Pattern of cutaneous adverse drug reactions in an adverse drug monitoring center at a tertiary care hospital in Kerala

Background: Pre-marketing clinical trials can filter only about 50% of the drug reaction. Hence, to prevent the morbidity and mortality due to severe cutaneous reactions early detection, evaluation and monitoring of adverse drug reaction (ADR) especially cutaneous ADR (CADR) are mandatory. Hence, it is imperative that we update our knowledge of the precise nature of ADR which will prevent the reactions as well as to find the offending drug. Aim and Objectives: The aim of the study was to evaluate the pattern of CADR, the suspected drugs and to perform the causality assessment using WHO casualty assessment scale. Materials and Methods: A retrospective descriptive study was done using the data reported to ADR monitoring center in the Department of Pharmacology by the health-care professionals. Suspected CADR was diagnosed by the consultants concerned. The CADRs collected were categorized according to their morphology into maculopapupar rash (MPR), fixed drug eruptions (FDE), urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The causality assessment was done using WHO Causality assessment scale. Results: The mean age was 47.20 + 22.31. The most common CADR reported was Urticaria 65.5% followed MPR 23%, FDE 8.8%, and Steven Johnsons Syndrome 2.2%. Anti-microbial drugs were the most frequent cause of the adverse reactions with Amoxicillin clavulinic acid combination being the most frequent suspected drug producing CADR (13.3%). The WHO causality assessment for majority of CADR was Possible (73.5%). Conclusion: Clinical Patterns of CADRs in this set up have some minor variations when compared to studies done across India. Amoxicillin clavulinic acid is the most common suspected drug in this study which was not frequently reported in other ADR monitoring centers.

Class-imbalance Prediction and High-dimensional Risk Factor Identification of Adverse Reactions of Traditional Chinese Medicine with Centralized Monitoring in Real-world Hospitals / 中国实验方剂学杂志

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Knowledge, attitude, and practice on adverse drug reaction monitoring among health-care professionals in a tertiary care hospital

Background: Pharmacovigilance has constantly gained importance in the past 15 years, relating to absolute amount of adverse drug reactions (ADRs) and to the fact that several hospital admissions are due to ADRs. Knowledge of ADRs and practice of pharmacovigilance by healthcare professionals will definitely help to evaluate the quality of pharmacotherapy in hospitals and effectively decrease the occurrence of ADRs. Aims and Objectives: The objectives are as follows: (1) To assess the knowledge, attitude, and practice of health care professionals (HCPs) toward ADR monitoring and (2) to assess the causation of underreporting of ADRs. Materials and Methods: This study was a cross-sectional questionnaire-based study. The questionnaire was distributed to 328 HCPs which included al doctors, nurses and pharmacists serving in ESIC Medical College and Hospital, Kalaburagi. HCPs who did not give consent to fill the questionnaire were excluded from the study. Results: The response rate was 82.92%. In our study, only 25.75% were aware that ADR reporting is to be done by doctors, nurses and pharmacists, and 40.44% felt that ADR reporting should primarily done by doctors alone. Overall participants who knowledge about ADRs and pharmacovigilance were 48.8%. Although 75.7% participants agreed that ADR reporting is important, over 76.5% HCPs felt that reporting ADR would be an obligation. In this study 12.5% HCPs have ever reported ADR despite having experienced one during their clinical practice. Majority of the HCPs had a belief that a single ADR reporting would not change the ADR database; hence, this could be one of the reasons for low rate of reporting ADRs. Conclusion: In our study, though the level of knowledge and attitude toward ADR reporting was adequate among the HCPs, there was poor practice of ADR reporting. Necessary measures to be taken to create awareness among HCPs about Pharmacovigilance Programme in India. They should be trained to spontaneously report ADRs.

