, relevant risks should be paid attentionto, including misusing external drugs for internal use, ingestion of drug packaging by mistake, wrong doseconversion in children, ME in special dosing frequency, too fast infusion speed of enteral nutrition prepara‑tions and irritant intravenous preparations, interaction between montmorillonite powder and other drugs,hypernatremia caused by fosfomycin sodium, etc. In addition, strengthening the management of drug varietieswith frequent severe MEs and fatal MEs, as well as the popular science and safe drug use education forpatients, can help ensure the medication safety of patients.

A 31-year-old woman received semaglutide injection subcutaneously for weight loss. Three months later, the electrocardiogram showed sinus tachycardia, and the laboratory tests showed triiodothyronine (T3) 2.75-nmol/L, thyroxine (T4) 199.86-nmol/L, free triiodothyronine (FT3) 11.31-pmol/L, free thyroxine (FT4) 46.63-pmol/L, thyroid-stimulating hormone (TSH)<0.005 mU/L. Considering the sinus tachycardia and hyperthyroidism caused by semaglutide injection, the drug was discontinued, and methimazole 10-mg orally, twice daily and metoprolol 25-mg orally twice daily were given. After treatment for more than 1 month, the electrocardiogram of the patient was normal, and the thyroid function examination showed T3-1.79-nmol/L, T4-127.33-nmol/L, FT3-4.94-pmol/L, FT4-15.87-pmol/L, and TSH<0.005 mU/L. However, there were elevated liver enzymes, showing alanine aminotransferase 327-U/L, aspartate aminotransferase 148-U/L, and γ-glutamyl transpeptidase 123.4-U/L. Then, methimazole and metoprolol were stopped, and silibinin 140-mg orally thrice daily combined with bicyclol 50-mg thrice daily were given. More than 1 month after treatments, the patient′s thyroid function and liver function were normal, and silibinin and bicyclol were stopped. After that, the thyroid function, liver function and electrocardiogram were all normal in repeated examinations.

Objective To mine the adverse events (AE) risk signal of azithromycin in children, establish the corresponding pharmaceutical care process, and provide reference for the safe use of azithromycin in clinic.　Methods AE caused by azithromycin in children (<18 years) were searched from the US FDA Adverse Event Reporting System (FAERS) database from the 1st quarter of 2004 to the 4th quarter of 2023. The AE was standardized and classified using the preferred term (PT) and system organ class (SOC) in the Medical Dictionary for Regulatory Activities 26.1 version. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used for detection of AE signal of azithromycin. AE that simultaneously met the following conditions was considered as a risk signal: the number of reports≥3, lower limit of the 95% confidence interval of ROR≥1, PRR>2, and χ2>4. Descriptive analysis on the signals was performed. The pharmaceutical care process of azithromycin for children was established based on the results of signal mining and satisfaction survey was conducted.　Results A total of 1 457 AE reports related to azithromycin in children were collected, involving 127 PTs and 18 SOCs. The top 5 PTs in the number of reports were rash, pruritus, urticaria, drug hypersensitivity and diarrhea. The top 5 PTs in signal intensity were infantile diarrhea, myasthenia gravis crisis, intermittent explosive disorder, diarrhea neonatal, and infantile vomiting. A total of 16 risk signals that were not recorded in the label were mined out, and the top 5 PTs according to signal intensity were intermittent explosive disorder, conversion disorder, bronchiectasis, tooth discoloration, and choreoathetosis. The analysis of 79 AE reports with death outcomes showed that drug-induced liver injury, Stevens-Johnson syndrome, rash, vomiting, nausea, cyanosis, and diarrhea were related risk signals. Based on the signal mining results mentioned above, the medication safety officer team in our hospital established a pharmaceutical care process of azithromycin application for children, including pre-medication assessment (indications, medical history, heart and liver function, etc.), speed and mode of administration monitoring during the medication, and intervention measures after the occurrence of adverse reactions, and 178 hospitalized children who received azithromycin treatment were monitored. The satisfaction survey results showed the degree of satisfaction was 100%.　Conclusions The main AEs related to azithromycin in children are rash, pruritus, urticaria, drug hypersensitivity, and diarrhea, all of which are recorded in the label. In addition, we should also be vigilant against the risk signals such as intermittent explosive disorder, conversion disorder, bronchiectasis, tooth discoloration, and choreoathetosis, which are not recorded in the label. The pharmaceutical care process for azithromycin use in children based on the risk signal mining results is feasible and effective.

Accumulation of drugs and its metabolites in the body occurs and risks of adverse drugreactions increase in renal insufficiency patients due to the renal function decline or delay of renal excretionand the pharmacokinetic changes related to the decline of renal function. Therefore, the dose of anticancerdrugs should be adjusted in tumor patients with renal dysfunction. The Japanese Society of Nephrology,JapanSociety of Clinical Oncology,Japanese Society ofMedical Oncology,and Japanese Society of Nephrologyand Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and specifically discusses the dose adjustment of anticancer drug forpatients with renal injury in the second chapter. This article focuses on the interpretation of the principle ofdrug dose adjustment for patients with renal insufficiency and suggestions for dose adjustment of platinumdrugs and fluorouracil drugs in this chapter.

Due to the characteristics of cytotoxicity, vascular toxicity, and immunotoxicity, anticancer drugs may be more likely to cause kidney injury than other drugs. It is an important content in anti  tumor treatment to fully understand the clinical manifestations and risk factors of anticancer drug related renal injury, and evaluate the disease severity reasonably, so as to better adjust the anticancer schedule. Thus, the Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made special discussions and suggestions on the definition, evaluation methods, main clinical manifestations, and risk factors of drug induced kidney injury in cancer patients after receiving anticancer drug treatments. This article interprets this part of the content in order to make more effective guidance in clinical practice.

With the aging of the population and the increasing number of patients with throm- boembolic diseases, oral anticoagulants are more and more widely used. Anticoagulant-related nephropathy (ARN) is a significant adverse reaction in the treatment with oral anticoagulants, generally considered to be a form of acute kidney injury caused by excessive anticoagulation. The mechanisms involved may include glomerular hemorrhage, obstruction of renal tubules by red cell casts, and damage to tubular epithelial cells. Abnormalities in coagulation function and renal function are the main risk factors for ARN; older age, diabetes mellitus, and cardiovascular diseases such as hypertension and heart failure also increase the  risk of ARN occurrence. ARN should be managed based on individual patient characteristics. Benefits and risks of treatment should be carefully considered when choosing oral anticoagulants; renal function should be closely monitored during treatments to detect potential risks early. In case of ARN, it is advised to promptly adjust the anticoagulant therapy and provide symptomatic supportive treatments. In severe cases, treatments with methylprednisolone combined with hemodialysis can be employed.

