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Adverse Drug Reactions Journal

1999  (1,  1)  to  Present  ISSN: 1008-5734

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Acute pancreatitis induced by oral azathioprine tablets in a myasthenia gravis patient

Dayong ZENG ; Jiashan DONG ; Pinfang HUANG ; Changlian WANG ; Rongfang LIN

Adverse Drug Reactions Journal.2020;22(1):48-49. doi:10.3760/cma.j.issn.1008-5734.2020.01.012

A 65-year-old male patient was treated with pyridostigmine bromide tablets (30 mg thrice daily), azathioprine tablets (75 mg twice daily), and prednisone acetate tablets (15 mg once daily) for myasthenia gravis. Two months later, the patient developed abdominal pain, nausea, and vomiting. The laboratory tests showed the blood lipase (LPS) 909 U/L and the urine amylase (AMS) 3 838 U/L. The results of abdominal ultrasonography and imaging examination were consistent with the manifestations of pancreatitis. Above-mentioned drugs were not stopped and the patient was treated according to the conventional treatment regimen of acute pancreatitis. However, the symptoms did not improved significantly. On the 11th day after the onset of the disease, he received subcutaneous infusion of octreotide injection, intravenous infusion of pantoprazole sodium for injection, oral metronidazole, and supportive treatments such as fluid supplement and correction of water electrolyte disorders. The laboratoty tests the next day showed that the patient′s blood LPS was 3 332 U/L and AMS was 139 U/L. The acute pancreatitis was considered to be related to azathioprine tablets. Then the drug was stopped and other treatments were continued. The patient′s symptoms improved quickly. Four days later, LPS was 546 U/L and AMS was 49 U/L.

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Clinical and pathological features of drug-induced liver injury due to non-steroidal anti-inflammatory drugs

Lijie GUO ; Chao WANG ; Xiaojing WANG ; Haicong ZHANG ; Lihong YE

Adverse Drug Reactions Journal.2020;22(2):62-68. doi:10.3760/cma.j.issn.1008-5734.2020.02.003

Objective:To explore the clinical and pathological features of drug-induced liver injury (DILI) due to non-steroidal anti-inflammatory drugs (NSAIDs).Methods:The medical records of patients with discharged diagnosis of drug-induced liver injury, which were searched from the Hospital Information System of Shijiazhuang Fifth Hospital from January 1, 2013 to December 31, 2016, were collected and analyzed retrospectively. The patients with DILI due to NSAIDs were enrolled into the NSAIDs group and the patients with DILI due to other drugs were enrolled into the control group. The general conditions, results of laboratory tests, and detection results of liver histopathology in patients in the 2 groups were recorded. The score of Roussel Uclaf Causality Assessment Method (RUCAM), clinical type and classification, pathological type and classification, and clinical outcome evaluation of the DILI patients in the 2 groups were performed according to the relevant standards by the members of research team.Results:A total of 385 patients were enrolled into the study, including 63 cases in the NSAIDs group and 322 cases in the control group. The differences of sexual distinction, age, and clinical manifestation were not statistically significant ( P>0.05 for all). The results of types and severity classification of DILI based on R value showed that the differences of the proportion of patients with different DILI types and classifications between the 2 groups were not statistically significant ( P>0.05 for all). Forty-one and 142 patients underwent liver biopsy in the NSNIDs group and the control group, respectively. The results of liver biopsy showed that the proportion of patients with type of vascular injury in the NSAIDs group was significantly higher than that in the control group [4.9% (2/41) vs. 0 (0/142), χ 2=7.003, P=0.049]; the incidences of inflammation in the portal area and proliferation of bile duct in the NSAIDs group were statistically lower than those in the control group [(63.4%(26/41) vs. 93.7%(133/142), χ 2=25.544, P<0.001; 43.9%(18/41) vs. 76.1%(108/142); χ 2=15.337, P<0.001]; the incidence of hepatocyte steatosis in the NSAIDs group was significantly higher than that in the control group [22.0% (9/41) vs.9.2% (13/142), χ 2=4.925, P=0.026].After drug withdrawal and symptomatic treatments, differences in effective rate and recovery rate between the NSAIDs group and the control group were not statistically significant[88.9% (56/63) vs. 92.5% (298/322); 41.3% (26/63) vs. 52.5% (169/322), P>0.05]. There were no death in both groups. Conclusions:The clinical manifestations and clinical outcomes of patients with DILI due to NSAIDs were similar to those due to other drugs. The pathological characteristics of liver were that the incidence of inflammation and proliferation of bile duct in the portal area was lower than that of other drugs, and the incidence of hepatocyte steatosis was higher than that of other drugs. Vascular injury was also observed.

