Análisis de reacciones adversas a medicamentos por fármacos antipsicóticos en un instituto de salud mexicano / Analysis of adverse drug reactions caused by antipsychotic drugs in a mexican health institute

RESUMEN Introducción: Las reacciones adversas a medicamentos (RAM) son manifestaciones clínicas o de laboratorio no deseadas que se relacionan con el consumo de medicamentos. Las RAM se asocian con un riesgo significativo de morbimortalidad e ingresos hospitalarios. Los antipsicóticos poseen una reducida ventana terapéutica y se han relacionado con la manifestación de una diversidad de RAM. Objetivo: Evaluar el patrón de las RAM debido a fármacos antipsicóticos, detectadas en pacientes atendidos en el Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz entre diciembre de 2021 y mayo de 2022. Métodos: Estudio observacional, descriptivo, prospectivo y transversal de una serie de casos. La gravedad, la severidad y la calidad de la información de la notificación de las RAM se definieron conforme a la NOM-220-SSA1-2016, instalación y operación de la farmacovigilancia, mientras que la causalidad se determinó mediante el algoritmo de Naranjo. Resultados: La incidencia de las RAM fue del 59% y se detectó una o más RAM en 52 de los 88 pacientes que estaban en tratamiento antipsicótico durante el periodo de estudio. El 45% de las RAM tuvo una causalidad probable y el 55%, posible; únicamente tres RAM se clasificaron como graves, debido a que prolongaron la estancia hospitalaria y pusieron en peligro la vida del paciente. Conclusiones: Las RAM de los sistemas gastrointestinal y endocrino fueron las más incidentes, y la hiperprolactinemia fue la más frecuente. La olanzapina y clozapina fueron los medicamentos que más RAM provocaron. Se recomienda fomentar la cultura de notificación y seguimiento de RAM causadas por fármacos antipsicóticos.

ABSTRACT Introduction: Adverse Drug Reactions (ADR) are unwanted clinical or laboratory manifestations that are related to drug use. ADR are common and are associated with significant risk of morbidity, mortality and hospital admissions. Antipsychotics have a reduced therapeutic window, and have been related to the manifestation of a variety of ADR. Objetive: To evaluate the pattern of ADRs due to antipsychotic drugs detected in patients treated at the Ramón de la Fuente Muñiz National Institute of Psychiatry between December 2021 and May 2022. Methods: Observational, descriptive, prospective and cross-sectional study of a series of cases. The seriousness, severity, and quality of the information in the notification of the ADR were defined in accordance with NOM-220-SSA1-2016, Installation and Operation of Pharmacovigilance, while causality was determined using the Naranjo algorithm. Results: The incidence of ADRs was 59%, with one or more ADR detected in 52 of the 88 patients who were receiving antipsychotic treatment during the study period. Forty-five percent of the ADR had probable causality and 55% possible; only three ADR were classified as serious as they prolonged the hospital stay and endangered the patient's life. Conclusions: The ADR of the gastrointestinal and endocrine systems were the most incidental, with hyperprolactinemia being the most frequent. Olanzapine and clozapine were the medications that caused the most ADR. It is recommended to promote the culture of notification and follow-up of ADR caused by antipsychotic drugs.

When the fever will not stop, stop the pills! A case report

ABSTRACT Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

Analysis of medical disputes related to drug-induced cross-allergy and study on prescripition review strategy / 药物流行病学杂志