The safety of traditional Chinese Medicine (TCM) has garnered widespread attention and has become a major obstacle to its further development and internationalization. The complexity of TCM and the unpredictability of its interactions with the human body pose significant challenges to safety research. The causes of TCM safety issues are multifaceted, including intrinsic and extrinsic toxicity, confusion of herbal sources and misuse in clinical practice, inadequate patient awareness of safe medication use, and insufficient regulatory oversight of TCM quality and safety. To strengthen the risk managements, it is essential to employ scientific technologies to investigate the fundamental nature of TCM safety, leverage artificial intelligence for big data analysis and early risk warning, promote the scientific concept of safe TCM use, and establish a comprehensive lifecycle pharmacovigilance system for TCM. These will facilitate TCM safety research in China, ensure patient medication safety, and promote the healthy and sustainable development of the TCM industry and its internationalization.

Intravenous infusion has played an important role in emergency treatments in China, but there is also the phenomenon that emergency infusion is overused. The high burden of emergency infusion may cause more medication safety problems, such as adverse drug reactions, medication errors, drug interactions, and so on. The risks in emergency infusion should be paid high attention to. We should actively construct a comprehensive management model for the prevention and control of emergency infusion safety risks by strengthening multidisciplinary cooperation, avoid unnecessary intravenous infusion, and develop diagnostic criteria and treatment guidelines for adverse events in intravenous infusion, so as to better ensure the medication safety in emergency patients treated with intravenous infusion.

Objective To understand the occurrence of drug?drug interaction (DDI) in medical orders and the relevant common medications of hospitalized patients treated with voriconazole.　Methods The treatment information of hospitalized patients treated with voriconazole and had blood trough concentration (Cmin) results in Quanzhou First Hospital, Fujian Province from May 2018 to August 2023 was collected through the hospital information system. Descriptive statistical analysis was conducted on the incidence of DDI medical orders, the drugs involved in DDI, the types and risk levels of DDI, the departments where DDI occurred, and the Cmin changes of voriconazole in patients with 1 or 2 type of voriconazole?related DDI medical orders (including drugs not recommended in combination with voriconazole or voriconazole dose needs to be adjusted when combined) during voriconazole treatment.　Results A total of 752 patients were included, of which 592 (78.7%) had 1?344 medical orders with voriconazole?related DDI, involving 28 drugs. Among them, 67.7% (401/592) of patients used 2 or more DDI drugs. Glucocorticoids ［91.6% (542/592)］, followed by proton pump inhibitors ［87.8% (520/592)］, were most frequently involved in the medical orders of DDI with voriconazole. Among the 28 voriconazole?related DDI drugs, 5 were involved in type 1 or 2 DDI, including rifampicin, nirmatrelvir/ritonavir, phenobarbital, phenytoin sodium, and rifabutin. The 5 drugs involved 33 patients, of whom 51.5% (17 patients) had voriconazole Cmin<1.0?mg/L; rifampicin involved the most patients (17 patients), followed by nirmatrelvir/ritonavir (10 patients). When voriconazole was combined with rifampicin, rifabutin, phenobarbital and phenytoin sodium, its Cmin in most patients decreased significantly. The incidence of medical orders with voriconazole?related DDI was highest in the Intensive Care Unit, followed by the Department of Respiratory and Critical Care Medicine.　Conclusions Medical orders with DDI are very common in the clinical application of voricona- zole, and most patients have used two or more DDI drugs, in which glucocorticoids and proton pump inhibitors appeared more common. It is necessary to be alert to the occurrence of DDI between voriconazole and rifampicin, rifabutin, phenobarbital and phenytoin  sodium in clinic.

Antineoplastic agents; Acute kidney injury; Renal insufficiency; Guideline; Interpretation

Objective To analyze the occurrence and clinical features of liver injury induced by dandelion, a food-medicine homologous traditional Chinese medicine.　Methods The patients with liver injury caused by taking dandelion, who were admitted to the Department of Infectious Diseases, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 1, 2017 to December 31, 2023, were enrolled in this study. The electronic medical records of the patients were retrieved, and the patients′ general information, using of dandelion, combined medication, clinical manifestations, and liver biochemical test results were recorded. The causal relationship between dandelion and the liver injury were evaluated, and the clinical manifestations, classification, severity, treatment and prognosis of liver injury were analyzed.　Results A total of 13 patients were enrolled in the study, including 8 females and 5 males. The age ranged from 29 to 78 years. Nine patients took dandelion by themselves, and 4 accor- ding to the doctor′s advice. The administration methods included dandelion root tea drink, whole herb tea drink, and powder drink mixed in water. Most patients′ liver injury occurred within 90 days after taking dandelion. The main clinical manifestations were yellowish staining of skin and sclera, dark urine, abdominal distension, abdominal pain, loss of appetite, etc. The laboratory tests showed that serum aminotransferase and bilirubin increased in 13 patients, alkaline phosphatase increased in 12 patients, and plasma ammonia increased in 5 patients. The causality evaluation results showed "probable related" in 8 cases and "highly probable related" in 5 cases. The clinical classification showed that 11 patients were of hepatocellular type and 2 of mixed type. The severity was mainly grade 2 (8 of 13 patients). Two patients with grade 3 and 2 patients with grade 4 developed liver failure. After symptomatic treatments, 11 patients′ liver function returned to normal or were improved; 2 patients′ condition progressed, of which 1 patient survived after liver transplantation and 1 patient died.　Conclusions Dandelion can cause liver injury, mostly occurring within 90 days after administration, with moderate severity. After stopping dandelion and giving symptomatic treatments, most patients have a good prognosis, but there is a risk of liver failure and death.

