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OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients. METHODS: Analytical, observational, case-control study of patients with ADE. For statistical analysis, the following were calculated: percentages, frequencies, averages; odds ratio, χ2 test and multiple binary logistic regression. Data analysis was carried out with the Statistical Package, for the Social Sciences 23 program. RESULTS: A 132 patients were registered: 66 cases (26 EM and 40 RAM) and 66 controls; with average age of 35 years (SD 17.41). The prevalence of adverse drug events was 3.6%. The most frequently reported medications: antibiotics and anti-inflammatories. The frequency of adverse events by gender was: 39.3% men and 60.7% women. The services with the greatest patient care: emergencies, surgery; the most frequent route of administration: intravenous (32.3%). The main symptoms: skin. (32.3%) frequent symptoms: cutaneous. Associated symptoms RAM: type A pruritus (OR: 8.5; p = 0.001; IC95%: 0.035-0.393), type B pruritus (OR: 11; p = 0.001; CI95%: 0.021-0.368) urticaria (OR: 19; p = 0.005; IC95%: 0.007-0.412). Risk factors Associated EAM: female (OR: 2.6; p = 0.05; CI95%: 1.33-5.43), history of allergy (OR: 3.4; p = 0.033; CI95%: 1.04-8.40), prolonged hospital stays (OR: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONS: Patient safety is a priority when prescribing any drug, which represents a key point in prevention.

OBJETIVO: Determinar la prevalencia, causas y factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados. MÉTODOS: Estudio de casos y controles, observacional, analítico, llevado a cabo en pacientes con eventos adversos a medicamentos. Para el análisis estadístico se calcularon: porcentajes, frecuencias, promedios; razón de momios, prueba de χ2 y regresión logística binaria múltiple. El análisis de los datos se efectuó con el programa Statistical Package, for the Social Sciencies 23. RESULTADOS: Se registraron 132 pacientes: 66 casos (26 EM y 40 RAM) y 66 controles, con edad promedio de 35 años (DS 17.41). La prevalencia de eventos adversos a medicamentos fue del 3.6%. Los medicamentos reportados con mayor frecuencia: antibióticos y antiinflamatorios. La frecuencia de eventos adversos por género fue: 39.3% hombres y 60.7% mujeres. Los servicios con mayor atención de pacientes: urgencias y cirugía; vía de administración más frecuente: intravenosa (32.3%). Los principales síntomas fueron los cutáneos. Los síntomas asociados con reacción adversa a medicamentos: prurito tipo A (RM: 8.5; p = 0.001; IC95%: 0.035-0.393), prurito tipo B (RM: 11; p = 0.001; IC95%: 0.021-0.368) urticaria (RM: 19; p = 0.005; IC95%: 0.007-0.412). Los factores de riesgo asociados con eventos adversos a medicamentos: mujer (RM: 2.6; p = 0.05; IC95%: 1.33-5.43), antecedente de alergia (RM: 3.4 p = 0.033; (IC95%: 1.04-8.40) y estancia hospitalaria prolongada (RM: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONES: La seguridad de los pacientes es una prioridad al momento de prescribir cualquier fármaco, lo que representa un punto clave en la prevención.

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OBJECTIVES: Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance. EVIDENCE ACQUISITION: A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270. RESULTS: Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I2 = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I2 = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I2 = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I2 = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention. CONCLUSION: EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.

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INTRODUCTION: Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option. CASE REPORT: We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient's hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes. DISCUSSION: PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.

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AIMS: Neonates hospitalized in neonatal intensive care units (NICUs) commonly experience adverse drug reactions (ADRs). Thus, we aimed to develop and validate a tool for predicting ADRs in neonates hospitalized in NICUs. METHODS: A nested case-control study in an open cohort with neonates admitted to the NICU of a maternity hospital in Natal, Brazil was conducted from January 2019 to January 2022 [Correction added on 4 December 2023, after first online publication: 2023 has been changed to 2019 in the preceding sentence.]. Neonates with ADR were randomly paired with 2 controls. For the development of the tool, a multivariate logistic regression was applied on 2/3 of the sample (cases with respective controls). The model's fit was evaluated using the Hosmer-Lemeshow test for calibration and the Brier score for performance assessment. Validation of the tool was performed by determining the area under the receiver operating characteristic curve with bootstrap adjusted c-statistics. RESULTS: In all, 450 neonates (150 cases and 300 controls) were included in the study. We identified 5 independent risk factors for ADR, 4 related to the neonate (current mechanical ventilation, heart rate ≥178 beats/min, intravenous medications, ≥5 prescription medications) and 1 to the mother (gestational hypertension). The tool had a classification cut-off point of ≥15, and its total score ranged from 0 to 34. In validation, the tool had an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI] 0.66-0.81) with sensitivity of 52.02% (95% CI 47.40-56.64) and specificity of 81.35% (95% CI 77.75-84.95). CONCLUSION: The tool demonstrated adequate discriminative ability and utilized 5 commonly monitored variables in the NICU.