Objective To analyze the rules and characteristics of cross-allergy cases related to drug-related medical disputes,and to provide reference for the formulation of cross-allergy prescription review strategy.Methods The judgments of cross-allergy related medical damage liability disputes recorded in the legal document database of Beijing Yingke Law Firm and the Chinese Judgment Document Network database from August 2010 to June 2023 were analyzed,the causes of relevant disputes were summarized and analyzed,and more comprehensive response measures were formulated.Results A total of 65 judgments were retrieved,and seven judgments were included.The main drugs causing cross allergy were antibiotics(penicillins,cephalosporins and sulfonamides).Seven cases of medical disputes,all of which were ruled by the court that the medical party had medical errors due to cross-allergies,and had to bear 30％to 80％of the compensation liability.The main reasons for the punishment were that the doctor did not pay enough attention to the patient's past history of allergy and chose unreasonable drugs.Conclusion Medical institutions can reduce the risk of cross-allergy by means of information technology,and play the role of pharmacists in prescription review and pharmaceutical care.Physicians should pay attention to the patient's past history,earnly inquire,strengthen medication education and monitoring,reduce the threat of adverse reactions to the patient's life safety and related drug disputes,and protect the legitimate rights and interests of both doctors and patients.

A case of toxic epidermal necrolysis caused by sorafenib and sintilimab / 药物流行病学杂志

A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30％of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.

A case of temporomandibular joint dislocation caused by rosuvastatin calcium tablets / 药物流行病学杂志

A 50-year-old female presented with bilateral cervical arteriosclerosis and right-sided plaque formation,after 25 d of treatment with rosuvastatin calcium tablets(20 mg,po,qn),the patient developed temporomandibular joint dislocation,the adverse reactions occurred again after giving manipulative repositioning.The patients were healthy,had no history of trauma and related diseases in stomatology,no history of drug allergy,patients did not open their mouth loudly at the onset of the disease,no external factors affecting the use of drugs during the combined use of other drugs.It was considered"very likely"that the dislocation of the jaw joint was caused by rosuvastatin calcium tablets.The patients were followed up for 3 months after the treatment of manipulative repositioning and other treatments,did not have any further dislocation of the temporomandibular joint dislocation.It is suggested that when using rosuvastatin calcium in clinical practice,attention should be paid to strengthening drug observation to ensure drug safety.

Pharmaceutical care for a patient with paroxysmal spasms of extremities caused by ceftazidime-avibactam / 中国药房

OBJECTIVE To explore the role of clinical pharmacists in identifying paroxysmal spasms caused by drugs， and provide reference for rational drug use. METHODS Retrospective analysis was conducted on pharmaceutical care provided by clinical pharmacists for a patient with ceftazidime-avibactam （CZA-AVI） induced paroxysmal spasms. The clinical pharmacists identified， analyzed and summarized the clinical manifestations， risk factors and treatment methods of the nervous system toxicity caused by antibacterial drugs. According to the patient’s clinical symptoms and test results， the clinical pharmacists recommended temporarily discontinuing the use of polymyxin B and montelukast sodium， and halving the dose of CZA-AVI. The physicians did not adopt the recommendation to halve the dose of CZA-AVI， and when the patient’s neurologic toxicity did not improve， the clinical pharmacists again recommended discontinuing CZA-AVI， which was accepted by the physicians. RESULTS Clinical pharmacists analyzed the condition and checked related drugs that caused paroxysmal spasms of extremities one by one， and finally determined that CZA-AVI might be the drug that caused paroxysmal spasms of extremities in the patient. After stopping the drug， the patient’s symptoms improved and was transferred to a community hospital for rehabilitation treatment. CONCLUSIONS The dose of CZA-AVI should be adjusted according to the renal function and the neurotoxicity should be guarded against， especially for patients with advanced age， renal insufficiency， and the combined use of multiple drugs related to nephrotoxicity and neurotoxicity.

Retrospective analysis of adverse drug reactions of bevacizumab biosimilar and original drug in our hospital / 中国药房

