Aspectos farmacológicos y adherencia al tratamiento antirretroviral en pacientes VIH

Introducción: La adherencia al tratamiento farmacológico favorece la supresión viral y reduce la resistencia a la terapia antirretroviral de gran actividad a largo plazo. Objetivo: Determinar la relación entre los aspectos farmacológicos y la adherencia al tratamiento antirretroviral de una IPS colombiana. Metodología: Estudio analítico transversal en pacientes con diagnóstico de VIH en tratamiento antirretroviral entre los años 2012 a 2020. Se utilizó un modelo de regresión logística binaria múltiple con fines explicativos. Resultados: Se analizaron 9835 pacientes donde la proporción de adherencia fue de 90 % y en el modelo ajustado se evaluó su relación con los antecedentes de no adherencia (ORa:0,52 IC95 °/o:0,40-0,66), grupo farmacológico (2 ITIAN + 1 IP u otro) (ORa:1,22 IC95 %:0,99-1,76), dos tomas al día (ORa:1,02 IC95 %:0,74-1,40), unidades al día (≥ 3) (ORa:0,69 IC95 %:0,47-1,02), reacciones adversas a medicamentos (ORa:0,56 IC95 °%:0,40-0,78), polimedicación (ORa:1,36 IC95 %:1,00-1,85), tiempo TAR (1 a 2 años) (ORa:1,63 IC95 %:1,27-2,09),tiempo TAR (6 a 12 meses) (ORa:1,66 IC95 %:1,27-2,18), tiempo TAR (<6 meses) (ORa:1,36 IC95 %:1,03-1,78), tasa de reclamación de los medicamentos (ORa:0,42 IC95 %:0,32-0,55) y antecedentes PRUM (ORa:0,11 IC95 %:0,09-0,14). Discusión: La proporción de adherencia obtenida es superior a lo descrito para otros países (entre 60-77 %); sin embargo se encuentra que los hallazgos correspondientes al efecto de las variables farmacológicas analizadas son acordes a lo descrito en estudios previos en el tema Conclusión: Los antecedentes de no adherencia, reacciones adversas, tasa de reclamación de los medicamentos y antecedentes de problemas relacionados con el uso de medicamentos son aspectos que reducen la probabilidad de adherencia; mientras que el mayor tiempo de uso del tratamiento aumenta la misma.

Introduction: Adherence to drug treatment promotes viral suppression and reduces long-term resistance to highly active antiretroviral therapy (HAART). Objective: To determine the relationship between the pharmacological aspects and adherence to antiretroviral treatment in a Colombian IPS. Methodology: Cross-sectional analytical study in patients with HIV on antiretroviral treatment between 2012 and 2020. A multiple binary logistic regression model was used for explanatory purposes. Results: A total of 9,835 patients were analyzed where the proportion of adherence was 90 % and in the adjusted model its relationship with history of non-adherence was assessed (ORa: 0,52 95 % CI: 0,40-0,66), pharmacological group (2 NRTI + 1 PI or other) (ORa: 1,22 95 % CI: 0,99-1,76), two doses per day (ORa: 1,02 95 % CI: 0,74-1,40), units per day (≥ 3 ) (ORa: 0,69 95 % CI: 0,47-1,02), adverse drug reactions (ORa: 0,56 95 % CI: 0,40-0,78), polypharmacy (ORa: 1,36 95 % CI : 1,00-1,85), ART time (1 to 2 years) (ORa: 1,63 95 % CI: 1,27-2,09), ART time (6 to 12 months) (ORa: 1,66 95 % CI: 1,27-2,18), ART time (<6 months) (ORa: 1,36 95 % CI: 1,03-1,78), inconsistency in the claim (ORa: 0,42 95 % CI: 0,32-0,55) and PRUM history (ORa: 0,11 95 % CI: 0,09-0,14). Discussion: The proportion of adherence obtained is higher than that described for other countries (between 60-77 %); however, the findings corresponding to the effect of the pharmacological variables analysed are in line with those described in previous studies on the subject. Conclusion: The history of non-adherence, adverse reactions, inconsistencies in the claim fill history and problems related to the use of medications are aspects that reduce the probability of adherence. While the longer time of use of the treatment increases adherence.