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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.

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OBJECTIVES: To assess the efficacy and adverse events linked to the utilization of fentanyl for perioperative pain management in dentistry. METHODS: This systematic review of randomized clinical trials (RCTs) adhered to the PRISMA guidelines and incorporated various databases. RESULTS: Eleven RCTs studying 674 patients were analyzed. Perioperative pain was predominantly evaluated in patients undergoing surgery for impacted molars, although some studies also included patients with other conditions such as oral submucous fibrosis, maxillary cancer, bony temporomandibular joint ankylosis, irreversible pulpitis, among others. Combined with dexmedetomidine, fentanyl produced enhanced analgesic effects. It demonstrated comparable efficacy when compared to nefopam and nalbuphine. Both intranasal and intravenous administration routes proved equally effective. In four RCTs, the transdermal fentanyl patch outperformed the control group, except in the clinical trial where it was compared to ropivacaine. The main adverse events associated with the use of fentanyl included nausea, vomiting, drowsiness, delirium, and respiratory depression; however, they were like those reported in the comparison groups. CONCLUSIONS: While fentanyl demonstrated satisfactory perioperative analgesic efficacy, there were other alternatives that displayed better or comparable outcomes. Due to the risks and potential for misuse of fentanyl, these alternatives must be considered although adverse events were also reported.

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INTRODUCTION: Adverse drug reactions (ADRs) to antiseizure therapy can worsen the quality of life, reduce adherence, and potentially lead to treatment discontinuation and uncontrolled seizures. OBJECTIVES: The aim of the study was to develop a prognostic model for ADRs to antiseizure therapy in adult patients with epilepsy from Colombia. METHODS: This case-control study included adult patients with epilepsy, who were separated into two groups: one group with ADRs to antiseizure therapy (cases), as determined by a complete evaluation conducted by an epileptologist, and another group without ADRs (controls). Variables were analyzed to identify statistical differences between the two groups and were then selected to construct a prognostic model using logistic regression. The Bonferroni method was applied for multiple comparisons. RESULTS: Three hundred fifty-four patients with epilepsy were studied. One hundred and fifty (42%) patients had ADRs and 204 (57%) patients did not have ADs. A total of 362 ADRs were reported, with a third of them being general symptoms and most frequently occurring with older-generation antiseizure drugs (58%). Female sex, drug-resistant epilepsy, LEV, and CZP were risk factors, whereras the presence of tumoral etiology, absence of seizure triggers, and VPA were identified as protective factors. A prognostic model was constructed using previously reported risk factors for ADRs to antiseizure therapy and other variables available in this population study. In the multivariable analysis, the number of previously used antiseizure drugs (1, 2, or ≥3), TPM, CZP, LEV, PHT, and female sex were predictors of ADRs. The corrected p-values were estimated by the Bonferroni method; however, not all the variables achieved statistical significance with this adjustment. CONCLUSIONS: In adult patients with epilepsy from Colombia, we found that the number of previously used antiseizure drugs, TPM, CZP, LEV, PHT, and female sex were predictive factors for ADRs to antiseizure therapy.

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OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients of a General Hospital. METHODS: Observational and analytical case-control study, carried out in patients hospitalized for adverse drug events, treated at the Hospital General Dr. Eduardo Vázquez N, in Puebla, Mexico, between, June 2019 to June 2021. For the statistical analysis, percentages, frequencies, means, odds ratio, χ2, and multiple binary logistic regression were used. Data were analyzed using the Statistical Package for the Social Sciences 23 program. RESULTS: A total of 132 patients (66 cases and 66 controls) were registered. Of the group of cases, 26 patients treated for medication error and 40 with adverse drug reaction were reported. The prevalence of adverse drug events was 3.6%. The drugs and factors associated with the most reported adverse events were: antibiotics, anti-inflammatories; average age of 35 years (SD: 17.41); gender: 39.3% men, 60.7% women; services re-ported with the greatest attention: Emergencies and Surgery; frequent route of administration: intravenous (32.3%); main symptoms: skin; symptoms associated with adverse drug reactions: type A pruritus [OR: 8.5, p = 0.001(CI95%: 0.035-0.393)], type B pruritus [OR: 11, p = 0.001 (CI95%: 0.021-0.368)]; urticaria [OR: 19, p = 0.005(CI95%: 0.007-0.412)]. Risk factors associated with adverse events were: female gender [OR: 2.6, p = 0.05 (CI95%: 1.33-5.43)], history of allergy [OR: 3.4, p = 0.033 (CI95%: 1.04-8.40)] and prolonged hospital stay [OR: 5.4, p = 0.023 (CI95%: 3.82-6.74)]. CONCLUSIONS: The majority of ADEs were EM or ADR type A, both preventable reactions, so patient safety should be a priority when prescribing.