Participation of clinical pharmacists in pharmaceutical care for a patient with Mycobacterium abscess infection after the resection of intervertebral schwannoma / 中国药房

OBJECTIVE To provide ideas for pharmaceutical care of Mycobacterium abscess infection. METHODS The diagnosis and treatment plan ，about a patient with M. abscess infection after resection of intervertebral neurilemmoma participated by clinical pharmacists ，was analyzed . According to the results of bacterial culture and drug sensitivity test of wound secretion ，the clinical pharmacist timely dealed with the adverse drug reactions during the treatment . For the tinnitus caused by the patient taking amikacin（0.4 g，intravenous drip ，q12 h），it was suggested to stop amikacin and replace it with linezolid ；however，the patient suffered from knee pain after taking linezolid . The clinical pharmacist once again suggested stopping linezolid ，continuing to use amikacin，and adjusting the dose to 0.8 g，intravenous drip ，q24 h；at the same time ，the patients were given medication guidance and ordered to have regular follow -up after discharge . RESULTS The physicians adopted the suggestions of clinical pharmacists ， and the patient did not suffer from tinnitus ，knee pain and other discomfort ，and the liver and kidney functions were normal . CONCLUSIONS Clinical pharmacists timely assist clinicians to adjust the medication plan ，which improves the effectiveness and safety of patients ’medication.

Blood glucose related adverse drug reaction of antitumor monoclonal antibodies: a retrospective analysis using Vigibase

Abstract On the increasing prevalence of using mAbs (monoclonal antibodies) in cancer therapy and the severe risk of hyperglycemia, we aimed to analyze the main clinical ADRs of mAbs, with a focus on adverse hyperglycemic events associated with currently clinically used mAbs. mAbs as well as target information were selected from Martinadale book and published articles. Drug approving information was collected from each government website, and ADR statistic data were collected from VigibaseR, comparing with Adverse Event Reporting System of US FDA. Top 10 mAbs were classified within listing in total ADR records, ADRs per year, hyperglycemic ADR records. Vigibase data were updated onto 15 Feb 2019. 20 mAbs were analyzed with 263217 ADR reports, wherein 16751 records on Metabolism and nutrition disorders and 1444 records on Glucose metabolism disorders. The geographic, age, gender distributions and annual ADR report numbers were listed respectively. Of the top 10, Rituximab, Bevacizumab and Nivolumab were on the top 3 in total ADR record and hyperglycemic record. Top 3 record results were similar in Vigibase and FDA database. It is of increasing importance for clinicians to be aware of early detection, patient management, or drug selection strategies when using mAbs, particularly within the high glycemic risk-reported mAbs, to improve the efficacy and tolerability of mAbs regiment and optimize patient outcomes.

Data mining and analysis of febuxostat-induced cardiac ADR signals / 中国药房

OBJE CTIVE To mine and analyze t he cardiac adverse drug reaction （ADR）signals induced by febuxostat in post-marketing experience ，and to provide reference for rational drug use in clinic. METHODS Reporting odds ratio （ROR） method was used to mine the ADR signals induced by febuxostat from the FDA Adverse Event Reporting System during the first quarter of 2009 to the fourth quarter of 2020；the information of cardiac disease signals was counted and analyzed. RESULTS A total of 209 ADR signals were detected in 8 282 adverse drug event （ADE）reports with febuxostat as the primary suspected drug ， involving 27 cardiac signals and 754 ADE reports. The most reported signals were symptoms （262 reports），including dizziness ， oedema peripheral，chest pain ，palpitations and gravitational oedema and so on ，followed by coronary atherosclerotic heart disease signal，heart failure signal ，arrhythmia signal ，sudden cardiac death signal （233，157，90，12 reports，respectively）. More than half of the signals were mentioned in the drug instructions ，while the unmentioned signals were mainly kinds of cardiac failure ， arrhythmia and extrasystoles ，etc. The patients with cardiac ADEs who received febuxostat were more male than female ，and the age was 60 and over ；the drug dosage was mostly 40 mg/d or 80 mg/d as recommended in the drug instructions ，and cardiac ADEs mostly occurred within 1 month of medication. CONCLUSIONS Routine attention should be paid to the cardiac safety of febuxostat during medication ，further evaluation and validation of febuxostat-induced cardiac ADR signals are still needed.