OBJECTIVE To analyze the occurrence of adverse drug reactions （ADR） between bevacizumab biosimilars and original drugs， and to provide data support for rational use of drugs in clinical. METHODS ADR reports of bevacizumab biosimilars and original drugs reported by Jiangsu Cancer Hospital from January to December 2022 were retrospectively analyzed. RESULTS A total of 6 818 patients were treated with bevacizumab， and 136 ADR patients were reported. The incidence of ADR caused by bevacizumab biosimilars was higher than original drugs （2.18% vs. 0.71%， P＝0.004）. In ADR reports， the main treatment plan was bevacizumab combined with other tumor drugs （129 patients）； 118 patients were cured and improved； there were 108 general reports and 28 serious reports； the main system/organ involved in ADR was the cardiovascular system； there were no statistical significance in the incidence rates of hypertension/blood pressure increase， leukocyte/platelet decrease， diarrhea and fever caused by bevacizumab biosimilars and original drugs. CONCLUSIONS The incidence of ADR related to bevacizumab biosimilars is significantly higher than that of the original drugs， but there is no significant difference in the clinical manifestation of ADR. Clinicians can use bevacizumab biosimilars or original drugs based on the willingness of patients and their families.

Research progress of chemotherapy-related diarrhea induced by molecularly targeted anti-tumor drugs / 中国药房

Diarrhea caused by chemotherapy is called chemotherapy-related diarrhea （CRD）. CRD can lead to reduced treatment effectiveness and compliance， affect the long-term outcome of tumor patients， and can be life-threatening in severe cases. In addition to conventional chemotherapy drugs， many molecularly targeted drugs are also associated with CRD， including small molecule epidermal growth factor receptor （EGFR） inhibitors， anti-EGFR monoclonal antibodies， phosphoinositide 3-kinase inhibitors， small molecule inhibitors of vascular endothelial growth factor receptor， BCR-ABL1 and KIT inhibitors， human epidermal growth factor receptor 2 target inhibitors， cyclin-dependent protein kinase inhibitors， antibody-drug conjugates and other molecularly targeted drugs. The occurrence mechanism may be related to the intestinal mucosal injury or enteritis caused by molecularly targeted drugs. The clinical manifestations are increased stool frequency and/or loose imposition， and patients are often associated with excess hyperproduction and/or colic. The incidence of CRD varies with different drugs. Great importance should be attached to collecting medical history and differential diagnosis， actively intervening and conducting dynamic evaluation， strengthening patient education， and timely detecting and preventing the occurrence of intestinal toxicity.

Literature analysis of ADR after the listing of apatinib / 中国药房

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.

Data mining and analysis of oxaliplatin-related adverse events of nervous system / 中国药房

OBJECTIVE To provide reference for clinically safe drug use by mining oxaliplatin-related adverse drug events （ADE） of the nervous system. METHODS Oxaliplatin-related neurologic ADE data reported by the FDA adverse event reporting system （FAERS） between January 1st， 2004 and December 31st， 2022 were collected. The reporting odds ratio and proportional reporting ratio were used for data mining. The data were classified statistically by using systematic organ classification， high-level group term （HLGT） and preferred term （PT） in the MedDRA （version 26.0）. RESULTS A total of 7 266 cases of oxaliplatin- related ADE， which were classified as various neurological， were retrieved， and 100 PT were identified. Of these， fifty-seven PT were unspecified adverse reaction signals in the manual. Among these reports， males （46.85%） were more than females （42.98%）， the age of patients was 45-＜75 years （65.22%）， the number of reports was highest in Italy （16.32%）， and the severe type was hospitalization or prolonged hospitalization （38.16%）. The top 5 PT reports in the list of case number were peripheral neuropathy， paresthesia， neurotoxicity， loss of consciousness and dysarthria. The top 5 PT reports in the list of signal intensities were cold- induced paresthesia， neuromuscular rigidity， acute polyneuropathy， neuronal neuropathy， axonal and demyelinating polyneuropathy. A total of 13 HLGT were involved， with neurological diseases （not classified separately） having the highest number of signals （29）. CONCLUSIONS When using oxaliplatin in clinical practice， it is not only necessary to monitor the high incidence of acute and chronic peripheral neuropathy， but also to pay attention to the patient’s consciousness state and neurological symptoms. We should pay attention to the rare types of adverse reactions， such as guillain-barre syndrome， Lhermitte sign， posterior reversible encephalopathy syndrome， and hyperammoniacal encephalopathy， so as to ensure the safety of medication.