OBJECTIVO: Determinar la prevalencia, causas y factores de riesgo en pacientes hospitalizados por eventos ad-versos a medicamentos. MÉTODOS: Estudio de casos y controles, observacional y analítico, llevado a cabo en pacientes hospitalizados por eventos adversos a medicamentos, atendidos en el Hospital General Dr. Eduardo Vázquez N, Puebla, México, entre junio de 2019 y junio de 2021. Para el análisis estadístico se utilizaron porcentajes, frecuencias, promedios, razón de momios, χ2 y regresión logística binaria múltiple. Los datos se analizaron con el programa Statistical Package, for the Social Sciencies 23. RESULTADOS: Se registraron 132 pacientes (66 casos y 66 controles). Del grupo de casos se informaron 26 pacientes atendidos por error de medicación y 40 con reacción adversa a medicamentos. La prevalencia de eventos adversos a medicamentos fue del 3.6%. Los medicamentos y factores asociados con eventos adversos más reportados fueron: antibióticos, antiinflamatorios; edad promedio de 35años (DE: 17.41); sexo: 39.3% hombres, 60.7% mujeres; servicios reportados con mayor atención: Urgencias y Cirugía; vía administración frecuente: intravenosa (32.3%); síntomas principales: cutáneos; síntomas asociados con reacciones adversas a medicamentos: tipo A prurito [RM: 8.5, p = 0.001(IC95%: 0.035-0.393)], tipo B prurito [RM:11, p = 0.001 (IC95%: 0.021-0.368)]; urticaria [RM: 19, p = 0.005(IC95%: 0.007-0.412)]. Los factores riesgo asociados con eventos adversos fueron: género femenino [RM: 2.6, p = 0.05 (IC95%: 1.33-5.43)], antecedente de alergia [RM: 3.4, p = 0.033 (IC95%: 1.04-8.40)] y estancia intrahospitalaria prolongada [RM: 5.4, p = 0.023 (IC95%: 3.82-6.74)]. CONCLUSIONES: La mayor parte de los eventos adversos a medicamentos se originan por errores de medicación o reacciones adversas a fármacos tipo A; sin embargo, ambos pueden prevenirse. La seguridad del paciente debe ser prioridad al momento de prescribir cualquier tipo de medicamento.

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Purpose of overview: The constant surge in accessing essential medicines creates a greater need for continuous monitoring of usage. The inability to source active pharmaceutical ingredients during the COVID-19 pandemic resulted in drug shortages that increased online requests for medications. E-commerce and social sites have opened the floodgate for the marketing of falsified, substandard, and unregistered pharmaceuticals, making them easily accessible to consumers with the click of a button. A high prevalence of such products with compromised quality highlights further the need for enhanced post-marketing vigilance of safety and quality within the pharmaceutical industry. This review aims to assess the extent to which pharmacovigilance (PV) systems in selected Caribbean countries conform to the minimum World Health Organization (WHO) requirements, highlight the importance of PV in ensuring the safer use of medicines across the Caribbean region, and identify opportunities and challenges in building comprehensive PV systems. Recent Findings: The review finds that while major advancements in PV and adverse drug reaction (ADR) monitoring have occurred in Europe and other parts of the Americas, little has been done in the Caribbean region. Only a few countries in the region are active members of the WHO's global PV network, and ADR reporting is minimal. The reason for low reporting includes a lack of awareness, commitment, and participation of healthcare professionals, manufacturers, authorized distributors, and the general consumers. Summary: Nearly all established national PV systems do not fully conform to the minimum PV requirements by the WHO. Legislation, regulatory framework, political commitment, adequate funding, strategies, and incentives to encourage reporting of ADRs are needed to build sustainable PV systems in the Caribbean.