Bibliometric analysis of status quo and hot spots of domestic and foreign pharmacovigilance research / 中国药房

OBJECTIVE To investigate th e status quo and hot spots of domestic and foreign pharmacovigilance research ，so as to provide reference for scientific evaluation of drug safety. METHODS Relevant literature were searched from Web of Science and CNKI during the inception to Mar. 31st，2021. Excel 2019 software and CiteSpace 5.7R2 software were used to visualize and analyze the co-occurrence ，clustering and burst of annual document volume ，researchers，countries/regions，institutions and keywords. RESULTS & CONCLUSIONS A total of 5 422 foreign literature and 966 domestic literature were included ，with an increasing trend year by year. The cooperation between foreign researchers was relatively close ，while the cooperation between domestic researchers was less. A close network of cooperation was set up ，mainly in Europe and the United States. China although the late start ，but since 2018，there was a relatively rapid development trend and has continued so far. In domestic literature ，the organizations with a large number of published literature were mainly national medicine regulatory authorities ，research institute ， colleges and universities ，the cooperation of them was relatively weak. ADR ，drug safety and relevant risk factors are the research hotspots of pharmacovigilance abroad ；the frontier mainly focuses on pharmacovigilance research for vaccines ，drugs and therapeutic methods. The current research hotspot in China is ADR ，and special attention is paid to the safety of traditional Chinese medicine. The establishment of pharmacovigilance system of “Drug Marketing Authorization Holders ”is the research frontier. In the process of drug safety evaluation ，attention should be paid not only to the monitoring and reporting of ADR ，but also to the evaluation and application of multi-link and multi-dimensional research evidence of pharmacovigilance ，so as to effectively promote safe and rational drug use.

Literature analysis of leflunomide-induced interstitial pneumonia / 中国药房

OBJECTIVE To study the clinical characteristics of leflunomide-induced int erstitial pneumonia （Lef-IP），and to provide reference for its clinical diagnosis ，treatment and prevention. METHODS Lef-IP cases published in domestic and foreign journals from January 2004 to June 2021 were collected. Relevant information of patients were extracted and analyzed retrospectively， including basic characteristics ，clinical manifestations ，imaging manifestations ，laboratory examinations ， histopathological examinations ，treatment and outcome. RESULTS A total of 54 Lef-IP patients from case reports of 24 publications were included ，with a median age of 61 years（9-83 years）. Pulmonary symptoms appeared from 3.3 weeks to 132.9 weeks（median time of 14.5 weeks）. Patients with a loading dose of leflunomide have a shorter median time to pulmonary symptoms appearing （7.5 weeks）. The main clinical manifestations were dyspnea （85.2％），cough（57.4％），fever（53.7％）. CT imaging examination showed 19 cases with ground-glass shadow in both lungs ，and 29 cases showed interstitial infiltration in both lungs on chest radiograph；blood gas analysis showed hypoxemia and hypocapnia ；the levels of C-reactive protein and Krebs von Den lungen- 6 （KL-6）increased；histopathological examination mainly showed interstitial pneumonia （8 cases），including 3 cases of diffuse alveolar injury ，4 cases of lymphocytes in bronchoalveolar lavage fluid ，and 1 case of noncaseating granuloma. After discontinued leflunomide and symptomatic treatment （antibiotics，hormones，colecenamine，plasma exchange ），35 patients（64.8％）recovered or improved their lung symptoms. Twelve patients （22.2％）died，and patients with fever may had a higher mortality rate （34.5％， P＝0.02）. CONCLUSIONS The main clinical manifestations of Lef-IP are dyspnea ，cough and fever. Loading doses of leflunomide should be avoided at the beginning of treatment. When lef-IP occurs ，leflunomide is discontinued and corresponding treatment is given，and most of the patients ’pulmonary symptoms can return to normal or be improved.