Consensus on whole-process pharmaceutical care for iodine contrast medium / 中国药房

OBJECTIVE To explore the whole-process pharmaceutical care model of iodine contrast medium and promote the rational clinical use of iodine contrast medium. METHODS Clinical Professional Committee on Rational Drug Use of China Medical Education Association and Expert Committee on Drug Evaluation and Clinical Research of Guangdong Pharmaceutical Association organized domestic experts to establish a working group on the Consensus on the whole-process pharmaceutical care for iodine contrast medium. The working group conducted literature searches， evidence-based analysis， and discussions on the development process， indications， contraindications， adverse drug reactions， drug interactions， drug use for special population， pharmaceutical care， and other key topics to summarize the content and process of the whole-process pharmaceutical care for iodine contrast medium. This consensus was ultimately formed. RESULTS The consensus on whole-process pharmaceutical care for iodine contrast medium included an evaluation of the patient， renal function， combined drug use， and hydration regimen before examination， the presence of contrast agent extravasation or suspected acute adverse reactions during examination， observation time points and follow-up after examination， and the presentation of specific work in each stage through pharmaceutical care flowchart. The medication monitoring record form was also formed to record the work situation. CONCLUSIONS The consensus has established a whole-process pharmaceutical care system for iodine contrast medium， providing scientific evidence for clinical physicians and nursing staff in the rational use of such special drugs， and also serving as a reference for pharmacists in providing related pharmaceutical care.

Pharmacovigilance: How aware are the prescribers?

Background: Adverse drug reactions (ADRs) is one of the important factors contributing to morbidity and mortality among patients and is a major public health burden. Spontaneous ADR reporting plays an important role in detection of ADRs, reducing their incidence and improving patient safety. India has one of the lowest ADR reporting rates in the world. Aim and Objective: The aim of the study was to assess the knowledge, attitude and practice (KAP) of doctors towards pharmacovigilance. Materials and Methods: A KAP questionnaire validated by subject experts was given to the doctors outside the teaching profession within 50 km of Government TD Medical College, Alappuzha, who consented to be a part of the study. The questions were structured to obtain the demographic details of the doctors, their KAP toward pharmacovigilance. No identifiable information regarding the participants was collected and the participants were assured of their confidentiality. A week’s time was given to the participants to answer the questions. Results: During the period of 1 year from June 2019 to May 2020, a total of 121 doctors responded to the questionnaire. The respondents aged from 26 to 67 years with the mean age being 37.31 ± 14.15 years. 94 (77.7%) thought that anyone could report an ADR while 16 (13.2%) thought that only doctors could report ADRs. Only 76 (62.8%) were aware of the existence of National Pharmacovigilance Centre in India. Ninety-eight (81%) did not know how to submit the ADR form to the nearest pharmacovigilance center. A vast majority 99 (81.8%) thought that ADRs to drugs of any system of medicine could be reported, while 20(16.5%) felt that only ADRs to modern medicines need to be reported. Among the factors discouraging doctors from reporting ADRs, lack of training to report an ADR 99 (81.8%) and lack of time during practice 83 (68.5%) were cited as the common reasons. A vast majority 116 (95.9%) had not received any formal training on ADR reporting and 114 (94.2%) opined that they would like to receive a formal training on the same. Conclusion: Doctors were largely aware of pharmacovigilance but had lack of KAP of reporting ADRs and filling up an ADR form. It emphasizes the need for regular mandatory education and training on ADR reporting among healthcare workers, and also the need to run continuous awareness campaigns on spontaneous reporting of ADRs to enhance reporting rate.