Metabolic adverse drug reactions in geriatric patients in Odisha

Background: Geriatric patients are at a greater risk of developing adverse drug reaction (ADR) because of changed metabolic activity and renal status associated with aging. As most of the elderly patients suffer from multiple chronic diseases (Diabetes, Hypertension, Arthritis, constipation, peptic ulcer disease, etc.), they are under polypharmacy and the risk of ADRs is exacerbated by multiple medications. Metabolic ADRs include weight gain, hypoglycemia, hyponatremia, hypokalemia, and the endocrinal abnormality are the frequent cause of hospital admission in geriatric patients. Most metabolic ADRs due to drugs are treatable. There are few such studies conducted in India regarding metabolic ADR in geriatric patients. Hence, this study aims to evaluate the metabolic ADRs encountered in geriatric patients with the following objectives in Odisha. Aim and Objectives: The prevalence and spectrum of metabolic ADRs in geriatric population were studied. The causality assessment, severity assessment, and preventability were done using standard scales. Materials and Method: This was a prospective and observational study conducted from September 2016 to September 2018 in Department of Pharmacology in collaboration with Department of Geriatric Medicine and Department of Medicine of SCB Medical College and Hospital. All geriatric patients (?60 years) with ADR, reporting to the above departments, were included in the study. The detailed information of type of ADRs and its characteristics was filled up in Suspected ADR Reporting Form designed by Indian pharmacopeia commission version 1.3. The incidence and spectrum of metabolic ADRs were observed. Their causality, severity, and preventability were evaluated by the WHO-UMC System, Hartwig’s Severity Scale, and Schumock Thornton Preventability Scale, respectively. Result: A total of 236 ADRs were reported in 2 years, out of which 28.8% were metabolic ADRs. Metabolic ADRs were more reported in young old patients and often encountered ADR was hypoglycemia 73.5% due to use of oral anti diabetics. About 29% of the metabolic ADRs had a causal relation of probable association. About 94.2% were moderate in severity and 89.7% metabolic ADRs could be probably preventable. Conclusion: There was a probable causal association of metabolic ADR with the drug used and they were moderate verity. The metabolic ADRs found in our study can be preventable with appropriate means.

Retrospective study on cutaneous adverse drug reactions in a tertiary care center

Background: Cutaneous adverse drug reactions (CADRs) range from mild-to-severe types and occasionally can become fatal. Hence, these incur additional financial burden both to patients and community. Aim and Objective: The aim of the study was to describe the characteristics of CADRs reported to ADR monitoring center (AMC) of a tertiary care center. Materials and Methods: CADRs reported to the AMC over a period of 2 ½ years were retrospectively studied. This study mainly focused on affected age group, gender, various pattern of CADRs, the group and name of drugs causing CADRs, and severity and causality assessment. Results: CADRs contributed 31.6% of the total ADRs reported to the AMC. Among these, 51.7% were females and 40% were of 51–60 years age group. About 37.9% of CADRs were pruritus. Antibacterial drugs were the most common cause of CADRs and beta-lactam antibiotics were responsible for 30% of CADRs. Stevens Johnson syndrome (SJS) constituted 4.9% of CADRs and 20% of this was due to Paracetamol. Drugs were withdrawn in 89% of cases and 85% cases recovered. On causality assessment, 94% were of probable category. Conclusion: Pruritus was the most commonly observed CADR and antibacterial drugs were the most common cause. Beta lactam antibiotic was the most frequent antibacterial drug to cause CADRs. The most common serious CADR was SJS and Paracetamol was the most frequent culprit drug.

Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

PHARMACOVIGILANCE IN INDIA: PAST, PRESENT, AND FUTURE PERSPECTIVE

Its start a decade ago, pharmacovigilance (PV) experienced tremendous development. There have been significant attempts in recent years to transform the current pharmacovigilance systems to meet future expectations. Adverse drug reactions (ADRs) are increasing in frequency, severity, and complexity as novel medication therapies are coming to market more quickly as a result of better laws and regulations. India is the second most popular nation in the world, with around 1 billion active and prospective consumers of pharmaceuticals. Despite being a member of the Uppsala Monitoring Centre, our nation has almost little commitment to the database. This problem is brought on by the inadequate ADR (adverse drug reaction) monitoring system and lack of knowledge among pharmacy associates and medical professionals. The primary objectives of the PV program are patient care, patient safety, and monitoring of negative medication reactions. There is a need for additional clinical preliminary exams and clinical assessments in India to accurately practice PV. A fully functional PV system is essential for the safe and responsible administration of medicines. This review gives a systematic review of pharmacovigilance in India from its origin to its current scenario and also discusses the various strategies and proposals to build, maintain and implement a robust pharmacovigilance system for India in coming years.

Self-assumed Neurologic Related Condition Deviated Metoclopramide-Induced Acute Dystonic of Oculogyric Crisis in a Woman of Childbearing Age: A Case Report

A 26-year-old Malaysian woman (childbearing age) attended a private primary care clinic with a known case of gastroesophageal reflux disease (GERD) and complained of persistent nausea and a few episodes of vomiting. She had no known drug allergy, no surgical history, no hospitalization in the last two years, was a non-smoker, and no history of drug or alcohol abuse. The patient was prescribed Tab metoclopramide 10 mg TDS and Tab ranitidine 150 mg BD for five days. About 30 min after oral administration of both medicines, her eyes rolled involuntary upward, leading to lateral deviation of the eyes, and mouth jaws clenched as if “dislocated jaws.” The patient was immediately brought into an emergency department (ED) of a public tertiary care hospital. A drug challenge test was done which resulted in the withdrawal of metoclopramide. The accompanied sister later disclosed that the patient had taken metoclopramide and ranitidine from a private clinic earlier in the day. The patient self-assumed to have a sudden seizure, due to excessive hot weather and dehydration. A slow intravenous infusion of 50 mg/mL diphenhydramine hydrochloride in 0.9% w/v NaCl 100 mL was administered stat. Consequently, the symptoms vanished after approximately 30 min of the therapy, devoid of relapse. The patient was discharged from ED post 8 hours of monitoring with complete recovery. Physicians frequently prescribe metoclopramide to treat nausea and vomiting, which may cause adverse drug reaction of acute dystonic oculogyric crisis (OGC). Due to its unwanted and unpredictable extrapyramidal symptoms, metoclopramide should be prescribed and dispensed with caution. Thorough history taking at ED is imperative for correct early diagnosis and treatment, as metoclopramide-induced dystonic OGC has a high probability of confusion with other causes of dystonia such as conversion and seizures, encephalitis, tetanus, and hypercalcemic tetany.

Retrospective study on the use of epinephrine in patients with drug-induced anaphylactic shock in Chongqing from 2015 to 2022 / 中国药房