Analysis of the Reports of Adverse Dug Reaction Induced by EGFR-TKI in Shandong Province / 中国药房

OBJECTIVE：To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR）induced by EGFR-TKI，and to provide reference for safe use of drugs in clinic. METHODS ：The relevant data of EGFR-TKI-induced ADR reports which were reported to Shandong ADR Monitoring Center from January 2018 to December 2020 were summarized ，and analyzed statistically in respects of age ，gender，drug variety ，ADR classification ，usage and dosage ，occurrence time ，involved organs/systems，clinical manifestations and prognosis of patients. RESULTS & CONCLUSIONS ：A total of 120 ADR reports induced by EGFR-TKI were included ，involving 120 patients. Among 120 patients，the female （60.83％）was more than the male （39.17％），and the age was mainly 50-79 years old （79.16％）. A total of 5 drugs including gefitinib ，ositinib，afatinib，ektinib and erlotinib were involved. ADR occurred in 72，11，15，6 and 16 patients using the above drugs respectively ；the main ADR was general ADR （70.83％），followed by severe ADR （22.50％），new general ADR （5.00％）and new severe ADR （1.67％）. All patients were given drugs orally ，off-label use was found in 2 patients who used ektinib ，and the rest met the medication requirements of the drug instructions. ADR occurred in 61 patients（50.83％）within 1 month after medication ，34 patients （28.33％）within 1-3 months after medication ，25 patients（20.83％）within 4-12 months after medication ，and no ADR occurred after 12 months. ADR of organs/systems involved were mainly the lesion of skin and its appendant injury，gastrointestinal system injury and hepatobiliary system injury. The main clinical manifestations were rash ，diarrhea and abnormal liver function ；in addition，some patients developed severe or new severe ADR such as interstitial pneumonia ，bone marrow suppression ，tongue swelling and cerebral infarction. Totally 102 patients recovered or improved after drug withdrawal or symptomatic treatment ，12 patients had unknown outcome ，and 6 patients did not improve. It is suggested that pharmaceutical care should be strengthened within 1 month after EGFR-TKI administration ，so as to guard against the occurrence of new and serve ADR and ensure the safety of clinical medication.

ADR Signal Mining and Analysis of Adverse Drug Reaction of Ceritinib / 中国药房

OBJECTIVE：To initially evaluate the safety of ceritinib after it is marketed ，and to provide reference for the rational use of drug. METHODS The report odd ratio method and proportional reporting ratio method were used to mine the signals of ceritinib-related adverse events from FDA adverse event reporting system （FAERS）during the second quarter of 2014 to the third quarter of 2019. The patients ’gender，age，body weight ，daily dose and course of treatment were collected. SPSS 26.0 software was used to test the number of ADR cases of this system group and other system groups by chi square test. RESULTS ：A total of 10 318 ADR reports with ceritinib as the first suspicious drug were collected ， and 236 ADR signals of seretinib were excavated. After excluding the ineffective treatment ，187 ADR signals were obtained ，involving 16 systems. Inaddition to those mentioned in the drug instructions ，the signals also included various nervous disease ，blood and lymph system disease ，infections and infectious disease ，etc.，such as hand-foot-genital syndrome ，mutation of anaplatic lymphoma kinase gene. Among them ，the ADR reports of gastrointestinal diseases were the most （576 cases）. Compared with ADR of other systems ，gender，age，body weight，daily dose and treatment course had significant effects on ADR of gastrointestinal diseases （P＜0.05）. Most of the patient with gastrointestinal ADR after using ceritinih were female （59.9％），45 years old and above （70.3％），body weight ≤65 kg （68.1％），daily dose 451-750 mg/d（50.2％），and medication duration less than 3 months（75.7％）. CONCLUSIONS ：The risk of gastrointestinal ADR in female patients over 45 years old and with body weight less than 65 kg after using seretinib is relatively high. This kind of ADRs are also related to daily dose ，and most of which occur within 3 months. Therefore ，great importance should be attached to drug monitoring during clinical use.

Preliminary Study on China ’s Insurance Model for ADR Injury Compensation under MAH System / 中国药房