A study on the knowledge, attitude, and practice on adverse drug reactions and pharmacovigilance among nursing staff

Background: Lack of knowledge of pharmacovigilance and underreporting of adverse drug reaction (ADR) are worldwide problems of big concern. Gross underreporting of ADR in India led to increased hospital admissions, increase in length of hospital stay, and increase in healthcare cost burden. Aims and Objectives: This study was planned to assess knowledge, attitude, and practice on ADR and pharmacovigilance among nursing staff in Gandhi Medical College and Associated Hospitals, Bhopal Madhya Pradesh. Materials and Methods: A questionnaire-based, cross-sectional, and observational study was conducted among nursing staff in a tertiary care Centre. Data were collected in the form of a validated questionnaire comprised of 17 questions regarding knowledge, attitude, and practice of nursing staff toward ADR and Pharmacovigilance. Data were analysis by descriptive statistics and result was computed. Results: Around 33% of respondents were aware of Pharmacovigilance program of India and 99% of them had knowledge about main objective of pharmacovigilance. Out of total filled questionnaire received, only 12% nurses practiced reporting ADR. The major factor discouraging participants from reporting ADR was lack of time to report. The majority of nursing staff had a positive attitude toward awareness of pharmacovigilance and ADR reporting. Conclusion: Our study has shown that there is lack of correct knowledge regarding ADR reporting and pharmacovigilance among staff nurses. Although, the attitude toward ADR reporting was adequate, the actual practice of ADR reporting is unsatisfactory. Hence, it is essential to train staff nurses regarding pharmacovigilance and ADR reporting

Evaluation of adverse drug reactions in patients of schizophrenia in tertiary care teaching hospitals in Central India

Background: For decades, it has been observed that mental health is shrouded in stigma and discrimination. The scope, severity, and expense of impairment and costs to people, families, and societies are staggering. Mental illnesses are among the most frequent illnesses, affecting over a quarter of the population in any given year. According to national institute of mental health and neurosciences, Bangalore, the prevalence of schizophrenia has been considered as 4/1000 for all ages and both sexes. Aim and Objectives: The objectives of this study were to as follows: (1) To evaluate adverse drug reactions (ADRs) in patients with schizophrenia who received antipsychotic treatment and (2) to compare ADRs in typical versus atypical antipsychotic agents in schizophrenic patients. Materials and Methods: A total of 50 schizophrenic patients were enrolled for evaluating adverse effects to antipsychotic drugs. During the research, all ethical precautions were taken. All patients were followed up by medical history, history of drugs, and any severity of adverse drug reaction. Causality assessment was graded by Naranjo scale. Result: Among all of the antipsychotic drugs, risperidone (05%), quetiapine (04%), and aripiprazole (04%) have shown lowest propensity to cause serious adverse event. These drugs are most commonly prescribed drugs and are least likely to affect quality of life of patient. However, the risk of extrapyramidal symptoms is lower with olanzapine (05%) than haloperidol (34%) and even in case with risperidone at higher dose (20%). Although atypical antipsychotics such as olanzapine (46%) have shown maximum potential to produce metabolic side effect such as dyslipidemia and hyperglycemia compared to that of other antipsychotics. Conclusion: The most common adverse effects were found with typical and atypical antipsychotics such as weight gain, drowsiness, constipation, sedation, dyslipidemia, and hypotension.

DRESS, una reacción alérgica no mediada por IgE / DRESS, a Non-IgE Mediated Allergic Reaction