Objective To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.　Methods The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals ［ROR method: ≥3 reports  and the lower limit of the 95% confidence interval (CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed.　Results A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1-888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort (ROR=28.87, PRR=28.85), injection site discomfort (ROR=24.48, PRR=24.40), sinus pain (ROR=23.20, PRR=23.19), injection site vesicles (ROR=17.63, PRR=17.61), and injection site rash (ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity.　Conclusion The main AE  of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

Objective To actively monitor and analyze the safety of levofloxacin and sodium chloride injection produced by Guangzhou Green Cross Pharmaceutical Co., Ltd (generic drug). and levofloxacin and sodium chloride injection produced by Daiichi Sankyo (Beijing) Pharmaceutical Co., Ltd (original drug).　Methods The data in this study came from the adverse drug reaction reports on levofloxacin and sodium chloride injection voluntarily monitored and reported to the National Adverse Drug Reaction Monitoring System Database by the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial People′s Hospital, and the First Affiliated Hospital of Ji'nan University from October 1, 2022, to September 30, 2023. The information on patients′ age, gender, medication use, primary disease, time from medication to the occurrence of adverse reactions, clinical manifestations, treatment and prognosis of adverse reactions, and the occurrence of serious adverse reactions were collected. The incidence of adverse reactions was calculated.　Results A total of 30 adverse reaction reports involving levofloxacin and sodium chloride injection were collected, involving 30 patients. In the generic drug group, there were 21 cases, including 8 males and 13 females, aged from 20 to 91 years with a median age of 43 years; 2 cases of serious adverse reactions were reported. In the original drug group, there were 9 cases, including 3 males and 6 females, aged from 20 to 96 years with a median age of 56 years; no serious adverse reactions were reported. In the generic drug group, a total of 36 adverse reactions occurred in 21 patients, while in the original drug group, a total of 13 adverse reactions occurred in 9 patients. These adverse reactions involved the skin and appendages, digestive system, nervous system, musculoskeletal system, urinary system, and medication site, with skin itching and rash being the most common allergic reactions (15 case time in the generic drug group, accounting for 41.7%; 6 case time in the original drug group, accounting for 46.2%). Two cases of serious adverse reactions occurred in the generic drug group, and both were anaphylactic shock. After discontinuation of the drug, switching to other antibiotics, and symptomatic treatments, 5 cases in the generic drug group were cured, 15 cases were improved, and 1 case was unknown. In the original research drug group, 2 cases were cured and 7 cases were improved. There were no deaths in either the generic or original drug groups. The incidence of adverse reactions in outpatients and/or inpatients in the generic drug group was 0.07% (21/29 557), while that in the original research drug group was 0.08% (9/10 686). There was no statistically significant difference between the 2 groups (χ2=0.183, P=0.669).　Conclusion The results of active monitoring show that there is no significant difference in safety between the generic and original drugs of levofloxacin and sodium chloride injection.

Anti-microbial agents are one of the most widely used drugs in clinical practice, with a high incidence of adverse drug reactions, and the safety problem is very prominent. There are many factors that affect the occurrence, development and severity of adverse reactions caused by anti-bacterial agents. The research on the related risk factors is one of the measures to ensure the safety and effectiveness of anti-  infection treatment, and it is also the premise of preventing and identifying adverse reactions caused by anti-bacterial agents. This paper summarizes and evaluates the research hotspots and methods on common adverse reactions risk factors for anti-bacterial agents, and puts forward relevant suggestions according to the problems and deficiencies existing in the current research status, with the aim of promoting research on adverse reactions-related risk factors for anti-bacterial drugs in China and ensure the safety of patients′ medi-cation.

Objective To analyze the clinical characteristics and treatments of adverse reactions and anaphylaxis induced by cisatracurium besylate, and provide reference for medication safety in clinic.　Methods Adverse reaction reports of cisatracurium besylate in database of Shandong Provincial Center for Adverse Drug Reaction Monitoring between January 1， 2008 and April 18， 2023 were collected and analyzed retrospectively. The adverse reaction terminology was standardized using the preferred terms and system organ class (SOC) in the Medical Dictionary for Regulatory Activities 25.1. The cases of anaphylaxis were selected and graded. The characteristics of all anaphylaxis and treatments of anaphylaxis of grade Ⅱ-Ⅳ were analyzed.　Results A total of 163 adverse reaction reports were included for analysis, involving 201 preferred terms. The top 3 SOCs involved were mainly skin and subcutaneous tissue disorders (133 cases， 66.17%), vascular disorders (14 cases, 6.96%), and immune system disorders(14 cases, 6.96%). One hundred and forty-five patients (89.0%) experienced anaphylaxis, mainly within 10 minutes after medication (115 cases, 79.3%). Of them, 37 (25.5%) patients had anaphylaxis of grade Ⅱ-Ⅳ. The most common initial symptom was circulation system symptoms (19 cases， 51.4%), followed by skin or mucosal signs (12 cases, 32.4%). The main therapeutic drugs included glucocorticoids (27 cases, 73.0%), adrenaline (17 cases, 45.9%), and other vasopressors other than adrenaline (19 cases, 51.4%). All patients showed improvement or recovery in symptoms after treatments.　Conclusions The anaphylaxis caused by cisatracurium besylate mainly occurred within 10 minutes after medication and have a good prognosis. For anaphylaxis classified as grade Ⅱ-Ⅳ, the acute phase treatment drugs mainly include glucocorticoids, adrenaline, and other vasopressors other than adrenaline.

Intravitreal injection (IVI) is an administration technique that uses a syringe to deliver drugs into the vitreous cavity. Currently, multiple IVI drugs have been successively approved for the treatment of various fundus diseases, including antivascular endothelial growth factor drugs, intravitreal sustained- release glucocorticoid drugs, and so on. Meanwhile, there are many injection drugs off label used by IVI. At present, there is a lack of pharmaceutical care guidance documents for the clinical application of IVI drugs. To promote the development of pharmaceutical care for IVI drugs, Ophthalmic Pharmacy Professional Committee of Peking Safety Medicine Foundation, Medicine Therapy Management Working Committee of Chinese Pharmacists Association, and Clinical Pharmacy Branch of China International Exchange and Promotive Association for Medical and Health Care organized experts to formulate this consensus based on clinical practice experience and with reference to relevant domestic and foreign research data, guidelines, and literature. This consensus combs the characteristics of clinical application of IVI drugs, relevant pharmaceutical services before, during and after injection, and forms 26 recommendations for 5 clinical issues, which can be used by medical institutions at all levels to carry out pharmaceutical services of IVI drugs. The users are medical staff in medical institutions at all levels (including pharmacists, physicians, nurses, and other relevant staff), and the target population for application is mainly patients using IVI drugs.

A 66-year-old female patient with multiple chronic diseases was on long-term treat- ment with digoxin, spironolactone, metoprolol, atorvastatin, dapagliflozin, and entecavir, with no abnormality platelet count (PLT). Due to hypertrophic obstructive cardiomyopathy and atrial fibrillation, digoxin was discontinued, and rivaroxaban 15 mg once daily orally was added to prevent thrombosis. Concurrently, furosemide, sacubitril valsartan, meglumine adenosine cyclophosphate, and silibinin was given for cardiac load reducement, blood pressure control and heart failure improvement, myocardial nutrition, and liver function improvement, respectively. After the initiation of this regimen, the patient′s PLT gradually decreased and was 51×10⁹/L on day 13. Drug-induced thrombocytopenia was considered, with rivaroxaban being the likely causative agent. Rivaroxaban was then switched to warfarin, methylprednisolone 40 mg was administered intravenously once, and the remaining medications were continued. The patient′s PLT gra- dually increased. On day 11 after discontinuing rivaroxaban, the PLT was 155×10⁹/L. At a 2-week follow- up, PLT of the patient was 169×10⁹/L.