OBJECTIVE To evaluate the rationality of epinephrine in the treatment of drug-induced anaphylactic shock， and to provide a reference for further standardizing the treatment measures of anaphylactic shock. METHODS According to the relevant data of the reports of severe adverse drug reaction （ADR） of drug-induced anaphylactic shock provided by Chongqing ADR Monitoring Center from 2015 to 2022， the selection of treatment drugs， and the application of epinephrine in anaphylactic shock were analyzed retrospectively； the clinical outcomes of anaphylactic shock with different epinephrine administration methods were investigated. RESULTS A total of 1 415 cases of severe ADR related to drug-induced anaphylactic shock were reported， with a male-to-female ratio of 1.04∶1； the drugs that caused allergic shock mainly included anti-infective drugs （47.92%）， TCM injections （9.12%）； the patients who suffered from drug-induced anaphylactic shock within 10 min after medication accounted for 43.96%； 97.24% of patients were cured or improved， and 2.76% of patients died or did not been improved. Among 1 415 patients， 63.39% of patients were treated with epinephrine， and the patients who preferred epinephrine treatment accounted for 53.14%； the intramuscular injection， subcutaneous injection， intravenous injection and intravenous drip accounted for 33.78%， 30.32%， 25.75% and 1.23%， respectively. The initial dose range of epinephrine was 0.01-10 mg， and the most frequent single dose was 1 mg （44.70%）. Excessive single doses of intramuscular injection， subcutaneous injection and intravenous injection accounted for 51.03% （148 cases）， 53.13% （136 cases） and 91.47% （193 cases） respectively， and the risk of overdose in intravenous injection was higher （P＜0.05）. The patients receiving initial treatment with epinephrine had a higher improvement rate/cure rate than those who did not use epinephrine （98.14% vs. 96.23%， P＝0.029）； the patients who preferred epinephrine had a higher improvement rate/cure rate than those who did not preferred epinephrine （98.14% vs. 95.17%， P＝0.031）； the improvement rate/cure rate of patients receiving intramuscular injection of epinephrine was higher than those without intramuscular injection （99.01% vs. 96.69%， P＝0.038）. CONCLUSIONS There are some unreasonable phenomena in the treatment of drug-induced anaphylactic shock， such as inappropriate selection of drugs， insufficient use of epinephrine， delay of administration， inappropriate route of administration and excessive single dose.

Efficacy of perioperative use of tigecycline in preventing infection and incidence of hypofibrinogenemia in liver transplant recipients / 器官移植

Objective To evaluate the efficacy of perioperative use of tigecycline in preventing infection and the incidence of hypofibrinogenemia in liver transplant recipients. Methods Clinical data of 40 liver transplant recipients given with tigecycline to prevent infection were retrospectively analyzed. The incidence of infection in recipients and donor-derived infection were analyzed. The changes of clinical indexes in recipients during, upon the completion and (7±2) d after tigecycline treatment were analyzed, respectively. The incidence and treatment of hypofibrinogenemia were summarized. Results Among 40 liver transplant recipients, 2 cases were infected by aspergillus niger and cytomegalovirus, out of the antibacterial spectrum of tigecycline. After adjusting the anti-infection regimen, the infection was properly controlled. Liver allografts were positive for relevant culture in 9 cases, whereas none of them progressed into donor-derived infection. Approximately at postoperative 2 weeks, all 40 recipients restored liver function and were discharged from hospital. Among them, 6 recipients developed hypofibrinogenemia complicated with coagulation disorder at postoperative 2-4 d, whereas transaminase level, bilirubin level and infection-related indexes were gradually decreased after liver transplantation, and albumin level was stable. After supplemented with human fibrinogen and prothrombin complex, coagulation function was improved, but fibrinogen level persistently declined. After terminating use of tigecycline, fibrinogen level was gradually restored to normal range, which might be an adverse drug reaction induced by tigecycline. Conclusions Perioperative anti-infection regimen including tigecycline may reduce the incidence of infection caused by sensitive bacteria in liver transplant recipients. Nevertheless, the incidence of hypofibrinogenemia should be intimately monitored throughout the use of tigecycline.

Analysis of influential factors for blood concentrations and adverse drug reaction in the treatment of lymphoma with high-dose methotrexate / 中国药房

OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate （HD-MTX） and the occurrence of adverse drug reactions （ADR） when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021， the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis， such as medical record number， age， sex， height， body mass， chemotherapy plan， dosage； test indexes such as alanine transaminase， aspartate transaminase， total bilirubin， creatinine clearance （CrCl）， albumin （ALB） and other indexes were also collected before and after administration. The blood concentrations （c6 h， c24 h， c48 h） of HD-MTX were recorded， drug information of proton pump inhibitors （PPIs） was extracted and used， and ADR occurring within 48 h after administration were all evaluated. Single factor analysis， multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age， CrCl had an effect on c 6 h （P＜0.05）； age， CrCl and ALB had an effect on c24 h （P＜0.05）； age， body mass index （BMI）， CrCl， combined use of PPIs and ALB had an effect on c48 h （P＜0.05）. The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h （P＞0.05）， age was the main influential factor of c 24 h （P＜0.05）， and CrCl and combined use of PPIs were the main influential factors of c48 h （P＜0.05）； the coefficient of variance expansion was between 1 and 3.5， indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%， of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age， BMI， liver function and CrCl had effect on the incidence of ADR （P＜0.05）. CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma， the patient’s age， CrCl and combined use of PPIs should be considered， and the patient’s blood concentration should be monitored； at the same time， the age of patients， BMI， liver function and CrCl have an impact on the incidence of ADR.

Literature analysis of lung toxicity related to cyclin-dependent kinase 4/6 inhibitors / 中国药房

OBJECTIVE To provide reference for rational use of cyclin-dependent kinase 4/6 （CDK4/6） inhibitors. METHODS Retrieved from Web of Science， PubMed， SpringerLink， CNKI， Wanfang Data and VIP database， and so on， the literature about lung toxicity related to CDK4/6 inhibitors were collected and analyzed statistically with Excel 2013 software. RESULTS A total of 12 literature which met the inclusion and exclusion criteria were included； 13 patients were involved， among which 3 cases were from the United States， 3 from Japan， 2 from India， and 1 from Israel， Spain， France， Australia and Saudi Arabia respectively； all patients were female， aged between 43-89 years， of whom 8 were treated with palbocicilib， 3 with abemacilib， and 2 with ribociclib. The lung toxicity of patients after medication occurred from 1 week to 15 months； the majority of patients were hospitalized with the symptom such as difficulty breathing， chest tightness， shortness of breath， dry cough， etc. The lung toxicity mainly manifested as interstitial lung disease， eosinophilic pneumonia， mediastinal and pulmonary granulomatous reaction， drug-induced pneumonia， diffuse alveolar damage， organizing pneumonia and so on. The shortest treatment duration was 3 weeks， and the longest was 6 months. The treatment measures included drug withdrawal， intravenous use of antibiotics， intravenous use of systemic steroids， oxygen inhalation， and so on； after treatment， 8 patients improved or recovered， and 5 patients died due to deterioration. One patient developed lung toxicity again after reuse of such drugs and must stop drugs permanently. CONCLUSIONS Lung toxicity related to CDK4/6 inhibitors possibly cause mortality. It is necessary to make early judgment， stop the drug in time， and give patients systemic steroids， oxygen inhalation and other treatment measures as soon as possible.

Mining and analysis of risperidone adverse event signals based on FAERS database / 中国药房

OBJECTIVE To provide reference for safe use of risperidone in clinic. METHODS Data mining and analysis of risperidone-related adverse drug event （ADE） reports from the first quarter of 2017 to the third quarter of 2021 in the United States FAERS database were carried out using reported odds ratio and composite criteria methods from Medicines and Healthcare Products Regulatory Agency. RESULTS There were 101 181 ADE reports with risperidone as the primary suspect drug，involving a total of 33 179 patients. Among those reports，the male-to-female ratio was about 6.21 to 1； most of them were ＜18 years old （15.01%）； ADE was mainly reported by consumers （69.74%） and mainly reported by the United States （79.72%）； oral dosage form was the most used，accounting for 83.71%. A total of 409 ADE signals were obtained，including male breast development， pseudogynecomastia，abnormal increase in body mass，hyperprolactinemia and Wellens syndrome，etc. Twenty-six systems and organs were involved，mainly including reproductive system and breast diseases，various injuries，poisoning and operational complications， mental diseases，metabolic and nutritional diseases，and various nervous system diseases，etc. CONCLUSIONS The common ADE signals of risperidone and the system involved are consistent with the instructions，but we should also be alert to the ADE not recorded in the instruction，such as Wellens syndrome，fibroproliferative endocarditis，cavernous degeneration of portal vein，rabbit syndrome，etc.