Resumen El síndrome de reacción a medicamentos con eosinofilia y síntomas sistémicos (DRESS, por sus siglas en inglés) es una respuesta de hipersensibilidad multisistémica poco frecuente inducida por uno o varios medicamentos que puede inducir una reacción adversa cutánea grave, la cual es difícil de diagnosticar y pone en peligro la vida del paciente si no es identificada y no se recibe tratamiento. Frecuentemente, se manifiesta como una erupción cutánea amplia, linfadenopatía, signos de afectación de órganos viscerales y alteraciones hematológicas, como leucocitosis, eosinofilia y, en ocasiones, linfocitosis atípica que se presentan de 2 a 8 semanas posterior a la administración del fármaco responsable. Los medicamentos responsables con mayor número de reportes son la fenitoína, la carbamazepina, el alopurinol y el abacavir. Se han identificado algunos alelos específicos del antígeno leucocitario humano (HLA) que se asocian a la hipersensibilidad de estos fármacos. La fisiopatología del síndrome de DRESS aún no se conoce por completo, generalmente se trata de una respuesta de hipersensibilidad mediada por células T, al interactuar con el receptor del complejo principal de histocompatibilidad en individuos con factores de susceptibilidad genética, como ocurre en otros cuadros de reacciones graves secundarias a la ingesta de fármacos. Los criterios del European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) son los más utilizados para su diagnóstico. El síndrome de hipersensibilidad inducido por fármacos (DiHS), el síndrome de Stevens-Johnson (SSJ), la necrólisis epidérmica tóxica (NET), y la pustulosis exantemática generalizada aguda (PEGA) deben considerarse ante cualquier exantema que aparezca posterior a la administración de cualquier fármaco. La terapia incluye la eliminación del agente causal lo antes posible, así como los corticosteroides sistémicos, los cuales son los pilares del tratamiento.. Los agentes ahorradores de esteroides, como la ciclosporina, las inmunoglobulinas intravenosas (IVIGs) y otros agentes inmunosupresores, se han utilizado con éxito para contribuir al tratamiento.

Abstract DRESS (drug reaction syndrome with eosinophilia and systemic symptoms) is a rare drug-induced multisystemic hypersensitivity response that can induce a severe cutaneous adverse reaction that is difficult to diagnose and treat. It frequently manifests as an extensive skin rash, systemic symptoms, lymphadenopathy, visceral organ involvement, and hematological alterations, mainly leukocytosis, eosinophilia, and sometimes atypical lymphocytosis that manifest 2 to 8 weeks after continuous administration of the responsible drug. The most prevalent drugs related with this syndrome are phenytoin, carbamazepine, allopurinol, and abacavir. Some specific human leukocyte antigen (HLA) alleles have been identified that are associated with hypersensitivity to these drugs. The pathophysiology of DRESS syndrome is not yet fully understood; the main hypothesis is a T-cell mediated hypersensitivity response when interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. The criteria of the European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) are the most commonly used for the diagnosis of DRESS syndrome. Drug-induced hypersensitivity syndrome (DiHS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) should be considered for any rash that appears following the administration of any drug. Therapy of DRESS includes the elimination of the causative agent as soon as possible, as well as systemic corticosteroids which are the cornerstones of treatment. Steroid-sparing agents such as cyclosporine, intravenous immunoglobulins (IVIGs), and other immunosuppressive agents have been used successfully to contribute to treatment.

Study of pattern and time-reaction sequence for adverse drug reactions reported to antiretroviral drugs

Background: Adverse drug reactions (ADRs) to antiretroviral drugs have a varied pattern and wide spectrum of severity from mild to very serious. The lack of a pre-established time-reaction sequence hampers the causality assessment of ADRs. Recognition of pattern of ADRs to antiretroviral drugs in a particular setup might sensitize the reporters to report ADRs, especially in setups dependent on spontaneous reporting. Aim and Objectives: The study of pattern and time-reaction sequence for ADRs reported to antiretroviral drugs. Materials and Methods: Retrospective study was conducted at a first-line antiretroviral therapy (ART) center after obtaining approval from the Institutional Ethics Committee. Pattern of ADRs associated with ART was done by analyzing the type of ADRs, severity, and outcome of ADRs reported to antiretroviral drugs. Mean duration of time lapse between administration of drug to onset of adverse drug reaction was calculated. Descriptive statistics was used for data analysis. Results: There were 73 adverse reactions reported. Most common type of adverse reaction was cutaneous (53.42%) followed by anemia (31%). Causality assessment of most ADRs was concluded as possible (60.27%). Most ADRs were of moderate severity and 12% were severe reactions. Reactions such as anemia and neuropsychiatric ADRs often occurred late, while maculopapular rash usually occurred within 30 days of drug administration. Conclusions: ADRs to ART include an array of reactions ranging from mild rash to psychosis or severe anemia. Most of these reactions are of moderate severity and have a favorable outcome. Many of these reactions actually occur almost a month after initiating a drug regime suggesting the need for intensive monitoring around this time.