OBJECTIVE：To construct China ’s Insurance Mode for ADR injury compensation model under marketing authorization holder （MAH）system，and to provide reference for reducing the medical disputes caused by ADR damage and protecting the rights and interests of patients. METHODS ：Using the methods of recommendation and “snowball”，the interviewers were invited to conduct semi-structured interviews to obtain qualitative data ，and the results were analyzed by thematic analysis. According to the results of subject analysis ，the ADR injury compensation model was designed from three aspects of insurance type setting，insurance level division and compulsory insurance protection objects ，and the Fuzzy comprehensive evaluation method based on AHP was used to evaluate the model ；questionnaire and multiple factor Logistic regression analysis was adopted to analyze the influential factors of whether drug related institutions were willing to establish ADR injury compensation system. RESULTS：A total of 40 experts were invited and 34 of them completed the interview ，with a response rate of 85.0％. At present ， the problems of ADR injury compensation in China mainly included the difficulties of third-party identification and adducing evidence of ADR injury ，the difficulty of timely and fair settlement of medical disputes caused by ADR injury ，the high cost and long time of handling ADR injury disputes ，and the uncertainty of compensation mode. More than half of the experts interviewed agreed with the compensation mode of insurance . The overall score of established model was 89.50. A total of 640 questionnaires were distributed and 559 valid questionnaires were recovered （204 drug manufacturers ，172 drug distributors and 183 medical institutions）. The effective rate of the questionnaire was 87.3％. Multiple Logistic regression analysis showed that the factors positively correlated with the approval of establishing ADR injury compensation system after the implementation of MAH system in China included the familiarity of ADR staff in drug manufacturing enterprises with ADR related policies （β＝1.697，P＜0.05），the types of drugs operated by pharmaceutical companies （β＝2.987， P＜0.05），the cognitionlevel of medical staff on ADR （β＝ 2.800，P＜0.05）. The working years of medical staff were negatively correlated with the approval of establishing ADR injury compensation system after the implementation of MAH system （ β ＝－ 2.544，P＜0.05）. CONCLUSIONS ：ADR injury compensation model designed in this study is feasible. It has reference value for reducing the economic burden of ADR patients ， treating patients ’health problems caused by ADR injury in time ，and promoting the development of China ’s drug insurance. Main influential factors for the establishment of ADR injury compensation model under MAH system contain the familiarity of ADR staff in drug manufacturing enterprises with ADR related policies ，the types of drugs operated by pharmaceutical companies ，the cognitionlevel of medical staff on ADR ，the types of drugs operated by pharmaceutical companies ，the cognitionlevel of medical staff on ADR.

Piperacillin and Its Compound Preparation-induced Anaphylactic Shock ：A Case Report and Literature Analysis / 中国药房

OBJECTIVE：To i nvestigate the clini cal ch aracteristics of anaphylactic shock induced by piperacillin and its compound preparation ，and to provide reference for prevention and treatment of the severe ADR. METHODS ：A case of anaphylactic shock induced by piperacillin and sulbactam were analyzed in our hospital ，meanwhile ADR literatures about piperacillin alone and its compound preparation-induced anaphylactic shock were collected from Medline ，CNKI，Wanfang database and VIP during the inception to Jul. 2020. Gender and age of patients ，allergic history ，primary disease and treatment ，skin test ， administration route and dosage of piperacillin and its compound preparation ，occurrence time and main manifestations of anaphylactic shock ，treatment measure and prognosis were analyzed ，then prevention and treatment suggestions were put forward. RESULTS：The patient in this case was transferred to the ICU after partial hepatectomy. The use of piperacillin and sulbactam to prevent postoperative infection caused anaphylactic shock. A total of 28 literatures about anaphylactic shock induced by piperacillin and its compound preparations were collected from the database （involving 28 patients）. Among totally 29 patients，there were 12 male and 17 female；the majority of patients were 50-59 years old （6 cases，20.69％）. Three patients had allergic history （food， latex gloves ，etc.），and most of the primary diseases were infectious diseases or the drug used in perioperative period. Skin tests were carried out in 22 patients（75.86％）before medication and the results were negative. The possible allergenic drugs of 27 cases which were administered by intravenous route included piperacillin ，piperacillin sulbactam and piperacillin tazobactam. The dosage was different according to the primary disease and severity. 14 patients（55.56％）developed anaphylactic shock within 5 minutes after drug exposure. The main symptoms were systemic allergic reaction ，mainly involving the circulatory system. Except for two death cases ，the other patients ’symptoms were relieved after treatment. CONCLUSIONS ：Allergic history and skin test results may have limitation in predicting anaphylactic shock induced by piperacillin and its compound preparation. Close monitoring needs to be taken in patients during these medications. Rescue therapy should be prepared in advance and countermeasures need to be carried out promptly in case of anaphylactic shock.