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PURPOSE: To investigate the association between the use of antidepressants and the risk of upper gastrointestinal tract bleeding (UGIB). METHODS: A Case-control study was conducted in a Brazilian hospital complex. Cases were defined as patients with a diagnosis of UGIB and controls as patients admitted for reasons unrelated to gastrointestinal bleeding, gastric concerns, or complications associated with low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs) use. Sociodemographic and clinical data, comorbidities, drug therapy in use (long-term use and self-medication), and lifestyle habits were recorded through face-to-face interviews. Two groups were defined: use of antidepressants in general and use of antidepressants according to their affinity for serotonin transporters. The presence of synergism between the concomitant use of antidepressants and LDA or NSAIDs on the risk of UGIB was also explored. FINDINGS: A total of 906 participants were recruited (200 in the case group and 706 in the control group). The use of antidepressants was not associated with the risk of UGIB (odds ratio [OR] = 1.503; 95% CI, 0.78-2.88) or the use of antidepressants with high affinity for serotonin receptors (OR = 1.983; 95% CI, 0.81-4.85). An increased risk of UGIB was observed in concomitant users of antidepressants and LDA (OR = 5.489; 95% CI, 1.60-18.81) or NSAIDs (OR = 18.286; 95% CI, 3.18-105.29). Despite the lack of significance, the use of antidepressants appears to be a positive modifier of UGIB risk in LDA and NSAID users. IMPLICATIONS: These findings indicate an increased risk of UGIB in concomitant users of antidepressants and LDA or NSAIDs, suggesting the need to monitor antidepressant users, especially those most likely to develop UGIB. In addition, further studies with larger sample sizes are needed to confirm these findings.

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Self-medication is a part of the self-care practices carried out by the elderly in their environment. The aim of this case report is to show how the self-medication of fluoxetine and dimenhydrinate in an older adult can induce serotoninergic and cholinergic syndromes, showing symptoms such as nausea, tachycardia, tremor, loss of appetite, memory loss, decreased vision, falls, and increased urination. An older adult who has been diagnosed with arterial hypertension, dyslipidemia, diabetes mellitus, and a recent diagnosis of essential thrombosis is the subject of this case report. After the analysis of the case, cessation of fluoxetine was recommended to avoid withdrawal symptoms, therefore decreasing the need for dimenhydrinate and the medicines used for dyspepsia. After the recommendation, the patient showed an improvement in the symptoms. Finally, the comprehensive evaluation process of the medication in the Medicines Optimization Unit achieved the detection of the problem and improved the patient's health condition.

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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)

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BACKGROUND: Adverse drug reactions (ADRs) are of great concern in clinical practice. Pharmacogenetics can identify individuals and groups at increased risk of developing ADRs, enabling treatment adjustments to improve outcomes. The study aimed to determine the prevalence of ADRs related to drugs with pharmacogenetic evidence level 1A in a public hospital in Southern Brazil. RESEARCH DESIGN AND METHODS: ADR information was collected from the pharmaceutical registries from 2017 to 2019. Drugs that have pharmacogenetic evidence level 1A were selected. Public genomic databases were used to estimate the genotypes/phenotypes frequency. RESULTS: During the period, 585 ADRs were spontaneously notified. Most were moderate (76.3%), whereas severe reactions accounted for 33.8%. Additionally, 109 ADRs caused by 41 drugs presented pharmacogenetic evidence level 1A, representing 18.6% of all notified reactions. Depending on the drug-gene pair, up to 35% of individuals from Southern Brazil could be at risk of developing ADRs. CONCLUSIONS: Relevant amount of ADRs were related to drugs with pharmacogenetic recommendations on drug labels and/or guidelines. Genetic information could guide and improve clinical outcomes, decreasing ADR incidence and reducing treatment costs.

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INTRODUCTION: Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. OBJECTIVE: To assess ADRs associated with anti-infective use in Brazilian hospitalized children. METHODS: A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0-11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. RESULTS: A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001). CONCLUSION: Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.