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Analysis of occurrence and influencing factors of liver injury related to amphotericin B

Yihui ZUO ; Lee EDWARD ; Weiping HU ; Xiaofen YE ; Jing ZHANG

Adverse Drug Reactions Journal.2020;22(2):77-84. doi:10.3760/cma.j.issn.1008-5734.2020.02.005

Objective:To explore the occurrence of hepatic injury related to amphotericin B and analyze its influencing factors.Methods:The medical records of inpatients, who received amphoteric B during hospitalization and had complete records of liver function before and after medication, were searched from the Hospital Information System of Zhongshan Hospital, Fudan University from January 2013 to December 2017 and analyzed retrospectively. Liver injury was classified and diagnosed according to the Guidelines for the diagnosis and treatment of drug-induced liver injury and its incidence was calculated. According to the age (≤45 or >45 years old), with or without history of liver injury/liver disease within 3 months before admission, the dosage form of amphotericin B (non-liposome or liposome), the maximum daily dose (<30 or ≥30 mg), the maximum daily dose/body weight (<0.5 or ≥0.5 mg/kg), with or without step-up dosage, the course of treatment (≤21 or >21 d), the cumulative dose (<600 or ≥600 mg), cumulative dose/body mass (<10 or ≥10 mg/kg), with or without combination use of liver-protective drugs, and with or without combination use of other drugs with hepatotoxicity, the patients were divided into 2 groups, respectively. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), alkaline phosphatase (ALP), and gamma-glutamyltransferase (γ-GT) were compared respectively in patients in each 2 groups with above-mentioned 11 different clinical features. The influencing factors of hepatic injury related to amphotericin B were analyzed using multivariate logistic regression analysis and multiple linear regression analysis, whose effect values were expressed as odds ratio ( OR) with 95% confidence interval ( CI) and standardized regression coefficient with 95 %CI and value of R2. Results:A total of 42 patients were enrolled, including 31 males and 11 females with ages from 13 to 92 years old and body mass (65.0±12.3)kg. Of the 42 patients, 26 patients were ≥45 years old; 15 patients had history of hepatic injury/liver disease; 30 patients used amphotericin B, 10 used amphotericin B liposome, and 2 used both of them; 25 patients received the maximum daily dose of amphotericin B <30 mg and the maximum daily dose/body mass <0.5 mg/kg, 17 patients had the maximum daily dose ≥30 mg and the maximum daily dose/body mass ≥0.5 mg/kg; 28 patients used amphptericin B with step-up dosage, 14 patients′ initial doses were the maximum daily dose; 24 patients′ cumulative dose of amphotericin B and the cumulative dose/body mass were <600 mg and <10 mg/kg, respectively, while 18 patients′ cumulative dose of amphotericin B and the cumulative dose/body mass were ≥600 mg and 10 mg/kg, respectively; 29 patients received combination use of hepato-protective drugs; 33 patients received combination use of other hepatotoxic drugs. The levels of TBil and ALT in 42 patients after amphotericin B treatment were obviously higher than those before medication ( P=0.019, P=0.017). Seven patients were diagnosed as drug-induced liver injury, the incidence of drug-induced liver injury was 16.7%. The result of multivariate logistic regression analysis showed that history of hepatic injury/liver disease within 3 months before admission was the independent risk factor for elevated γ-GT level after medication ( OR=2.029, 95 %CI: 1.037-3.970, P=0.039). The results of multiple linear regression analysis showed that the maximum daily dose ≥30 mg and the cumulative dose ≥600 mg were the independent risk factors for elevated TBil level after medication (standardized regression coefficient: 0.59, 95 %CI: 0.28-0.90, P=0.001; standardized regression coefficient: 1.61, 95 %CI: 0.14-3.07, P=0.033; R 2=0.524); hepatic injury/liver disease within 3 months before admission was the independent risk factor for elevated ALP and γ-GT levels after medication (standardized regression coefficient: 0.85, 95 %CI: 0.25-1.45, P=0.006, R 2=0.205; standardized regression coefficient: 0.89, 95 %CI: 0.29-1.50, P=0.005, R 2=0.206). Conclusions:The incidence of liver injury related to amphotericin B in Zhongshan Hospital, Fudan University is 16.7%. The maximum daily dose of amphotericin B ≥30 mg and cumulative dose ≥600 mg are the independent risk factors for the elevated level of TBil, history of hepatic injury/liver disease within 3 months before admission is the independent risk factors for elevated levels of ALP and γ-GT.

