Characterization of adverse events to hydroxychloroquine, ivermectin, azithromycin and tocilizumab in patients hospitalized due to COVID-19 in a Peruvian Social Health Insurance hospital. / Caracterización de los eventos adversos a hidroxicloroquina, ivermectina, azitromicina y tocilizumab en pacientes hospitalizados por la COVID-19 en un hospital del Seguro Social de Salud del Perú.

OBJECTIVE.: To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. MATERIALS AND METHODS.: We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. RESULTS.: We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. CONCLUSIONS.: We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.

OBJETIVOS.: Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta¼ en el tratamiento de pacientes hospitalizados por la COVID-19. MATERIALES Y MÉTODOS.: Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. RESULTADOS.: Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. CONCLUSIONES.: Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.

Caracterización de eventos adversos a hidroxicloroquina, ivermectina, azitromicina y tocilizumab en pacientes hospitalizados por COVID-19 en un hospital del Seguro Social de Salud del Perú / Characterization of adverse events to hydroxychloroquine, ivermectin, azithromycin and tocilizumab in patients hospitalized due to COVID-19 in a Peruvian Social Health Insurance hospital

Objetivos. Caracterizar los eventos adversos (EA) asociados a hidroxicloroquina (HQ), azitromicina (AZI), tocilizumab (TOB) e ivermectina (IVM) prescritos como «fuera de etiqueta» en el tratamiento de pacientes hospitalizados por la COVID-19. Materiales y métodos. Se realizó un análisis secundario transversal de la base de datos del sistema de farmacovigilancia del Seguro Social de Salud del Perú (EsSalud) de las notificaciones de EA a HQ, AZI, TOB e IVM provenientes del Hospital Nacional Edgardo Rebagliati Martins de abril a octubre del 2020. Se revisaron las historias clínicas digitales, se estimaron las tasas de reporte de EA y se evaluaron sus características por tipo de fármaco, tiempo de aparición, tipo por órgano-sistema afectado, gravedad y causalidad. Resultados. Se identificaron 154 notificaciones que describen un total de 183 EA posiblemente relacionados con HQ, AZI, TOB e IVM, siendo 8% la tasa de reporte de EA. La mediana de tiempo de aparición de EA fue de 3 días (RIC: 2-5). La mayoría fueron cardiovasculares, destacándose la prolongación del intervalo QT. Se observaron EA hepatobiliares principalmente asociados a TOB. La mayoría de los casos fueron moderados, no obstante, el 10,4% fue grave. Conclusiones. Se identificaron EA potencialmente asociados al uso de HQ, AZI, TOB e IVM contra la COVID-19, siendo los más frecuentes los de tipo cardiovasculares. A pesar de que la AZI, HQ e IVM poseen perfiles conocidos de seguridad, su empleo en la COVID-19 podría incrementar la aparición de EA por los factores de riesgo propios de esta infección. Se sugiere reforzar la vigilancia, especialmente, de TOB.

Objective. To characterize the adverse events (AEs) related to the off-label use of hydroxychloroquine (HQ), azithromycin (AZI), tocilizumab (TOB) and ivermectin (IVM) for the treatment of COVID-19 in hospitalized patients. Materials and Methods. We conducted a secondary cross-sectional analysis of the Peruvian Social Health Insurance (EsSalud) pharmacovigilance system database of AE notifications to HQ, AZI, TOB and IVM in the Edgardo Rebagliati Martins National Hospital from April to October 2020. Information was collected from digital medical records. We estimated AE reporting rates and evaluated their characteristics by drug type, time of occurrence, type by the affected organ-system, severity and causality. Results. We identified 154 notifications describing a total of 183 AE possibly related to HQ, AZI, TOB and IVM; the reporting rate was 8%. The median time of AE occurrence was 3 days (IQR: 2-5). Most were cardiovascular events; prolongation of the QT interval was the most frequent. Hepatobiliary AEs were mainly associated with TOB. Most cases were moderate, however, 10.4% were severe. Conclusions. We found AEs potentially associated with the use of HQ, AZI, TOB and IVM against COVID-19; cardiovascular events were the most frequent. Although AZI, HQ and IVM have known safety profiles, their use against COVID-19 could increase the occurrence of AE due to the risk factors inherent to this infection. Surveillance systems must be improved, especially those for TOB.

A 3-Year-Old Girl with Recurrent Infections and Autoimmunity due to a STAT1 Gain-of-Function Mutation: The Expanding Clinical Presentation of Primary Immunodeficiencies.

We report a 3-year-old Peruvian girl, born to non-consanguineous parents. At the age of 8 months, she had a severe pneumonia complicated with empyema that required thoracic drainage and mechanical ventilation. Although no microorganisms were isolated, the patient recovered with broad-spectrum antibiotics. Since that date, she has presented multiple episodes of pneumonia and recurrent episodes of bronchospasm. At 1 year 5 months of age, the patient began with recurrent episodes of oropharyngeal, vaginal, and skin candidiasis, which improved transiently after using oral azole drugs. At 2.5 years of age, she was admitted with lupus-like syndrome, including serositis, hemolytic anemia, thrombocytopenia, and positive antinuclear (1:80) and dsDNA (1:10) autoantibodies. Available immunologic testing was not contributory. Imaging studies revealed bilateral ethmoidal sinusitis and mild hepatomegaly. Bone marrow analysis did not showed evidence of leukemia or myelodysplasia, while renal biopsy concluded mild mesangial proliferation. Genetic studies revealed a pathogenic heterozygous signal transducer and activator of transcription 1 gain-of-function mutation (WT/P293L). The clinical status and lung function of the patient has worsened progressively. She has not achieved an optimal response to therapy, including high-dose intravenous immunoglobulin, GM-CSF, prophylactic antibiotics and antifungal drugs, so we plan to perform hematopoietic stem cell transplantation.