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A quantitative descriptive study based on Brazilian Active Pharmacovigilance of Dolutegravir (DTG) Project was performed to describe the adverse drug reactions (ADRs) to DTG reported and to evaluate the noncompleteness of data from DTG active pharmacovigilance in Brazil. ADRs and clinical and individual data were obtained from information from the Pharmacovigilance Questionnaire from April 2017 to August 2019. The reported ADRs were classified using the Medical Dictionary for Regulatory Activities (MedDRA). In the evaluated period, 249,066 individuals using DTG participated in the active pharmacovigilance of DTG, with 3472 (1.39%) reporting ADRs at least once. A total of 6312 ADRs were reported, of which 57.56% were persistent and 81.46% were not serious according to the individuals' reports. Most of the reported ADRs were gastrointestinal, neurological and psychiatric. ADRs related to neural tube defects and serious neuropsychiatric ADRs have been reported. Completion of more than half of the fields in the Pharmacovigilance Questionnaire was excellent. The frequency of ADR was low in relation to the number of people living with HIV (PLHIV) using DTG in Brazil, which suggests good tolerability and safety of DTG. The DTG active pharmacovigilance database in Brazil showed good data completeness.

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A evolução da biotecnologia somada à ascensão da tecnologia para recombinação do DNA impulsionou a produção de biológicos ao longo de décadas. Com o término das patentes, os biossimilares emergiram com potencial de gerar um grande impacto na acessibilidade e assim estabelecer seu lugar no mercado após comprovação da equivalência com o medicamento biológico. Entretanto, as preocupações sobre as trocas de medicamentos biológicos e biossimilares é um importante debate atual que ressalta a relevância de acompanhamento pós mercado das pessoas em uso de biofármacos. Este estudo teve como objetivo elaborar um protótipo para identificar e validar os dados necessários para a construção de um software específico para o monitoramento dos medicamentos biossimilares para doenças inflamatórias imunomediadas, tendo em vista o processo de trabalho dos profissionais de saúde e da indústria farmacêutica, considerando os aspectos legais e legislativos das agências reguladoras em benefício do doente crônico. Trata-se de uma pesquisa aplicada, com abordagem qualitativa, na modalidade pesquisa-ação. A população amostral foi constituída por profissionais de saúde, profissionais da indústria farmacêutica, agência reguladora, usuários de medicamento biológico e medicamento biossimilar e especialistas de informática que aceitaram participar da pesquisa por meio da assinatura do Termo de Consentimento Livre e Esclarecido. Abordados na primeira etapa do estudo, os apontamentos dos integrantes do Comitê de Especialistas agregaram as diretrizes estabelecidas pelas agências reguladoras e contribuíram com o levantamento de requisitos que, permeado por padrões de terminologia, direcionou o desenvolvimento dos protótipos (estático e de software). O Adobe Illustrator® foi o editor de imagens vetoriais utilizado para desenvolver o protótipo estático e contribuir para consolidar as telas, ao passo que o protótipo de software explorou as potencialidades da tecnologia Angular e favoreceu a interação do usuário com as telas desenvolvidas. Na segunda fase do estudo, os integrantes do Comitê de Avaliadores acessaram o protótipo para avaliação da tecnologia por meio da aplicação de um questionário. Os resultados evidenciam a importância de desenvolver estratégias para identificar os desvios de qualidade e dessa forma minimizar os eventuais danos das novas gerações de medicamentos. Soma-se a relevância de identificar as trocas de medicamentos biológicos e biossimilares e qualificar as informações para favorecer o acompanhamento pós mercado dos biofármacos e, assim, fortalecer a farmacovigilância e contribuir com a segurança do paciente. A aproximação entre o pesquisador e as pessoas implicadas na jornada do paciente em uso de medicamento biológico e biossimilar proporcionou a inserção de perspectivas não previstas pela literatura e, sobretudo, delineou potenciais soluções para os problemas apontados.

The evolution of biotechnology added to the rise of technology for DNA recombination boosted the production of biologicals for decades. With the end of patents, biosimilars emerged with the potential to generate a great impact on accessibility and thus establish their place in the market after proof of equivalence with biological medicine. However, concerns regarding the exchange of biological and biosimilar medicines is an important current debate that highlights the relevance of post-market monitoring of people using biopharmaceuticals. This study aimed to develop a prototype to validate the data necessary for the monitoring of biological and biosimilar medicines for immune-mediated inflammatory diseases. It is an applied research, with a qualitative approach, in the action-research modality. The sample population consisted of health professionals, professionals from the pharmaceutical industry, regulatory agency, users of biological and biosimilar products and IT specialists who agreed to participate in the research by signing the Free and Informed Consent Form. Approached in the first stage of the study, the notes of the members of the Committee of Experts added the guidelines established by the regulatory agencies and contributed to the survey of requirements that, permeated by terminology standards, guided the development of prototypes (static and software). Adobe Illustrator® was the vector image editor used to develop the static prototype and contributed to consolidate the developed screens, while the software prototype explored the potential of Angular technology and favored user interaction with the screens developed. In the second phase of the study, the members of the Committee of Evaluators accessed the prototype for evaluating the technology through the application of a questionnaire. The results show the importance of developing strategies to identify quality deviations and minimize the potential damages of new generations of medicines. biopharmaceuticals and, thus, strengthen pharmacovigilance and contribute to patient safety. The approximation between the researcher and the people involved in the journey of the patient using biological and biosimilar medicines provided the insertion of perspectives not foreseen in the literature and, above all, outlining potential solutions to the problems mentioned.