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Death from acute liver failure due to concomitant use of propacetamol hydrochloride, cefuroxime sodium, and low molecular weight heparin calcium

Xianchao LI ; Jing LI ; Jixia REN ; Yan LU ; Maozhi HAN ; Shenghui LI ; Shasha LI

Adverse Drug Reactions Journal.2020;22(2):113-115. doi:10.3760/cma.j.issn.1008-5734.2020.02.013

A 62-year-old male patient received propacetamol hydrochloride for analgesia, cefuroxime sodium for anti-infection, adenosine cobalamin for nutrition of nerve, and low molecular weight heparin calcium for anticoagulation for burst fracture of the third lumbar vertebra and multiple fractures of transverse process of lumbar spine caused by traffic accident. The patient′s liver function was normal before medication. He underwent the operation under general anesthesia 2 days later. Low molecular weight heparin calcium was stopped before the operation. On day 3 after the operation (on day 5 of medication), the patient developed abdominal distension and pain. The results of laboratory tests showed alanine aminotransferase (ALT) 9 315 U/L, aspartate aminotransferase (AST) 10 760 U/L, gamma glutamyltransferase (γ-GT) 47 U/L, alkaline phosphatase (ALP) 101 U/L, total bilirubin (TBil) 71.3 μmol/L, direct bilirubin (DBil) 48.5 μmol/L, and indirect bilirubin (IBil) 22.8 μmol/L. Drug-induced liver injury was considered. Propacetamol hydrochloride was discontinued and liver-protective drugs were given. The next day, the patient developed yellow staining of his sclera and whole body skin, then followed by confusion, decreased blood oxygen saturation, low blood pressure, and hypoglycemia. The results of reexamination showed ALT 5 975 U/L, AST 3 659 U/L, γ-GT 100 U/L, ALP 141 U/L, TBil 175.2 μmol/L, DBil 101.4 μmol/L, IBil 73.8 μmol/L, and prothrombin time 21.2 s. The patient was diagnosed as acute liver failure. Cefuroxime sodium and adenosine cobalamin were discontinued and symptomatic and supportive treatments such as increasing blood pressure, fluid supplement, and correction of acidosis were given. However, the patient′s condition was not improved. He was transferred to other hospital on the same day. On the 4th day, he died of multiple organ failure.

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Anaphylactic shock caused by an intravenous infusion of moxifloxacin

Hong MU ; Lili WANG ; Jun LI

Adverse Drug Reactions Journal.2020;22(2):119-120. doi:10.3760/cma.j.issn.1008-5734.2020.02.016

A 75-year-old female patient received an intravenous infusion of moxifloxacin hydrochloride injection 0.4 g for prevention of infections after lumbar operation. About 10 minutes later, the patient developed sudden general discomfort, wet and cold skin, drenching sweats. Meanwhile her heart rate was 130 beats/min, breath rate was 26 times/min, and blood pressure was 57/37 mmHg. Anaphylactic shock caused by moxifloxacin was considered. Moxifloxacin was stopped immediately, ECG monitoring and oxygen inhalation through nasal catheter were given. Then, intravenous injection of adrenaline hydrochloride injection 0.5 mg, furosemide injection 10 mg, nitroglycerin injection 2.5 mg, and sublingual metoprolol tartrate tablet 12.5 mg were given successively. After 80 minutes, the patient′s symptoms relieved, with heart rate 88 beats/min, breath rate 18 times/min, and blood pressure 95/54 mmHg.