Objective To understand the pre-warnings of contraindicated drugs in medical advices in patients with renal insufficiency by the pre-audit system.　Methods The pre-warnings of contraindicated drugs in medical advices in patients with renal insufficiency by the pre-audit system in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 1, 2021 to December 31, 2021 were collected. The drugs involved were analyzed and determined as drugs in the correct pre- warnings and drugs in the audit rules that needed to be corrected. The drugs involved in the correct pre- warnings and the acceptance of pre-warnings by clinicians were analyzed; drugs that can be used off-label according to the evidence-based information were recorded and the proposed suggestions on the revision of the audit rules were provided.　Results A total of 259 medical advices about pre-warnings related to contraindicated drugs in patients with renal insufficiency were included in the analysis, involving 47 drugs. Among the 259 pre-warnings, 169 were correct, with the correct rate of 65.25%, and 107 (63.31%) of them were accepted by clinicians. The rate of acceptance by surgeons was higher than that by physicians, and the difference was statistically significant ［76.39% (55/72) vs. 53.61% (52/97), P<0.01］. The audit rules in the 90 pre-warnings that needed to be modified involved 12 drugs. Of them, one drug (dapagliflozin tablets) had updated instruction, thus the rules can be modified directly according to it. The other 11 drugs were recorded for off-label drug use in the system based on evidence-based information, and of them, pre-warning levels were adjusted for 6 drugs, and audit rules were adjusted for 5.　Conclusions The pre-audit system can effectively pre-warning the contraindicated drug prescriptions of CKD patients, and the correct rate of pre-warning and clinician acceptance rate are more than 60%. The audit rules of some pre-warnings need to be adjusted with the update of the instructions and additional evidence-based information for off- label drug use after recording.

Objective To explore the influencing factors of coagulation disorders caused by cefoperazone sodium and sulbactam sodium in patients with chronic renal insufficiency.　Methods The medical records of adult patients with chronic renal insufficiency, who were hospitalized and treated with cefoperazone sodium and sulbactam sodium in the Department of Nephrology of the Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People′s Hospital from January 2021 to December 2022, were collected. Patients who developed coagulation disorders related to cefoperazone sodium and sulbactam sodium were imputed as having an end-point event, and the occurrence of end-point events in these patients was analyzed descriptively. According to whether an end-point event occurred, patients were divided into end-point event group and non-end point event group. Univariate and multivariate logistic regression analysis were performed on the risk of end-point events.　Results A total of 121 patients with renal insufficiency were included in the analysis, including 76 males (62.8%) and 45 females (37.2%), aged (66±13) years. Among 121 patients, 39 (32.2%) had end-point events, and 6 (5.0%) had clinical bleeding. The results of univariate analysis showed that the differences in age, renal replacement therapy, and daily and total doses of cefoperazone sodium and sulbactam sodium of patients between 2 groups were statistically significant (all P<0.05). Multivariate logistic regression analysis was performed using the occurrence of end-point events as dependent variables, and age, renal replacement therapy, and daily and total doses of cefoperazone sodium and sulbactam sodium as independent variables. The results showed that only older age was an independent risk factor for the occurrence of end-point events (odds ratio=1.044, 95% confidence interval: 1.004-1.086, P=0.029).　Conclusions Patients with renal insufficiency have a higher risk of coagulation disorders in treatment with cefoperazone sodium and sulbactam sodium, and older age is an independent risk factor. Cefoperazone sodium and sulbactam sodium should be used cautiously in elder patients, and coagulation function monitoring should be strengthened in clinical use.

The "Top 10 drug tips for the public in 2023" issued by the Chinese Pharmaceutical Association emphasizes the importance of drinking water correctly to the safety and efficacy of drugs. Each drug has an optimal amount of drinking water, and only the appropriate amount can ensure the efficacy and avoid adverse reactions. According to UpToDate clinical consultant, Micromedex, MCDEX evidence-based databases and the drug labels of the US FDA and the European Medicines Agency, a total of 164 drugs in 20 categories, including drugs for metabolism and endocrine system, anti-infective drugs, anti-tumor drugs, etc., were labeled with the recommendation of adequate water intake. Here we summarize the above-mentioned drugs and their recommended water intake. The common reasons to drink enough water include preventing esophageal and gastric injury, preventing kidney injury, preventing dehydration, water and electrolyte disorders, preventing constipation, reducing bladder toxicity, reducing radiation damage, and promoting stone discharge. In addition, different people have different requirements for the amount of water when taking medicine. Mastering the correct amount of water is conducive to controlling the disease and reducing the adverse drug events.

Objective To analyze the influencing factors on the occurrence of acute kidney injury(AKI) in hospitalized patients treated with esomeprazole and to construct a risk prediction model to predictthe occurrence of esomeprazole‑associated AKI. Methods The study was designed as a retrospectivestudy. The subjects were selected from patients who were hospitalized in the First Affiliated Hospital of·405·药物不良反应杂志 2024 年7月第 26 卷第7期 ADRJ，July 2024, Vol. 26, No. 7Shandong First Medical University from January 2018 to December 2020 and received treatment withesomeprazole. The clinical data of patients, including basic information, operations, intervention measures,medication, and laboratory test results, was collected through the hospital′s electronic medical recordsystem. Patients were divided into AKI and non‑AKI groups according to the occurrence of esomeprazole‑associated AKI, and the clinical characteristics between the 2 groups were compared. The least absoluteshrinkage and selection operator (LASSO regression) was used to analyze the influencing factors ofesomeprazole‑associated AKI. Patients were randomly divided into the training set and the test set at a 8∶2ratio. Based on data in the training set, 5 machine learning algorithms were used to build esomeprazole‑asso‑ciated AKI prediction models, including logistic regression, random forest, gradient boosting machine(GBM), extreme gradient boosting, and light gradient boosting machine. Based on data in the test set, the per‑formance of 5 models was validated through the area under the receiver operating characteristic curve (AUC),sensitivity, specificity, and accuracy. Results A total of 5 436 patients were enrolled in the study, including 3 231 males and 2 205 females, with an age of 61(51, 70) years. Esomeprazole‑associated AKI occurredin 393 patients, with an incidence of 7.23%. The results of LASSO regression analysis identified 24 variablesclosely related to esomeprazole‑associated, such as hepatic insufficiency, chronic renal insufficiency, hypo‑proteinemia. Based on data in the training set (4 349 patients), the esomeprazole‑associated AKI risk predic‑tion models were constructed and their predictive performance was good (all AUC>0.900). The predictiveperformance validation was conducted using the data in the test set (1 087 patients), and the results showedthat the GBM model has the highest AUC (0.922) and relatively stable performance, with small differences invarious indicators between the training and the test sets. Conclusions The use of esomeprazole is signifi‑cantly associated with AKI, and the risk is influenced by factors such as baseline renal function, comorbidi‑ties, and combined medications. The risk prediction model based on GBM algorithm is helpful for earlyassessment of the risk of esomeprazole‑related AKI in clinical practice.