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Case Analysis and Literature Review of a Case of Acarbose-induced Skin ADR by Clinical Pharmacists / 中国药房

OBJECTIVE：To summarize and analyze t he clinical characteristics of acarbose-induced skin ADR ，and to provide reference for its therapy. METHODS ：Clinical pharmacists participated in the treatment of a patient with acarbose-induced skin ADR. The patient developed erythema multiforme several days after oral administration of Acarbose tablets （100 mg/d）. After consultation by dermatology and clinical pharmacy ，considering that the adverse reaction was related to acarbose ，clinical pharmacists suggested to stop the drug. Based on the above cases ，clinical pharmacists searched Wanfang database ，CNKI， PubMed，Embase and other databases to collect case reports of skin ADR caused by acarbose ，summarize its general situation （gender，age，usage and dosage ，etc.），latency，ADR（diagnosis and manifestation ），intervention and outcome ，etc. RESULTS ： The doctor adopted the pharmacist s’advice，stopped the use of acarbose ，and gave symptomatic treatment as Methylprednisolone sodium succinate for injection 40 mg（intravenous injection ，qd）+Medloratadine tablets 8.8 mg（oral administration ，qd）+Calamine lotion（for external use ）. The patient improved and was discharged after 10 days. A total of 12 literatures involving 12 patients were retrieved. Among the 13 patients included in the analysis （including the above clinical case and 12 literature cases ），there were 8 males and 5 females，and 8 patients of them aged 50 and over；the dosage of acarb ose in most patients was within the requirements of the drug instructions. The primary diseases of 12 patients were diabetes mellitus. The latency of skin ADR in 11 patients was within 6 days of administration. Among the 13 patients，the ADR were diagnosed as rash in 4 cases，pustulosis in 3 cases， erythema multiforme in 2 cases， urticaria in 2 cases， maculopapular rash in 1 case and lip swelling in 1 case. The ADR of 1 patient improved after drug withdrawal ，and 12 patients also improved after drug withdrawal and symptomatic treatment such as glucocorticoid or antihistamine. Acarbose was re-used in 2 patients after the improvement of first skin ADR ，and skin ADR occurred again ，and the ADR were improved after drug withdrawal and symptomatic treatment. CONCLUSIONS ：Skin ADR are acarbose-induced rare ADR ，mostly within 6 days of medication ，and are more likely to occur in middle-aged and older men. When the patients suffer from ADR ，the drug should be stopped in time and given glucocorticoids or antihistamines for symptomatic treatment. Clinical pharmacists should do a good job in drug publicity and education ，remind patients to closely monitor relevant indicators and ensure drug safety.

Clinical Characteristics of Voriconazole-induced Neurological ADR and the Occurrence of Hypokalemia and Hyponatremia / 中国药房

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

Analysis of a Rare Case of Cerebral Infarction Secondary to Anaphylactic Shock Caused by Nicotinic Acid Injection / 中国药房

OBJECTIVE：To provide reference for safe use of Nicotinic acid injection in the clinic. METHODS ：The clinical pharmacist introduced the occurrence and treatment of cerebral infarction secondary to anaphylactic shock caused by Nicotinic acid injection in a patient with hypertension in the cardiovascular medicine department of our hospital. By consulting the relevant drug instructions and searching the relevant literatures ，the inducement and severity of ADR were evaluated ，and the rational drug use suggestions of Nicotinic acid injection were put forward. RESULTS & CONCLUSIONS ：According to the Management Measures for ADR Reporting and Monitoring ，the correlation between anaphylactic shock and Nicotinic acid injection was analyzed and evaluated as “very likely ”. Secondary cerebral infarction was mainly associated with a variety of risk factors （hypertension， hyperlipidemia，etc.），among which there was a greater possibility of secondary cerebral infarction due to insufficient cerebral perfusion caused by anaphylactic shock and sharp drop of blood pressure. The above symptoms could be life-threatening if not rescued in time ，which was defined as “severe ADR ”. Clinical pharmacists suggest that when using Nicotinic acid injection ，the patient’s allergy history should be inquired in detail ，the use should be started from a small dose ，and the patient ’s reaction should be closely monitored in the early stage of medication. For patients with high-risk factors of cerebrovascular diseases （hypertension， hyperlipidemia，etc.），if anaphylactic shock occurs ，the effective circulating blood volume should be restored as soon as possible. After the blood pressure rises ，drugs such as improving microcirculation can be used to prevent secondary cerebral infarction. Clinical pharmacists should timely carry out medication education for such patients ，and warn patients to inform doctors of the related drugs with severe ADR in the later stage of treatment ，so as to prevent the recurrence of anaphylactic shock and severe complications. At the same time ，when antihypertensive drugs and statins are combined ，the blood pressure monitoring and the monitoring of ADR such as muscle toxicity should be strengthened，so as to ensure the medication safety of patients.