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Scleroderma-like changes of both lower extremities caused by gemcitabine chemotherapy

Yafang QIAN ; Chunyan LING

Adverse Drug Reactions Journal.2020;22(2):105-106. doi:10.3760/cma.j.issn.1008-5734.2020.02.009

A 63-year-old female patient received gemcitabine (1.2 g by an IV infusion on the first day) and carboplatin combination chemotherapy (500 mg by an IV infusion on the second day) because of postoperative recurrence of ovarian cancer. After finishing the first chemotherapy, the patient had slight edema and stabbing pain of both legs, and the skin from ankle to the middle of both legs gradually turned reddish. Then the stabbing pain and edema were gradually relieved and the epidermis was gradually thickened. After finishing the second chemotherapy, the skin stabbing pain and edema of both lower extremities were aggravated. During the interval of chemotherapy, the stabbing pain and edema were gradually reduced, but the skin of her legs gradually turned dark brown, the epidermis became thick and hard, showing typical scleroderma-like changes. After finishing the third chemotherapy, the stabbing pain and edema of the lower extremities were aggravated again. Then the patient was lost to follow-up. No skin injury occurred during 6 times of paclitaxel liposome and carboplatin combination chemotherapy. So the scleroderma-like changes in the patient was considered to be related to gemcitabine.

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Analysis on clinical characteristics and risk factors of acute hepatic injury due to amiodarone hydrochloride injection based on one-year centralized monitoring

Fangfang WANG ; Weihong CHEN ; Zhiqiang HE ; Zheng XU

Adverse Drug Reactions Journal.2020;22(2):69-76. doi:10.3760/cma.j.issn.1008-5734.2020.02.004

Objective:To explore the clinical characteristics and risk factors of acute hepatic injury (AHI) due to amiodarone hydrochloride injection.Methods:The study was designed as centralized monitoring. The monitored subjects were patients who were hospitalized in Shanxi Bethune Hospital and received amiodarone hydrochloride injection from March 1, 2018 to February 28, 2019, in which the patients with virus hepatitis, autoimmune liver disease, primary carcinoma of liver or hepatic metastasis of malignant tumor, and abnormal liver function before medication were excluded when analyzing the clinical characteristics and risk factors of AHI due to amiodarone hydrochloride injection. The special clinical records of the patients, who developed abnormal liver function after medication and were adjudged as AHI by attending physician and clinical pharmacist, were established by specially-assigned person. The laboratory tests records of the patients treated with the drug were rechecked through the Hospital Information System every month. After finishing the monitoring, the electronic medical records of monitored subjects were collected by searching the Hospital Information System; the patients′ basic information, basic diseases, the total dose of amiodarone hydrochloride injection, combination drugs, the detection results of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) before and after application of amiodarone hydrochloride injection, the time from medication to AHI occurrence, and the clinical manifestations, treatment and outcome of AHI were recorded. The patients were divided into the AHI group and the non-AHI group and the clinical features between the 2 groups were compared. The indices of P<0.2 between groups were analyzed using the multivariable logistic regression model, and odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. Results:A total of 271 patients were enrolled into the study. Of them, 34 patients developed AHI, the incidence of AHI was 12.5%. The differences of sex distribution, age, height, body weight, total dose by intravenous medication, situations of other combination drugs (including antiplatelet drugs, statins, Beta-adrenergic blockers, anticoagulants, hormones, and antineoplastic drugs and etc.) between the AHI group and the non-AHI group (237 patients) were not statistically significant ( P>0.05 for all). The proportion of patients with coronary atherosclerotic heart disease in the AHI group was higher than that in the no-AHI group [58.8% (20/34) vs. 30.8% (73/237), χ 2=10.358, P=0.001]. The differences of ALT, AST and TBil levels between the 2 groups before application of amiodarone hydrochloride injection were not statistically significant ( P>0.05 for all). The levels of ALT, AST, and TBil in the AHI group were significantly higher than those in the non-AHI group after application of amiodarone hydrochloride injection [341 (176, 1175) U/L vs. 25 (16, 31) U/L, P=0.014; 439 (167, 1 586) U/L vs. 36 (24, 56) U/L, P=0.029; 36.0 (15.3, 42.1) μmol/L vs. 18.6 (14.8, 22.1) μmol/L, P<0.001], and also significantly higher than those in the non-AHI group ( P=0.006, P=0.026, P<0.001). Of 34 AHI patients, 19, 14 and 1 patients developed abnormal liver function on day 2, 3 and 5 of medication, respectively, all of them had no obvious clinical signs and symptoms. After being diagnosed as having AHI, 29 patients discontinued the amiodarone hydrochloride injection treatment, 3 changed to lidocaine, and 2 discontinued it after 1 and 3 days of continued medication, respectively. All 34 patients received symptomatic treatments such as liver-protective drugs, in which 32 patients (94.1%) were improved, including 25 patients (78.1%) with liver function within the reference range, 7 patients with ALT and AST levels within 2 times of upper limit of reference range values and their TBil level within the reference range. The other 2 patients (5.9%) developed multi-organ dysfunction syndrome, in which one patient returned with normal liver function after treatment and one died. The results of multivariate regression analysis showed that coronary atherosclerotic heart disease, combined basic diseases ≥3 kinds, and combination drugs ≥3 kinds were the independent risk factors for AHI due to amiodarone hydrochloride injection ( OR=3.209, 95 %CI: 1.537-6.704, P=0.002; OR=2.437, 95 %CI: 1.083-5.486, P=0.031; OR=3.172, 95 %CI: 1.507-6.677, P=0.002). Conclusions:AHI due to amiodarone hydrochloride injection occurred mostly within 3 days of medication, which are acute onset and no obvious clinical signs and symptoms. The AHI′s diagnosis is mainly based on liver function examination. Patients with coronary atherosclerotic heart disease, combined basic diseases ≥3 kinds, and combination drugs ≥3 kinds are independent risk factors for AHI due to amiodarone hydrochloride injection.