Anticancer drugs play an important role in the treatment for malignant tumors. The kidney function of patients has an important impact on the choice of anticancer drugs, the safety during treatments, and the prognosis of patients. All cancer patients should undergo comprehensive kidney function assessment before using anticancer drugs, so as to formulate an individualized anticancer regimen. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made special discussions and suggestions on the evaluation of kidney function of tumor patients before anticancer drug treatment. This article interprets this part in order to made a more comprehensive understanding on the occurrence and risk factors of kidney disease in cancer patients in the clinic. Paying attention to the kidney function assessment of cancer patients before anticancer drug treatment and mastering the correct assessment methods can help improve the kidney safety of cancer patients during treatments.

Pre-marketing clinical trials may fail to detect rare or delayed adverse drug reactions (ADRs) due to insufficient sample size and short follow-up periods. Therefore, continuous post-marketing safety evaluation is necessary. Evidence generation relies on discovering ADR signals and conducting studies to verify specific risks. Integrating evidence from multiple sources through methods like meta-analysis can further enhance the comprehensiveness and reliability of drug safety evaluations. Additionally, risk management in clinical practice should be emphasized by developing standardized clinical guidelines and establishing decision support systems to facilitate the dissemination and application of evidence, ensuring its practical use. Constructing an evidence ecosystem not only helps identify and understand potential medication safety issues, but also enhance the scientific and practical aspects of risk management, ultimately reducing patient harm from ADRs.

Objective To explore the clinical characteristics of cardiotoxicity due to 5-hydroxytryptamine 3 receptor (5-HT3) antagonists.　Methods Relevant databases at home and abroad (up to June 20, 2023) were searched and case literature of cardiotoxicity induced by 5-HT3 receptor antagonist were collected. Relevant information of patients, medication status (drug name, usage and dosage, indication, combined drugs), occurrence of cardiotoxicity, evaluation of the association between 5-HT3 receptor antagonists and cardiotoxicity, intervention measures and outcomes were extracted and analyzed descriptively and statistically.　Results A total of 23 case reports, 22 in English and 1 in Chinese, were enrolled in the analysis. There were 26 patients, 6 males and 20 females, and the age ranged from 8 to 60 years, with an average of 40 years. The reasons for drug use were perioperative antiemesis in 19 patients, chemotherapy antiemesis in 2 patients, and other reasons in 5 patients. Ondansetron was used in 19 patients, dolasetron in 4 patients, granisetron, tropisetron and palonosetron in 1 patient each. Except for 1 patient with overdose by self-medication, the dosage in 25 patients was within the recommended range in labels. A total of 50 case time of cardiotoxicity occurred in 26 patients, mainly including tachycardia (12 cases), electrocardiogram (ECC) changes (11 cases), bradycardia (9 cases), cardiac arrest (1 case), and myocardial infarction (1 case), etc. Twenty-one patients experienced cardiotoxicity after initial medication, of which 8 occurred immedia- tely after the initial medication, 5 patients occurred after ≥2 times of medication. After the occurrence of cardiotoxicity, 26 patients stopped 5-HT3 receptor antagonists successively, of which 24-stopped the drug immedia- tely and received symptomatic treatments, 1 stopped the drug after 8 days of medication without other intervention, and 1 stopped the drug and received symptomatic treatment after the symptoms aggravated. After drug withdrawal and/or symptomatic treatments, the mentioned symptoms disappeared and ECC returned to normal in 25 patients. Of them, 22 patients had a recovery time of ≤48-hours, while the other 3 patients had their ECG returned to normal at 1 week, 2 weeks, and 2 months, respectively; one patient died due to ineffective treatment for ventricular fibrillation.　Conclusions The cardiotoxicity induced by 5-HT3 receptor antagonists mostly occurs after the initial medication, and mainly manifests as tachycardia, bradycardia, ECG changes, etc. Most patients have a good prognosis after timely drug withdrawal and symptomatic treatments, and in severe cases, it can lead to death.

Objective To investigate the differences in the incidence of QT interval prolongationbetween moxifloxacin and levofloxacin in anti‑infective therapy among cardiology intensive care unit (CCU)patients, and to analyze the risk factors for QT interval prolongation. Methods The data of patients whoreceived anti‑infective treatments with moxifloxacin and levofloxacin in CCU of Xiaogan Central Hospitalfrom January 2020 to December 2022 were collected and analyzed retrospectively. The clinical characteris‑tics in the 2 groups were compared. Potential influencing factors of QT interval prolongation were analyzedusing univariate regression analysis. Variables with P<0.2 were included in a logistic regression model formultivariate analysis. The effect values were expressed as odds ratio (OR) and its 95% confidence interval(CI). Results A total of 146 patients were included in the study, with 76 patients in the moxifloxacingroup and 70 patients in the levofloxacin group. In the moxifloxacin group, 18 out of 76 patients (23.68%)experienced QT interval prolongation, while in the levofloxacin group, 6 out of 70 patients (8.57%) experi‑enced QT interval prolongation; the difference between the 2 groups was statistically significant (P=0.025).There were no statistically significant differences in other factors between the 2 groups. Univariate regression·412·药物不良反应杂志 2024 年7月第 26 卷第7期 ADRJ，July 2024, Vol. 26, No. 7analysis showed that female (OR=2.958, 95%CI: 1.144-7.647, P=0.025), myocardial infarction (OR=2.958,95%CI: 1.144-7.647, P=0.025), concomitant use of amiodarone (OR=2.569, 95%CI: 1.042-6.337, P=0.040)and escitalopram were influencing factors of QT interval prolongation. Factors with P<0.2 were entered inthe multivariate logistic regression analysis, and the results showed that female (OR=3.616, 95%CI:1.240-10.538, P=0.019), hypokalemia (OR=2.953, 95%CI: 1.263-6.905, P=0.012), and myocardial infarc‑tion (OR=3.026, 95%CI: 1.057-8.666, P=0.039) were independent risk factors for QT interval prolongation.Conclusions Moxifloxacin is associated with a higher incidence of QT interval prolongation compared tolevofloxacin. Female and patients with hypokalemia and myocardial infarction have high risks for QT intervalprolongation.