Analysis of Drug Use in a Patient with Rare Camrelizumab-induced Toxic Epidermal Necrolysis by Clinical Pharmacists / 中国药房

OBJECTIVE：To introduce the role of clinical pharmacists in the treatment of camrelizumab-induced toxic epidermal necrolysis （TEN），and to provide reference for the therapy of similar ADR. METHODS：The clinical pharmacist participated in therapy duration of a patient with TEN caused by camrelizumab. The patient was treated with Camrelizumab for injection combined with Apatinib mesylate tablet as anti-tumor therapy，and was admitted to hospital due to extensive skin lesions. After consulting relevant literatures and analyzing the patient’s admission diagnosis [severe epidermolysis bullosa，severe drug eruption（erythema multiforme），abnormal liver function，etc.] and examination results（hypokalemia，etc.），clinical pharmacists suggested to stop above anti-tumor drugs and given Methylprednisolone sodium succinate for injection（160 mg→80 mg→60 mg， qd，ivgtt） for anti-inflammatory treatment，Imiperan cilastatin for injection （1 g，q8 h，ivgtt） for an ti-infection treatment， Potassium chloride injection（1 g，qd，ivgtt）for electrolyte regulation，Compound amino acid injection（3AA）（10.65 g，qd，ivgtt） for nutritional support treatment，Pantoprazole sodium for injection（40 mg，qd，ivgtt）for acid inhibition and stomach protection， Reduced glutathione for injection（2.4 g，qd，ivgtt）for liver protection. Before medication，the patient was given cognitive and behavioral education and medication publicity. The changes of relevant indicators were closely monitored during medication，and the patient was given medication guidance when he was discharged. RESULTS：The doctors adopted the suggestions of clinical pharmacists，and 16 days after treatment，the skin lesions of the trunk and limbs were improved，and the double eyelids were still erosive and exuded a lot of secretions. The patient requested transfer for treatment. CONCLUSIONS：Clinical pharmacists assisted physicians to improve the treatment plan of patients with TEN caused by camrelizumab，and carried out cognitive and behavioral education and medication publicity for patients to ensure the effectiveness and safety of their medication.

One Case of Hand-foot Syndrome Recurrence Induced by Sequential Paclitaxel Liposome for Injection with Doxorubicin Hydrochloride Liposome Injection and Literature Review / 中国药房

OBJECTIVE：To investigate the role of clinical pharmacists in the diagnosis and treatment of liposome-induced hand-food syndrome （HFS），and to provide reference for rational use of liposome preparation in clinic. METHODS ：One case of elderly female patient with breast cancer ，admitted to our hospital suffered from HFS （grade 2）after treated with Doxorubicin hydrochloride liposome ；after successful therapy ，the patient had skin symptoms （grade 3）again due to Paclitaxel liposome ，and clinical pharmacist judged the recurrence of HFS. For symptomatic treatment ，stopping the treatment and external use of hormone was suggested ，and whole-process pharmaceutical care was provided. The pathogenesis ，differential diagnosis ，risk factors and therapeutic drugs of HFS were summarized based on literature review and 2 case reports in the database. RESULTS ：The physicians adopted the suggestion of clinical pharmacists ；the patient ’s symptoms improved significantly on the third day and disappeared after 1 week. Combined with literature analysis and 2 case reports ，doxorubicin liposome metabolized more slowly than non liposomes in palms and soles of feet ，resulting in accumulation of doxorubicin in sweat duct and stratum corneum ，aggravating skin damage and leading to HFS. Sequential paclitaxel in liposome form may also lead to the accumulation in eccrine duct ，further caused skin damage and induced HFS. CONCLUSIONS ：Clinical pharmacists actively participate in the diagnosis and treatment of ADR ， which is conducive to the rehabilitation of patients. At same time ，combination or sequential of Paclitaxel liposome with PLD should be avoided ，as it can lead to ADR as HFS.