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Efficacy and safety of tenofovir disoproxil fumarate treatment during the second or third trimester of pregnancy for preventing mother-to-infant transmission of hepatitis B virus: a meta-analysis

Xiaoyan WU ; Xuesong GAO ; Ruyu LIU ; Jiang GUO ; Haodong CAI

Adverse Drug Reactions Journal.2020;22(2):85-94. doi:10.3760/cma.j.issn.1008-5734.2020.02.006

Objective:To systematically evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) treatment during the second or third trimester of pregnancy for preventing mother-to-infant transmission of hepatitis B virus (HBV).Methods:Randomized controlled trials (RCTs) and cohort studies on efficacy and safety of TDF in the second and third trimester of pregnancy for the prevention of mother-to- infant transmission of HBV were collected by searching related databases at home and abroad (up to July 20, 2019). Quality of RCTs and cohort studies were evaluated using bias risk assessment tool of Cochrane collaboration networks and Newcastle-Ottawa Scale, respectively. Meta-analysis was performed using RevMan 5.3 software. The continuous data were expressed using standardized mean difference ( SMD) and its 95% confidence interval ( CI). The effect values of meta-analysis of dichotomous variables were expressed using odds ratio ( OR) and its 95 %CI for effectiveness outcome or risk ratio ( RR) and 95 %CI for safety outcome. Results:A total of 12 studies (2 RCTs and 10 cohort studies) were entered, including 1 326 HBV-infected mothers and their 1 281 infants, of which 729 mothers took TDF (the TDF group) and 597 mothers were without intervention or took placebo (the control group) in the second or third trimester of pregnancy. The results of quality evaluation showed that one of the 2 RCTs was at low risk of bias and the other one was at high risk of bias; 9 of the 10 cohort studies were of high quality and one was of medium quality. The meta analysis for effectiveness outcomes showed that the baseline HBV DNA level in patients in the TDF group was significantly higher than that in the control group ( SMD=0.15, 95 %CI: 0.04-0.26, P=0.008), the prenatal HBV DNA level in patients in the TDF group was significantly lower than that in the control group ( SMD= -5.41, 95 %CI: -7.26--3.56, P<0.001), the proportion of mothers with HBV DNA undetected before delivery in the TDF group was significantly higher than that in the control group [20.3% (41/202) vs. 2.0% (4/203), OR=27.55, 95 %CI: 7.32-103.85, P<0.001], and the HBV infection rate of infants born to mothers in the TDF group was significantly lower than that in the control group [0.8% (5/618) vs. 9.1% (47/516), RR=0.13, 95 %CI: 0.07-0.27, P<0.001]. The meta analysis for safety outcomes showed that the differences in the incidence of birth defects, mortality, birth weight, height and head circumference between the TDF group and the control group were not statistically significant ( P>0.05 for all), the difference in the incidence of postpartum alanine aminotransferase level rise between the TDF group and the control group was not statistically significant ( P>0.05); the results of one study showed that the proportion of mothers with grade 1-2 asymptomatic creatine kinase increase in the TDF group was higher than that in the control group [7.2% (7/97) vs. 0 (0/100), P=0.006] and the differences in the incidence of other adverse pregnancy events and complications in the 2 groups were not statistically significant ( P>0.05 for all). Conclusion:The treatment of TDF in the second and third trimester of pregnancy can effectively prevent mother-to-infant transmission of HBV and has no significant impact on growth and development of the fetus.