Pyogenic granuloma of the gums and lips caused by camrelizumab: case report and literature review / 口腔疾病防治

Objective@# To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. @*Methods@# A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. @*Results@# After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible.@*Conclusion @#Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.

Literature analysis of ocular adverse drug reactions related to dupilumab / 中国药房

OBJECTIVE To analyze the clinical manifestation and characteristics of ocular adverse drug reaction （ADR） related to dupilumab， so as to provide reference for clinically safe drug use. METHODS Retrieved from CNKI， Wanfang data， VIP and PubMed databases， the case reports about ocular ADR caused by dupilumab were collected， and then analyzed statistically in terms of gender， age， primary disease， drug use， occurrence time of ADR， main clinical manifestations， treatment or outcome， etc. RESULTS A total of 20 pieces of literature were selected， involving 46 patients， among which there were 29 males and 17 females. Mainly patients were under 60 years old. The results of the association evaluation was given as follows： 13 were “very likely” and 33 were “likely”. All patients were treated with dupilumab for atopic dermatitis （AD） without off-label medication. The occurrence time of ADR was 2 weeks to 2 years after administration， mainly within 6 months after medication. All patients received dupilumab monotherapy except that 3 patients with hypertension and 1 patient with chronic obstructive pulmonary disease and human immunodeficiency virus received other drugs simultaneously. Twenty-eight patients had a history of allergic disease， and 11 patients had a history of eye disease. Ocular ADRs were mainly conjunctivitis and uveitis， and the clinical manifestations mainly included conjunctival congestion， swelling， eye secretions， etc. Ten patients developed severe ADR， including uveitis， severe conjunctivitis， and tear point stenosis； 45 patients were improved after symptomatic treatment. AD， serious initial symptoms of AD， allergic disease and underlying ocular diseases might be the high-risk factors of ocular ADR caused by dupilumab. CONCLUSIONS Whether the patient has the history of allergic diseases and basic eye diseases should be asked in detail before clinical use of dupilumab. When using the drug， attention should be paid to monitoring whether the patient has intraocular inflammation， be alert to the occurrence of new or serious ADR， and give timely symptomatic treatment to ensure the safety of drug use.

Literature analysis of sunitinib-induced nephrotic syndrome / 中国药房

OBJECTIVE To analyze the clinical characteristics of nephrotic syndrome induced by sunitinib， and to provide reference for clinical rational drug use. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， Web of Science and Medline， case report about sunitinib-induced nephrotic syndrome were collected from the inception to Oct. 30th， 2022. Those case reports were analyzed statistically in terms of gender， age， primary disease， drug use， clinical manifestations， treatment and outcome. RESULTS A total of 15 pieces of literature were collected and 17 patients were involved， including 10 males and 7 females. The average age of patients was （59.35±15.72） years. Among 17 patients， there were 10 patients with renal cell carcinoma and 7 patients with gastrointestinal stromal tumor， all of whom received evidence-based medication； the dosage of sunitinib in 15 cases was recorded， and all of them were within the recommended range of the instructions； 9 patients received combined therapy； the time from sunitinib application to the occurrence of nephrotic syndrome was 21 days-52 months， of which 11 cases were ≤2 years. The clinical manifestations in 13 patients were described， including edema， oliguria， foamy urine， weight gain， fatigue， dyspnea on exertion， etc. Eight patients had other adverse reactions induced by sunitinib before suffering from nephrotic syndrome， including new hypertension or worsening of original hypertension， and hand-foot syndrome. Renal biopsy mainly manifested as thrombotic microangiopathy， focal segmental glomerular sclerosis and immune complex glomerulonephritis. Sunitinib withdrawal or dosage reduction was adopted in all patients， and they were given symptomatic treatment such as glucocorticoids and antihypertensive agents. Symptoms of 16 patients were improved， and renal function of one patient deteriorated and hemodialysis was started. Sunitinib was re-challenged in 6 patients， elevated creatinine and substantial proteinuria recurred in 5 patients. CONCLUSIONS In clinical use of sunitinib， it is advisable to periodically monitor renal function. In case of deterioration of renal function， albuminuria， edema， etc.， relevant examinations should be implemented in time， and symptomatic intervention should be taken as soon as possible. Besides， we should be alert to the recurrence of nephrotic syndrome after sunitinib rechallenge.