An Observational Study of the Knowledge, Attitude and Practice of ADR Reporting among the Junior Doctors of Jawaharlal Nehru Institute of Medical Sciences (JNIMS), Imphal.

One of the health problems which is associated during the management of a patient with series of drugs is ADR/ADE. Therefore, the aim of the present study was to find out the activities for improving the reporting of ADRs/ADEs. The data on the KAP is collected on a pre-tested questionnaire.METHODSThis is a non-interventional cross-sectional study. The questionnaire was prepared after referring the questionnaires of previous studies. Out of 120 questionnaires distributed, only 100 questionnaires were received back. Descriptive statistics is used for analysing the data.RESULTSThe response on the questionnaire is 83.3%. Seventy-nine (79) participants knew the definition of ADR/ADE. Eighty-eight (88) participants want to report the ADRs of the marketed drugs irrespective of new or old. Seventy-five (75) participants know about PvPI. Ninety (90) participants do not consider all the OTC and Herbal drugs are safe. Seventy-two (72) participants do not know the establishment of a Pharmacovigilance centre at the Department of Pharmacology, JNIMS. Only 55.6% of the participants oblige to report the ADRs as a professional health care provider. 58% of the participants opine to conduct a regular CME program on ADR/Pharmacovigilance. 63.2% participants state that maximum ADRs are seen among dermatological, paediatric and elderly patients. 58.2% of the participants express their opinion about the occurrence of ADRs/ADEs with irrational prescription, polypharmacy, foods, drinks etc. 44% participants have the attitude of reporting ADRs/ADEs but only 10% participants perform the actual reporting with careful observations on patients’ behaviour. Most of the ADRs/ADEs are avoidable if there is good communication and reporting.CONCLUSIONSA regular awareness programme on ADR/ADE along with CME program and also online reporting facilities is necessary for promotion of reporting of the ADR/ADE. Therefore, the drug should be prescribed rationally, and polypharmacy should be avoided as much as possible.

Adverse drug reactions and treatment outcome analysis in multidrug resistant tuberculosis patients at a DOTS plus site

Background: Multidrug resistant tuberculosis (MDR TB) requires treatment with expensive, toxic, anti-tubercular drugs over a longer duration. Adverse drug reaction (ADR) to second line anti tubercular drugs affect compliance and hence treatment outcome. The primary objective of this study was to analyse ADRs and if these resulted in change or permanent suspension of drug. We also analysed treatment outcome, treatment adherence and co morbidities associated with MDR patients.Methods: A retrospective study was carried out at DOTS plus site in department of Pulmonary Medicine, Goa Medical College on registered MDR cases from November 2011 to October 2016. Socio demographic profile, diagnosis, treatment and ADRs were evaluated, ADRs were evaluated for frequency, causative drugs, management aspect and impact on treatment outcome.Results: Out of 201 MDR cases, 99 cases had 167 ADRs. Majority of patients having ADRs were in age group of 30-50 years with mean眘tandard deviation 36.82�.47, 59 (59.59%) males and 40 (40.40%) females, 92 (92.92%) retreatment cases and 7 (7.07%) newly diagnosed. Majority of ADRs were vomiting 31(18.56%), joint pain 31 (18.56%), gastritis 21 (12.57%), hearing impairment 16 (9.58%), numbness in leg 14 (8.38%), depression 12 (7.18%). Treatment outcome of cases with ADR was cured 45 (45.45%), treatment completed16 (16.16%), progressed to XDR 6 (6.06%), transferred out 5 (5.05%), defaulter 14 (14.14%), death 13 (13.13%).Conclusions: It is very important to recognise at the earliest and treat the ADRs with least modification of the treatment regimen to have a good treatment outcome.