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Red man syndrome induced by vancomycin in a premature infant

Na WANG ; Enxi XU ; Qiqi PAN ; Can LUO

Adverse Drug Reactions Journal.2020;22(1):46-47. doi:10.3760/cma.j.issn.1008-5734.2020.01.011

A 4-month-old premature infant with broncho-pulmonary dysplasia was hospitalized and received imipenem and cilastatin sodium combined with erythromycin for severe pneumonia. During hospitalization, erythromycin was stopped because of exacerbation of infection and replaced by vancomycin hydrochloride 60 mg dissolved in 5% glucose injection 15 ml by an IV infusion at a speed of 60 mg/h. About 10 minutes of vancomycin treatment, the infant developed cry and noisy and facial flushing. Then the infusion speed was slowed down, but the infant was still crying and his skin erythema increased, which gradually fused into pieces on his neck, chest and limbs. And his heart rate increased to 160 beats/min. Red man syndrome induced by vancomycin was considered. Vancomycin was stopped immediately and no antiallergic agents were given. About one hour later, the skin rash disappeared gradually and the heart rate decreased to 140 beats/min. The next day, the skin color returned to normal. Then teicoplanin combined with imipenem and cilastatin sodium were given according to the results of drug sensitivity test in sputum culture. The rash did not recur. Two weeks later, his pneumonia improved and he was discharged.

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Effect of dose adjustment based on doxofylline blood concentration monitoring on safety of combination of doxofylline injection and terbutaline solution for nebulizationor

Huibin SUN ; Zhong ZHANG ; Zheng LIU ; Huizhi ZHANG

Adverse Drug Reactions Journal.2020;22(1):32-37. doi:10.3760/cma.j.issn.1008-5734.2020.01.007