Chronic kidney disease (CKD) has become a global public health problem. Slowing disease progression is vital in CKD management, and drug therapy is an important part of the treatment for CKD patients. However, the risk for adverse drug event is higher in patients with CKD due to impaired renal function, prolonged disease duration, presence of multimorbidity and polypharmacy. Therefore, it was recommended to promote medication safety in patients with CKD through the following 4 specific strategies: (1) carrying out more studies to improve evidence-based practice for medication in patients with CKD; (2) conducting dose adjustments according to glomerular filtration rate and continuous drug therapy monitoring to a dynamic management of the dose; (3) implementing multidisciplinary care； （4） utilizing appropriate information technology actively.

Objective To mine the risk signal of acute kidney injury (AKI) induced by different oral anticoagulant drugs (OACs) in various populations and provide a reference for clinical use of OACs.　　Methods Reports of AKI induced by OACs and non-OACs in the US Food and Drug Administration Adverse Event Reporting System database from the 1st quarter of 2004 to the 3rd quarter of 2023 were collected. The relationship between the drugs mentioned above and the AKI in patients were analyzed by methods of reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). When the number of reports of the target adverse event (AE) for the target drug was ≥3, and the lower limit of the 95% confidence interval (CI) of ROR was >1 or the lower limit of the 95%CI of the information component (IC025) was >0, it indicated a statistically significant association between the target drug and the target AE.　Results A total of 12 402 AKI reports related to OACs were collected, including 1 313 for warfarin, 3 086 for dabigatran, 4 730 for rivaroxaban, 2 918 for apixaban, and 365 for edoxaban; 454 378 AKI reports were related to non-OACs. The overall analysis of OACs showed an ROR (lower limit of 95%CI) of 1.791 (1.759) and an IC (IC025) of 0.813 (0.787) for AKI caused by OACs. Analysis of individual OACs showed that warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban all posed risks for AKI, with ROR (lower limit of 95%CI) of 1.220（1.156）, 2.386（2.302）, 2.044（1.986）, 1.375（1.326）, 3.003（2.706）, respectively, and IC (IC025) of 0.284（0.204）, 1.231（1.178）, 1.010（0.968）, 0.452（0.399）, 1.560（1.407）, respectively. Edoxaban had the highest ROR and IC values, while warfarin had the lowest. Subgroup analysis showed that in the <18 years subgroup, neither warfarin nor rivaroxaban showed a risk of AKI; the ROR method did not show dabigatran to have a risk of AKI, but the BCPNN method did. In the 18-45 years subgroup, both methods showed that apixaban did not have a risk of AKI, while all other OACs did. In the 45-64 years subgroup, all OACs showed a risk of AKI. In the ≥65 years subgroup, warfarin and apixaban posed risks for AKI. Gender subgroup analysis showed that both methods indicated a risk of AKI with warfarin in males; all OACs showed a risk of AKI in females.　Conclusions OAC has a statistically significant risk of AKI, among which edoxaban has the highest risk intensity and warfarin has the lowest. Different OACs have different risks of AKI in patients with different ages.

Objective To explore the status and problems of safety recommendations in clinical practice guidelines and expert consensuses (guidelines/consensuses) on Chinese patent medicine (CPM) in China.　Methods Wanfang Med Online, CNKI, VIP, China Biology Medicine Database, Chinese Medical Journal Full Text Database, and the websites of Medlive, and China Association of Chinese Medicine were searched, and the guidelines/consensuses related to CPM were collected. The basic information, types, subject areas, evidence rating methods, safety reporting items, safety recommendation levels, and evidence sources of these guidelines/consensuses were extracted and analyzed by descriptive statistics.　Results A total of 138 guidelines/consensuses were included in the analysis, including 19 guidelines and 119 consensuses. The first guideline/consensus on CPM was published in 2004. Five, 3, 9, 15, 29, 32, 29, and 11 guidelines/consensuses were published respectively from 2016 to 2023. From 2020 to 2023, 101 guidelines/consensuses were published, which was 2.73 times the total number of those published in the past 16 years.(101/37). Among the 138 guidelines/consensuses, 59 (42.75%) were "disease?based" and 79 (57.25%) were "drug?based". The top 5 institutions in terms of the number of publications were National Administration of Traditional Chinese Medicine, China Association of Chinese Medicine, Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences, Chinese Association of Integrative Medicine, and Chinese Medical Association, of which National Administration of Traditional Chinese Medicine issued 19 guidelines. However, the issuing units of 26 guidelines/consensuses were medical colleges/medical institutions and the issuing units of 8 guildlines/consensuses were not clearly stated. Among the 138 guidelines/consensuses, 18 (13.04%) did not describe the safety of drugs and 120 (86.96%) described. Among the 120 guidelines/consensuses, none of the safety recommendations were graded according to The Grading of Recommendations Assessment, Development and Evaluation, and only 32.50% (39/120) of the evidence sources contained randomized controlled trials. A proportion of 50.72% (70/138) in 138 guidelines/consensuses did not report the funding situation, and 37.68% (52/138) did not disclose the conflict of interest.　Conclusions In recent years, the number of guidelines/consensuses on CPM has increased significantly in China, but the issuing agencies of some of them had poor authority. Most of the guidelines/consensuses are "drug-based", the descriptions of safety are insufficient, the evidence level is low, and there may be some bias.

With the spread of hemodialysis therapy and the continuous breakthrough of kidney transplantation technology, the survival period of patients with end stage renal disease is prolonged, and malignant tumor has become one of the main causes for hospitalization and death of patients on hemodialysis and undergoing kidney transplantation. Due to the particularity of pharmacokinetics in patients on dialysis and the long term maintenance immunosuppressive therapy in kidney transplant patients, many aspects need to be considered and balanced in these patients when they need anti tumor drug treatments. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and systematically answers many clinical questions about anticancer drug therapy in patients on hemodialysis and underwent kidney transplantation in the second chapter. This article interprets this part to provide references for the anti-tumor drug treatments of patients on dialysis and after kidney transplantation in China.