A case analysis of acute-on-chronic liver failure caused by abiraterone / 中国药房

Abiraterone is commonly used as a targeted drug for the treatment of prostate cancer， which commonly causes adverse drug reactions （ADR）， including abnormal liver function， fatigue， nausea and edema， etc. This study reports a 78-year-old man with a history of hepatitis B and liver cirrhosis after prostate cancer resection who was admitted to the First Affiliated Hospital of Henan University of Chinese Medicine. The patient received abiraterone treatment 1 month before admission and developed gastrointestinal symptoms 3 weeks after the treatment and worsened at 4th week with yellowing of the skin， sclera and urine. Unfortunately， the patient died after 5 weeks of abiraterone treatment （1 week after admission）. Based on test and examination results， the patient was diagnosed with acute-on-chronic liver failure （ACLF）. This paper analyzes the patient’s medical history and the relevant treatment in detail. It is evaluated that ACLF and abiraterone are “probably” related based on Naranjo ADR Probability Scale， suggesting abiraterone may induce severe ADR of liver failure in patients with chronic liver diseases such as cirrhosis. These patients should be monitored dynamically for changes in liver function and treated prophylactically with liver-protective drugs if necessary.

Mining and analysis of the ADE signals of avapritinib based on FAERS database / 中国药房

OBJECTIVE To provide reference for clinically safe application of avapritinib. METHODS The adverse drug event （ADE） reports of avapritinib from January 9th，2020，to September 30th，2022 were collected from FDA Adverse Event Reporting System （FAERS） database. For data mining and analysis，reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method in the proportional imbalance method were utilized. RESULTS A total of 10 895 ADE reports with avapritinib as the main suspect drug were gathered，and 201 ADE signals involving 19 systematic organ classifications were found after eliminating invalid signals. The instruction of the drugs did not mention any of the ADE，including tinnitus，dementia，chilly limbs， the reduction of blood iron，the reduction of blood sugar，fever，the reduction of vitamin D and vitamin B12，as well as all ADE in the 2 SOCs of musculoskeletal and connective tissue illnesses，diseases of the reproductive system，and diseases of the breast. The majority of the ADE reports 670 cases with complete drug information were for the nervous system （230 cases，accounting for 34.33%） and ocular organ （277 cases，accounting for 41.34%）. Compared with other systems，daily dose and treatment course showed significant effects on ADE of neurological system and ocular organ （P＜0.05），and the patient’s age had a significant impact on the ADE of the nervous system （P＜0.05）. CONCLUSIONS A greater incidence of ADE after using avapritinib is present in patients older than 65 with a daily dose of 300 mg/d and a treatment period lasting between 31 and 90 days； patients receiving a daily dose of 300 mg/d and a treatment regimen lasting 31 to 90 days are more likely to experience ADE of the ocular organ. Attention should be given to the aberrant symptoms of the patient’s eyes and nervous system throughout clinical use of avapritinib，and prompt intervention should be given.

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.