Objective:To explore the effect of dose adjustment based on doxofylline blood concentration monitoring on safety of combination of doxofylline and terbutaline for respiratory diseases.Methods:The subjects were selected from patients who received doxofylline injection, terbutaline sulphate solution for nebulizationor, and the combination of the two drugs and hospitalized in Department of Respiratory Medicine of Zhengzhou Second People′s Hospital from January 1, 2014 to December 31, 2018. Patients who met the inclusion criteria were divided into 3 groups: doxofylline group, terbutaline group, and combination of doxofylline and terbutaline group (combination group). All patients in the 3 groups were given conventional treatments and symptomatic treatments. Doxofylline 300 mg once daily was given by an IV infusion and terbutaline 2 ml (5 mg) thrice daily was given by atomized inhalation for 7-14 days. Adverse reactions in the 3 groups were compared. The dosage of doxofylline in patients with adverse reactions of grade 1 was adjusted to 250 mg once daily, 200 mg once daily for patients with adverse reactions of grade 2, and doxofylline was stopped in patients with adverse reactions of more than grade 3. The blood concentration of doxofylline, the proportion of the patients whose adverse reactions were alleviated or disappeared, the length of hospital stay, and the efficiency of treatment before and after dose adjustment of doxofylline in patients in the doxofylline group and the combination group were compared.Results:A total of 6 582 patients were entered in the study. Of them, 1 438 patients were in the doxofylline group, including 793 males and 645 females with age of (61±11) years; 2 217 patients were in the terbutaline group, including 1 281 males and 936 females with age of (60±15) years; 2 927 patients were in the combination group, including 1 644 males and 1 283 females with age of (63±12) years. The differences in gender, age distribution, basic disease, combined disease, and combination medication among the 3 groups were not statistically significant ( P>0.05). The overall incidences of adverse reactions in the 3 groups were 13.1% (189/1 438), 8.9% (197/2 217), and 21.2% (620/2 927), respectively, which was higher in the combination group than that in the doxofylline group ( χ 2=41.271, P<0.001) and the terbutaline group ( χ 2=142.766, P<0.001) and higher in the doxofylline group than that in the terbutaline group ( χ 2=16.738, P<0.001). The incidences of tremor and headache in the combination group were higher than those in the other 2 groups( P<0.001), the incidence of hyperglycemia was higher than that in the doxofylline group( P=0.003), the incidence of insomnia was higher than that in the terbutaline group( P<0.001), the incidence of tachycardia was higher than that in the terbutaline group( P<0.001), the incidence of nausea was lower than that in the doxofylline group( P<0.001) and higher than that in the terbutaline group( P<0.001), the incidence of mood disorders was higher than that in terbutaline group ( P=0.017). No adverse reactions of more than grade 3 occurred in the 3 groups, the difference in proportions of patients with adverse reactions of grade 1 and grade 2 was not statistically significant( χ 2=1.097, P=0.578). The difference in blood concentration of doxofylline in patients with adverse reactions between the combination group and the doxofylline group was not statistically significant before dose adjustment ( P>0.05), but all decreased after dose adjustment (all P<0.001) and the blood concentration of doxofylline in the combination group was lower than that in the doxofyllin group [(8.38±2.19) μg/ml) vs. (10.64±2.55) μg/ml, P<0.001]; the proportion of patients whose adverse reactions were alleviated or disappeared in the combination group was higher than that in the doxofylline group [40.81% (253/620) vs. 30.16% (57/189), P=0.008], the hospitalization time was shorter than that in the doxofylline group [(10±2) d vs. (15±3) d, P<0.001], the treatment efficiency was higher than that in the doxofylline group [531 (85.65%) vs. 136 (71.96%), P<0.001]. Conclusion:When doxofylline injection is combined with terbutaline solution for nebulizationor, the blood concentration of doxofylline can be controlled at (8.38±2.19) μg/ml by monitoring the blood concentration of doxofylline, which can not only improve the treatment efficacy, but also improve the medication safety.

Country

China

Publisher

Chinese Medical Journals Publishing House Co., Ltd.