A 67-year-old male patient with intrahepatic bile duct carcinoma was treated with oxaliplatin (hepatic artery perfusion)+gemcitabine (hepatic artery perfusion)+camrelizumab (intravenous infusion)+apatinib (oral). Platelet count (PLT) decline (49×109/L) was observed after 2 months (apatinib had been discontinued by himself), which was improved after platelet elevating therapy. Due to multiple tumor metastases, bevacizumab (hepatic arterial perfusion, once per 30 days) was added. Before bevacizumab treatment, PLT and coagulation function of the patient were basically no abnormalities. After 2 cycles of treatments, the PLT was 101×109/L and prothrombin time was 14.1 s. Considering the high risk of bleeding in interventional therapy, oxaliplatin and gemcitabine were discontinued, and bevacizumab administration was changed to intravenous infusion. PLT and coagulation function were not improved. Six days after the 5th dose of bevacizumab, the patient had intermittent hematemesis twice (about 300 ml). Laboratory tests showed PLT 75×109/L and prothrombin time 15.8 s. The patient was diagnosed with digestive tract hemorrhage. Fasting and water restriction was performed, and gastric acid suppression, hemostasis, parenteral nutrition, etc. were given. The patient had no hematemesis but intermittent black stool. Gastroscopy indicated duodenal ulcer accompanied by bleeding. Rabeprazole and sucralfate were added. Fasting was stopped and liquid diet was given. The next day, the patient had blood in the stool, and the bleeding of the lower digestive tract was judged to be related to camrelizumab and bevacizumab. The bleeding symptoms were slightly improved after treatments with arterial embolization hemostasis and type A cryopprecipitation coagulation factor, etc. Later， the patient had repeated bleeding condition, and finally died despite of rescue efforts.

Objective To explore the risk factors of severe medication errors (ME) of tranexamic acid injection (TXAI), and put forward prevention suggestions.　Methods TXAI-related ME reports in the National Monitoring Network for Clinical Safe Medication (Monitoring Network) and medical literature databases at home and abroad were searched, and case reports of TXAI-related ME were collected; China Judgements Online and PKULAW database were searched, and TXAI-related judicial cases judged to be responsible by the hospital were collected. The retrieval time of all data was up to May 1, 2024. The severity grade, occurrence link and place, and the trigger person of TXAI-related ME reported in the Monitoring Network were retrospectively analyzed. The year of report, country of occurrence, clinical application, error content, and occurrence place of the collected severe ME cases, and the clinical characteristics of patient injury, patient outcome and the ME grading were retrospectively analyzed.　Results From September 22, 2012 to May 1, 2024, the Monitoring Network received a total of 138 TXAI-related ME reports, and there was an increasing trend in the number of reports year by year. Among 138 cases of ME, 79 (57.3%) occurred in the drug dispensing and distribution link; 58 (42.0%) occurred in the prescription/doctor′s order prescribing and delivery link and mainly involved easily mixed drugs and drug overdose, of which 1 (1.7%) was a severe ME (grade E); 1 (0.7%) occurred in the drug administration link, and iodohexol was mistakenly injected as TXAI into the patient′s joint cavity. A total of 29 severe ME reports related to TXAI were collected. Of them, 24 (82.8%) were due to incorrect administration routes (22 were confused with anesthetics and 2 were confused with injection catheters, all resulting in incorrect intrathecal injections) and 5 (17.2%) were due to prescription errors (3 were overdosed, 1 was used for high-risk thrombosis patient, and 1 was treated with combination use of hemocoagulase for high-risk thrombosis patient); 23 (79.3%) occurred in the operating rooms, and 6 (20.7%) occurred in the wards. The 24 patients involved in incorrect intrathecal injections of TXAI mainly developed severe pain, neurotoxicity (status epilepticus) and/or cardiotoxicity (arrhythmia and ventricular fibrillation), of which 11 (45.8%) died and 2 (8.3%) had sequelae of limb muscle weakness. Among the 5 patients with prescription errors, 4 developed severe thrombotic disease, resulting in 2 deaths and 2 cerebrovascular-related sequelae, and the other one developed palpitation, shortness of breath, nausea and vomiting. Among the 29-severe ME cases, 2 (6.9%) were grade E, 3 (10.3%) were grade F, 4 (13.8%) were grade G, 7 (24.2%) were grade H, and 13 (44.8%) were grade I.　Conclusions TXAI-related ME mainly involved easily mixed drugs and prescription errors. The severe ME main occurred in the operating room and mainly due to incorrect intrathecal injection, leading to fatal neurological and cardiac toxicity in patients.

Objective To mine the adverse events (AE) of nervous system caused by epidermal growth factor receptor (EGFR) inhibitors, and provide reference for the safe use of EGFR inhibitors in clinics.　Methods AE of nervous system caused by gefitinib, erlotinib, afatinib and osimertinib were searched from FDA Adverse Drug Event Reporting System (FAERS) database using OpenVigil data platform from 2004, 2004, 2013, and 2015 to the 2nd quarter of 2023, respectively. The AE was standardized using the preferred term (PT) in the Medical Dictionary for Regulatory Activities 23.0 version. Data such as patient general condition and AE of nervous system was extracted from AE reports and was analyzed descriptively. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used for detection of AE signal of nervous system. AE that simultaneously met the following conditions was considered as a risk signal: the number of report cases ≥3, lower limit of the 95% confidence interval of ROR≥1, PRR≥2, and χ2≥4.　Results A total of 422 nervous system AE cases related to gifitinib were collected, involving 297 patients and 42 preferred terms (PT); 10 risk signals were detected, including dementia, brain oedema, demyelina- tion, leukoencephalopathy, hemiplegia, vocal cord paralysis, neurological symptom, cerebral atrophy, intracranial pressure increase and neuropathy, with 64 AE cases involved. One thousand seven hundred and fifty?five nervous system AE cases related to erlotinib were collected, involving 1?477 patients and 69 PT; 7 risk signals were detected, including ageusia, hyperaesthesia, facial pain, demyelination, motion sickness, vocal cord paralysis, peripheral paralysis, with 142 AE cases involved. Two hundred and forty?seven nervous system AE cases related to afatinib were collected, involving 212 patients and 32 PT; 7 risk signals were detected, including ageusia, cerebral infarction, brain oedema, epilepsy, central nervous system lesion, leukoencephalopathy, cerebral disorder, with 49 AE cases involved. Six hundred and fifty?two nervous system AE cases related to osimertinib were collected, involving 582 patients and 46 PT; 3 risk signals were detected, including cerebral infarction, vocal cord paralysis, facial paralysis, with 54 AE cases involved. Ageusia was an AE already included in the label of afatinib, while other AE were not included.　Conclusion Most of the EGFR inhibitor?related AE signals found in the FAERS database are not included in the labels, and should be monitored during the clinical use.