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(1) Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tears) for characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting. (2) Methods: The underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tears). The factors related to the report in spontaneous reporting through statistical tests were also determined. (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tears. Additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females when compared with spontaneous reporting and active surveillance. (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Additionally, since underreporting seems to b selective, the role of certain aspects, such as gender, seriousness, severity, and unexpected ADRs, must be considered in future research.

RESUMO

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines' selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance.

RESUMO

Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.

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Introdução: Danos decorrentes de eventos adversos relacionados a medicamentos (EAM) estão entre os mais frequentes no mundo. Logo, seu monitoramento é essencial, especialmente entre os idosos que apresentam maior risco de sofrer tais danos. Adicionalmente, a pandemia da COVID-19, a sua elevada incidência entre idosos e o uso frequente de medicamentos off-label reforçaram a importância do monitoramento de EAM nessa população. Objetivo: Descrever as suspeitas de EAM entre idosos no Brasil antes e após o início da pandemia por COVID-19. Método: Foi realizada a descrição das suspeitas de EAM notificadas no sistema VigiMed da Agência Nacional de Vigilância Sanitária envolvendo idosos (idade ≥ 65 anos) no período pré-pandemia (01/2019 a 03/2020) e pós-início da pandemia (04/2020 a 06/2021). A diferença entre a proporção de EAM graves entre os períodos foi avaliada mediante teste qui-quadrado de Pearson. Resultados: Foram notificadas 57.167 suspeitas de EAM no período global avaliado; 22,2% envolviam idosos. No período pré-pandemia, 2.924 suspeitas de EAM foram notificadas (44,2% eram EAM graves), destacando-se aquelas envolvendo antineoplásicos, antimicrobianos e anticoagulantes. No período pós-início da pandemia, 9.771 suspeitas de EAM foram notificadas (57,5% graves), destacando-se a hidroxicloroquina e as vacinas contra a COVID-19. A diferença na proporção de suspeitas de EAM graves notificadas para idosos entre os períodos avaliados foi estatisticamente significativa (p < 0,001). Conclusões: Notificações de EAM e estudos que avaliem EAM entre idosos são essenciais para gerar informações que possam subsidiar a otimização da farmacoterapia e a priorização de redução de danos entre eles, sobretudo no contexto pandêmico que afeta consideravelmente essa população.

Introduction: Harm resulting from adverse drug events (ADE) is among the most frequent in the world. Therefore, its monitoring is essential, especially among older adults, who are at greater risk of suffering such type of harm. Additionally, the COVID-19 pandemic, its high incidence among older adults and frequent use of off-label medications have reinforced the importance of monitoring ADE in this population. Objective: To describe the suspected ADE among older adults in Brazil before and after the beginning of the COVID-19 pandemic. Method: A description of suspected ADEs reported in the VigiMed system of the National Health Surveillance Agency was carried out, involving older adults (age ≥ 65 years) in the pre- (01/2019 to 03/2020) and post-onset of the pandemic period (04/2020 to 06/2021). The difference between the proportion of severe ADE between the periods was evaluated using Pearson's chi-square test. Results: 57,167 suspected ADE were reported in the global period evaluated; 22.2% involved older adults. In the pre-pandemic period, 2,924 suspected ADEs were reported (44.2% were severe ADEs), especially those involving antineoplastic, antimicrobial, and anticoagulant drugs. In the post-pandemic period, 9,771 suspected ADEs were reported (57.5% severe), especially related to hydroxychloroquine and vaccines against COVID-19. The difference in the proportion of severe suspected ADE reported for the older adults between the periods evaluated was statistically significant (p < 0.001). Conclusions: ADE notifications and studies that evaluate ADE among older adults are essential to generate information that can support drug therapy optimization and prioritization of harm reduction among them, especially in the pandemic context that considerably affects this population.