ElectronicLinks

http://www.cadrj.com/EN/home

Editor-in-chief

Li Lin

E-mail

cadrj@sina.com

Abbreviation

ADRJ

Vernacular Journal Title

药物不良反应杂志

ISSN

1008-5734

EISSN

Year Approved

2025

Current Indexing Status

Currently Indexed

Start Year

1999

Description

Adverse Drug Reactions Journal (药物不良反应杂志, ADRJ) is an academic journal issued domestically and internationally, which is sponsored by Chinese Medical Association and supervised by China Association for Science and Technology. It was founded in 1999 and published monthly, ISSN was 1008-5734. Its founder was professor Cheng Jinghua (程经华), who was the major pioneer and initiator of the monitoring work on adverse drug reactions in China. The idea of the journal is to run its own characteristics, make its best products, strive for its fame, and go to the world. Professor Li Lin, the current editor-in-chief, is the chief expert of the Pharmaceutical Department of Xuanwu Hospital, Capital Medical University, the vice president of the Chinese Pharmacological Association, the president of the Beijing Pharmacological Association, etc. He has served as the vice president of Xuanwu Hospital of Capital Medical University, the director of the Pharmaceutical Research Office, the deputy director of the National Clinical Research Institute of Drugs, the executive deputy director of the Key Laboratory of Neurodegenerative Diseases of the Ministry of Education, and the director of the Beijing Neuropharmaceutical Engineering and Technology Research Center. The journal has a sound editorial committee with consultants such as academician of Chinese Academy of Sciences, professor Chen Keji (陈可翼), and academician of Chinese Academy of Engineering, professor Gao Runlin (高润霖), Ning Guang (宁光), and Zhong Nanshan (钟南山). Editorial members come from 28 provinces, autonomous regions, municipalities directly under the Central Government, the United States and Singapore, covering clinical medicine (cardiovascular, respiratory, gastroenterology, nephrology, neurology, psychiatry. endocrinology, rheumatology, hematology, infectious diseases, oncology, allergy, dermatology, ophthalmology, etc.), pharmacology (clinical pharmacy, clinical pharmacology, pharmaceutics, pharmacoeconomics, pharmacy administration, etc.), nursing, clinical toxicology, pharmaceutical epidemiology, evidence-based medicine, statistics, and other disciplines. ADRJ focuses on the release of academic achievements in adverse drug events (adverse drug reactions, medication errors and drug quality defects), drug-induced diseases, and medication safety. The aims of the journal are to promote communication of drug safety information through reporting adverse drug reactions and their occurrence rules, improve clinical safe drug use level, protect public drug use safety and serve public health. The main columns include editorial, forum, original article, review, practice and research on clinical medication safety, pharmacist case record, case report, poisoning treatment, adverse reaction of traditional Chinese medicine, and historical story of drug accident, etc. Referring to the Reactions Weekly, ADRJ takes timely reporting new and serious adverse drug events as its feature. Among the reported adverse drug reactions, there is the first case reported globally or nationally. For example, the rhabdomyolysis induced by telbivudine published in 2009, which is the first case in the world, and the infliximab-induced aplastic anemia published in 2012, which is the first case in China and the second case in the world. ADRJ is a peer-reviewed journal and insists on the quality first of the manuscript. The journal follows relevant national standards and Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals. At present, ADRJ is the statistical source journal of “Chinese Science and Technology Paper Citation Database (CSTPCD)”, the source journal of “Chinese Science Citation Database (CSCD)” and is indexed by Ulrich's Periodicals Directory and International Pharmaceutical Abstract. In January 2020, ADRJ was officially included in Scopus, which is owned by Elsevier B.V. and is the largest peer-reviewed literature abstract and citation database in the world. The Scopus Content Selection & Advisory Board (CSAB) evaluate the journal as follows: Timely and accurate drug reaction reporting has global significance. The Chinese experience in this field is thus hugely important, particularly given the scale of the Chinese population and the reach of the Chinese pharmaceutical industry. It raises the journal directly from national to global importance. The journal has been recognized by the important international retrieval system, and the internationalization process of the journal has made great progress. Because the contents inosculate closely to the clinic with strong technicality and practicability, the issue of the journal not only covers in 34 provinces, autonomous regions and municipalities across the country, including Hong Kong, Macao and Taiwan, but also in the United States, the United Kingdom, Germany, France, Australia, New Zealand, Japan, South Korea, Singapore, Malaysia, and other countries. The fruitful work since its inception has established its academic status in the field of adverse drug reaction monitoring and medication safety in China. In September 2012, the National Health and Family Planning Commission decided to set up a clinical medication safety group under the INRUD China Central Group and establish a clinical medication safety monitoring network. The relevant work was entrusted to adverse drug reactions Journal Agency. To better implement the aims of the journal, various forms of academic activities were also held, including the China Forum on Drug-induced Diseases and Medication Safety, the hot topic discussion on medication safety, the difficult case discussion, the special academic seminar, the adverse drug reaction monitoring training course, etc. The China Forum on Drug-induced Diseases and Medication Safety has become an important distinguished academic meeting about clinical drug safety application, which has been held annually since 2009. The Adverse Drug Reaction Journal will, as always, adhere to the aims of running the magazine, never forget the original intention and forge ahead! Address: Room 1089, Teaching Building, Xuanwu Hospital, Capital Medical University, Donghuajinzuo, No.118, Guang’anmennei Street, Xicheng District, Beijing 100053, China Post code: 100053 Website: www.cadrj.com

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