Objective To explore the clinical characteristics of adverse reactions induced by levofloxacin in the emergency infusion unit.　Methods The study was designed as a single center prospective cohort study. Data of adverse drug reaction (ADR) in the Infusion Unit of Emergency Medicine Center of First Affiliated Hospital of Nanjing Medical University was managed, recorded and collected according to the pre-formulated "emergency infusion unit drug adverse reaction management process" and "strengthening the reporting of observational studies in epidemiology (STROBE)". The incidence, severity, clinical characteristics, intervention measures, outcomes, and follow-up of adverse reactions induced by levofloxacin from November 2019 to October 2022 was summarized and analyzed.　Results A total of 426 cases of ADR occurred within the set time period, of which 62 (14.55%) were related to levofloxacin, involving 27 males (43.55%) and 35 females (56.45%) with a median age of 39 years. Among the 62 levofloxacin-related ADRs, 96.77% (60/62) occurred within 2 hours of intravenous infusion of levofloxacin; the severity of 44 (70.97%), 10 (16.13%) and 8 (12.90%) cases of ADRs was classified as grade 1, 2, and 3, respectively, and no grade 4 ADRs occurred. The most common clinical symptoms were skin and mucosa reactions, including rash and itching, followed by cardiovascular system and nervous system manifestations, including hypotension, palpitation, and dizziness. The skin and mucosa manifestations were more common in patients with severity grade 1 ADRs, while the cardiovascular, digestive, respiratory nervous system and systemic manifestations were more common in those with severity grade 2 and 3 ADRs; the differences were statistically significant (all P<0.05). After the occurrence of ADRs, levofloxacin was withdrawn in all the 62 patients, the infusion set was replaced, and infusion of 0.9% sodium chloride injection were used to flush the tube. Additionally, 24 patients (38.71%) were given drug intervention, including epinephrine in 2 patients. After the above intervention, the symptoms of all patients were relieved, with a median response time of 49-minutes.　Conclusions Levofloxacin was one of the common drugs causing ADR in the emergency infusion unit. The clinical manifestations were mainly rashes and itching, most of which were mild in severity. Timely disconti- nuation of levofloxacin and drug interventions often help get a good prognosis. However, the treatment procedure of severe ADRs remain to be standardized.

A 64-year-old female patient received treatments such as antibacterial, analgesic, etc. due to local swelling and blisters caused by application of domestically made drug for external use for knee joint pain. After 7 days, local skin redness and swelling appeared, with scattered rashes. Anti-allergic treatments including intravenous infusion of calcium gluconate and oral desloratadine cirate were given. On the second day, the patient developed a wheal like rash all over her body, and intravenous infusion of anti-allergic drugs were continued. On the same day, the patient′s skin symptoms were improved. The patient′s systemic rash worsened again after 1.5-hours of reapplication of desloratadine cirate, and the next day, angioneurotic edema appeared. Desloratadine cirate was stopped, dexamethasone, promethazine, and other symptomatic treatments were continued. Four days later, the patient′s symptoms completely disap- peared.

Objective To investigate the reasons for contraindication of chemical drugs and biological products that were marked as contraindication for children in drug labels in China.　Methods The drugs labeled as contraindication for children in drug labels of chemicals and biological products covered by the China Pharmacopoeia 2020 and the 2023 China′s Basic Medical Insurance, Work?related Injury Insurance and Childbirth Insurance (western medicine) were searched. The reasons of contraindication for children were collected through searching the drug labels, Clinical Medication Instructions of the China Pharmacopoeia 2020, the website of the National Medical Products Administration, and drug labels from the Unite States, and analyzed descriptively.　Results There were 222 drugs were labeled as contraindication for children in the drug labels, involving 20 categories and mainly antibiotics and digestive system drugs. Among 222 drugs, 137(61.7%) had the reasons for contraindication in pediatric patients, and the main reasons were adverse drug reactions (65.7%, 90/137) and lack of effectiveness and safety information yet in children (30.7%, 42/137), followed by the unsafe auxiliary materials (1.5%, 2/137), unsuitable pres- cription design or ingredients for children (1.5%, 2/137) and unsuitable dosage form for children (0.7%, 1/137). The above reasons were collected from domestic drug instructions (100 drugs), U.S. drug labels (17 drugs), NMPA website instructions revision announcements and popular science knowledge (15 drugs), and Clinical Medication Instructions of the China Pharmacopoeia 2020 (5 drugs).　Conclusions It is relatively common in China to label drugs that are contraindicated for children without specifying the reasons for contraindication or with non?standard explanations in the instructions. Therefore, it is necessary to further standardize the contraindication information for children and apply continuous updates and improvement in order to provide timely and up?to?date drug use information for clinical practice.

A 67-year-old male patient received long-term use of benidipine (8 mg once daily orally) and allisartan isoproxil (240-mg once daily orally) due to hypertension. Her blood pressure was controlled at around 150/80-mmHg. Due to the novel coronavirus infection, he experienced syncope, decreased blood pressure and unclear consciousness after self-administration of 3 doses of nirmatrelvir 300-mg/ritonavir 100-mg (Paxlovid). Continuous intravenous infusion of dopamine 200-mg/d was given. Two hours later, his blood pressure was 103/46-mmHg, heart rate was 50 beats/min, and blood oxygen saturation was 0.92; electrocardiogram showed sinus bradycardia (45 beats/min), and complete right bundle branch block. Antihypertensive medications were discontinued, his blood pressure gradually increased to 116/82, and dopamine was discontinued. After 5 days of antihypertention drug withdrawal, the patient′s blood pressure was 169/93-mmHg and antihypertensive drug treatment was gradually resumed, 8 days later, the patient′s blood pressure was 130/78-mmHg. The possibility of neurogenic, cardiogenic, and reflexive syncope were excluded through physical examination, long-term electroencephalography, virus antibody testing, head magnetic resonance imaging, electrocardiogram, myocardial enzyme testing, and other related tests. The occurrence and recovery time of hypotension syncope in the patient were consistent with the inhibition and recovery time of cytochrome P450 (CYP) 3A4 by ritonavir. Benidipine was mainly metabolized through CYP3A4 in the liver. Therefore, it was considered that the hypotension syncope in the patient was related to the enhanced antihypertensive effect of benidipine by ritonavir.