Delayed Extensive Local Reaction to the mRNA-1273 Vaccine against SARS-CoV-2: A Case Report

In response to the COVID-19 pandemic, two mRNA vaccines (Comirnaty and Spikevax) received emergency use authorization from the European Medicines Agency. This case report aimed to report a delayed adverse reaction to the mRNA-1273 vaccine against COVID-19 from a Portuguese vaccination center. A case report was performed with medical observation and reported to the Portuguese Pharmacovigilance System, then investigated based on the WHO-UMC Causality Categories. A 66-year-old female patient with a clinical history of dyslipidemia, essential arterial hypertension, obesity, multinodular goitre and cholecystectomy, who presented delayed large cutaneous hypersensitivity reaction following Spikevax COVID-19 mRNA (mRNA-1273) vaccine administration. Our clinical findings (time and clinical appearance), along with evidence of previously reported histological findings, are strongly suggestive of T-cell-mediated hypersensitivity. There is no contraindication to the inoculation of subsequent doses in patients developing these clinical conditions, and vaccination should continue to be strongly encouraged.

Reações adversas medicamentosas em pacientes em quimioterapia e estratégias de intervenções / Adverse drug reactions in chemotherapy patients and intervention strategies / Reacciones adversas a medicamentos en pacientes quimioterápicos y estrategias de intervención

A quimioterapia do câncer pode ocasionar reações adversas medicamentosas (RAM), podendo resultar de interações medicamentosas (IM) e impactar na adesão. O presente estudo relatou as RAM apresentadas por pacientes em quimioterapia (QT) e propôs estratégias de intervenções. Este trabalho foi aprovado em comité de ética (5.160.503), sendo incluídos 23 pacientes em quimioterapia (oral- VO e/ou endovenosa- EV) e todos foram entrevistados. Recebiam apenas o QTEV, 20 pacientes e 2 QTEV e VO, a maioria em tratamento paliativo (50%), predomínio de estadiamento IV, sendo as doenças mais presentes de pâncreas (27,3%), estômago (22,7%) e mama (18,2%) e esquema mais usado foi Carboplatina + Paclitaxel. As principais comorbidades foram diabetes e hipertensão arterial. As interações medicamentosas foram classificadas em graves (45%), moderadas (55%) e intencional (75%), sendo necessário introdução de medicamentos de suporte (61%). Houve RAM de maior gravidade, neutropenia, sendo necessário a suspensão temporária, e de menor gravidade náuseas. Houve um óbito relacionado a evolução de doença e, talvez, o tratamento possa ter contribuído. Ao final, foram feitas as intervenções para cada caso e validado o formulário para a consulta farmacêutica a pacientes oncológicos.

Cancer chemotherapy can cause adverse drug reactions (ADRs), which can result from drug interactions (IM) and impact adherence. The present study reported the ADRs presented by patients undergoing chemotherapy (CT) and proposed intervention strategies. This work was approved by the ethics committee (5,160,503), and 23 patients on chemotherapy (oral-VO and/or intravenous-IV) were included and all were interviewed. Only received CTIV, 20 patients and 2 CTIV and VO, most in palliative treatment (50%), predominance of stage IV, being the most common diseases of pancreas (27.3%), stomach (22.7%) and breast (18.2%) and the most used regimen was Carboplatin + Paclitaxel. The main comorbidities were diabetes and arterial hypertension. Drug interactions were classified as severe (45%), moderate (55%) and intentional (75%), requiring the introduction of supportive drugs (61%). There were more severe ADRs, neutropenia, requiring temporary suspension, and less severe nausea. There was one death related to the evolution of the disease and, perhaps, the treatment may have contributed. At the end, interventions were made for each case and the form for the pharmaceutical consultation to cancer patients was validated.

La quimioterapia contra el cáncer puede causar reacciones adversas a los medicamentos (RAM), que pueden ser consecuencia de interacciones farmacológicas (IM) y repercutir en la adherencia. El presente estudio reportó las RAM presentadas por pacientes en quimioterapia (QT) y propuso estrategias de intervención. Este trabajo fue aprobado en comité de ética (5.160.503), se incluyeron 23 pacientes en quimioterapia (oral- VO y/o endovenosa-EV) y todos fueron entrevistados. Recibieron sólo QTEV, 20 pacientes y 2 QTEV y VO, la mayoría en tratamiento paliativo (50%), predominio de estadiaje IV, siendo las enfermedades más presentes las de páncreas (27,3%), estómago (22,7%) y mama (18,2%) y el esquema más utilizado fue Carboplatino + Paclitaxel. Las principales comorbilidades fueron la diabetes y la hipertensión arterial. Las interacciones farmacológicas se clasificaron como graves (45%), moderadas (55%) e intencionadas (75%), requiriendo la introducción de fármacos de apoyo (61%). La RAM más grave fue la neutropenia, que requirió la suspensión temporal, y la menos grave las náuseas. Hubo una muerte relacionada con la evolución de la enfermedad y, tal vez, el tratamiento pudo haber contribuido. Al final, se realizaron intervenciones para cada caso y se validó el formulario de consulta farmacéutica a pacientes oncológicos.

Literature case analysis of hyperammonemic encephalopathy caused by sodium valproate / 药物流行病学杂志

Objective To investigate the occurrence and clinical characteristics of the adverse reactions of hyperammonemic encephalopathy caused by sodium valproate and provide reference for the safe clinical use of the drug.Methods CNKI,WanFang Data,VIP,PubMed and Web of Science databases were electronically searched to collect case reports on valproate-induced hyperammonemic encephalopathy from the inception to March 2023.The extracted data was conducted for statistical analysis.Results A total of 37 documents with 41 patients were finally included.Among them,28 patients(68.3%)were males and 13 patients(31.7%)were females,aged 5 to 78 years,the median age was 41 years;most of the patients had no underlying diseases but the blood ammonia concentrations of them were abnormally high in laboratory tests,and the main clinical manifestations were neurological impairment such as cognitive impairment,drowsiness,coma and other disorders of consciousness.After drug discontinuation,drug switch and symptomatic treatment,they gradually recovered consciousness and the blood ammonia concentrations returned to normal.Conclusion It is not easy to recognize and detect the high blood ammonia encephalopathy caused by the application of sodium valproate in clinical practice,so the clinical performance and blood concentration of this drug should be closely monitored,and once the abnormalities are detected,patients should be treated symptomatically in time to ensure the safety of the drug use.

Case Reports of Adverse Drug Reactions Induced by Tislelizumab in A Hospital and the Literature Review / 医药导报

Objective To investigate the characteristics of adverse drug reactions(ADRs)induced by tislelizumab and to provide reference for clinic drug safety.Methods The ADR of tislelizumab in Beijing Friendship Hospital Affiliated to Capital Medical Univeristy from July 2021 to December 2022 were retrospectively analyzed.The case reports of ADR induced by tislelizumab from January 2019 to December 2022 in PubMed,ScienceDirect,Embase,Wanfang,VIP databases were searched.Age,sex,original diseases,adverse reaction time,clinical manifestation,treatment measures and clinical outcome were analyzed.Results A total of 30 patients including 8 cases in hospital and 22 cases in literature were collected.Among these patients,male accounted for 83.33%(25/30),and the highest proportion was from patients over 60 years old(21 patients,70.00%).Most ADRs occurred in 1-2 dose cycles of medication,mainly including skin toxicity in 8 patients,digestive disease in 6 patients and kidney injury in 4 patients.After the symptomatic treatment,29 patients improved and 1 patient died.Conclusion During the medication with tislelizumab,ADRs of skin,gastrointestinal tract and renal should be vigilant,and the changes of relevant indicators should be closely monitored.