Mining and analysis of adverse drug event signals related to mepolizumab / 中国药房

OBJECTIVE To provide reference for rational clinical use of mepolizumab. METHODS The reporting odds ratio method and Bayesian confidence propagation neural network method were used to conduct signal mining and analysis of adverse drug event （ADE） reports related to mepolizumab in the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2016 to the third quarter of 2022. RESULTS A total of 57 501 ADE reports were extracted with mepolizumab as the primary suspect drug， involving 16 358 patients. Among these reports， the proportion of males （23.51%） was lower than females （50.48%）. The reporting countries were primarily the United States （51.91%） and Canada （29.94%）. Consumers （71.18%） constituted the main reporting population. A total of 172 ADE-positive signals were identified， mainly involving 13 system organ classes such as the respiratory， thoracic and mediastinal disorders （41.63%）， as well as infectious and parasitic diseases （14.16%）. There were 60 high-risk signals， including 15 that were explicitly mentioned or related to adverse reactions in the drug instructions of mepolizumab and 45 signals （such as asthmatic crisis， sputum discoloured， purulent sputum， sleep disorder due to a general medical condition） were newly identified high-risk signals. Among them， 11 high-risk signals exhibited gender or age differences. CONCLUSIONS When clinically using mepolizumab， in addition to the adverse reactions mentioned in the drug instruction， special attention should also be given to changes in the nature of sputum， painful respiration， and sleep disorders.

Literature analysis of adverse drug reactions induced by dronedarone / 中国药房

OBJECTIVE To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR） induced by dronedarone，and to provide reference for clinically safe drug use. METHODS Retrieved from PubMed database， Wanfang database，CNKI and VIP （up to August 31st， 2022），ADR cases of dronedarone were analyzed retrospectively in respect of patient’s age，gender，nationality，usage and dosage of dronedarone，and occurrence time，clinical manifestations，treatment measures and outcome of ADR，etc. RESULTS A total of 26 case reports were included，with a total of 27 patients. The age of the patients was 41-86 years old，with an average age of 68.8 years. The proportion of patients aged 60-79 was the largest （20 cases，74.1%）. There was no significant difference in the number of males （14 cases） and females （13 cases）. The patients came from 6 countries， of which the United States was the largest （16 cases，59.3%）. The dosage of 14 patients was 400 mg bid；one patient was 200 mg bid；the dosage for 12 patients was not specified. The most ADR cases （16 cases，59.3%） occurred within 1 month，of which 11 cases（40.7%） occurred within 1 week，and there were no ADR reports with medication more than 12 months. Organs/systems involved in ADRs were mainly liver and biliary diseases （7 case times，23.3%），skin and subcutaneous tissue diseases （6 case times， 20.0%），respiratory tract，thoracic and mediastinal diseases （5 case times，16.7%）. In addition，ADR also occurred in heart diseases， kidney and urinary system diseases，vascular diseases，medical examinations and eye diseases. Among 27 patients，there were 3 cases of death，the ADR were bronchiolitis obliterans with organizing pneumonia，toxic epidermal necrolysis and hepatic failure， respectively. One patient underwent liver transplantation. CONCLUSIONS Dronedarone can cause multiple organ system ADR. Before use，it is necessary to improve the examination including ECG，liver function，lung function，etc. and strengthen drug use monitoring within one month after the start of use，especially the ADR of hepatobiliary，skin and respiratory system. The occurrence of severe ADR has no obvious relationship with the duration of medication； even if it is taken safely for a long time，it still needs continuous pharmaceutical monitoring and follow-up to ensure the clinical medication safety of patients.

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-alcoholic steatohepatitis (NASH) causes disease-specific alterations to the absorption, distribution, metabolism, and excretion (ADME) processes, including a decrease in protein expression of basolateral uptake transporters, an increase in efflux transporters, and modifications to enzyme activity. This can result in increased drug exposure and adverse drug reactions (ADRs). Our goal was to predict drugs that pose increased risks for ADRs in NASH patients. Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease, mainly non-alcoholic fatty liver disease (NAFLD), 54 of which are known substrates of transporters and/or metabolizing enzymes. Since NASH is the progressive form of NAFLD but is most frequently undiagnosed, we identified other drugs at risk based on NASH-specific alterations to ADME processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients, especially when eliminated through multiple pathways altered by the disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients.