Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency / Vendas de "kit-COVID" e reações adversas a esses medicamentos relatadas pela Agência Nacional de Vigilância Sanitária / Ventas de medicamentos del "kit-COVID" y reacciones adversas a los medicamentos notificadas por la Agencia Nacional de Vigilancia Sanitaria

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.

Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.

The impact of hydroxychloroquine and azithromycin on the corrected qt interval in patients with the novel Coronavirus disease 2019

SUMMARY OBJECTIVE: With the coronavirus disease 2019 (COVID-19) continuing to spread all over the world, although there is no specific treatment until now, hydroxychloroquine and azithromycin have been reported to be effective in recent studies. Although long-term use of hydroxychloroquine and azithromycin has been reported to cause QT prolongation and malign arrhythmia, there is not enough data about the effect of short-term use on arrhythmia. Therefore, this study aims to assess the effect of hydroxychloroquine alone and hydroxychloroquine + azithromycin on corrected QT (QTc). METHODS: A baseline electrocardiogram and on-treatment baseline electrocardiogram were retrospectively collected in COVID-19 patients who received hydroxychloroquine and/or azithromycin. The QTc interval was calculated, and the baseline and peak QTc intervals were compared. In addition, the peak QTc intervals of monotherapy and combination therapy were compared. RESULTS: Of the 155 patients included, 102 (65.8%) patients were using hydroxychloroquine, and 53 (34.2%) patients were using hydroxychloroquine + azithromycin combination. The use of both hydroxychloroquine alone and hydroxychloroquine + azithromycin combined therapy significantly prolonged the QTc, and the QTc interval was significantly longer in patients receiving combination therapy. QTc prolongation caused early termination in both groups, 5 (4.9%) patients in the monotherapy group and 6 (11.3%) patients in the combination therapy group. CONCLUSION: In this study, patients who received hydroxychloroquine for the treatment of COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc.

Effects of Chloroquine and Hydroxychloroquine on the Cardiovascular System - Limitations for Use in the Treatment of COVID-19

Abstract Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial drugs, with anti-inflammatory properties that justify their use in the treatment of systemic lupus erythematosus and rheumatic diseases. A pandemic caused by the new coronavirus led the entire world's scientific community to look for drugs already available on the market, capable of exercising beneficial actions in the fight against the disease. Preliminary studies in patients, as well as in vitro studies, suggested possible therapeutic effects associated with the use of HCQ and CQ in the treatment of COVID-19. Despite controversies over the effects of these drugs in combating the "cytokine storm" associated with COVID and the dismal of results in different clinical trials in Brazil, their use has been encouraged and several ongoing investigative studies are underway. In addition to the possible beneficial effects on the prognosis of patients with SARS-CoV-2, such drugs include varied effects on the cardiovascular system, ranging from positive developments related to their vasodilator properties to potential negative effects, such as cardiotoxicity. This work presents the main effects exerted by these drugs on the cardiovascular system, in order to contribute to a scientific discussion about the repurposing of these drugs in the context of COVID-19.

Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19

ABSTRACT Objectives: To assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. Method: Retrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes. Results: The active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47-70) in the active group and 65 (47−77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. Conclusions: Patients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

Efetividade e toxicidade da cloroquina e da hidroxicloroquina associada (ou não) à azitromicina para tratamento da COVID-19. O que sabemos até o momento? / Effectiveness and toxicity of chloroquine and hydroxychloroquine associated (or not) with azithromycin for the treatment of COVID-19. What do we know so far?

Objetivos: identificar as evidências científicas existentes até o presente momento sobre a efetividade do uso da cloroquina, da hidroxicloroquina associada (ou não) à azitromicina para tratamento da afecção pelo coronavírus e seus possíveis efeitos adversos e tóxicos aos seres humanos. Métodos: a revisão narrativa utilizou-se das bases de dados PubMed, LILACS, SciElo e Google Acadêmico. Nessas, buscaram-se estudos, utilizando-se dos descritores "covid", "coronavirus", "SARS-CoV-2", "chloroquine", "hydroxychloroquine", "azithromycin" e "adverse effects" junto com os operadores booleanos "AND" e "OR". Resultados: sete artigos, das trinta publicações encontradas, atenderam aos critérios de inclusão, sendo utilizados para compor a presente revisão. Dos sete ensaios clínicos analisados, cinco apresentaram resultados de cura e/ou remissão dos sintomas e/ou redução da carga viral dos pacientes, no entanto apresentaram muitas limitações. Conclusão: a literatura científica é escassa e divergente quanto à efetividade dos medicamentos cloroquina e hidroxicloroquina associada (ou não) à azitromicina no tratamento da COVID-19, pela rápida disseminação e instalação da pandemia na esfera global. É necessário a realização de ensaios clínicos pragmáticos, envolvendo um número maior de pacientes, para que seja possível analisar a efetividade no combate ao coronavírus, bem como a segurança do uso desses fármacos.(AU)

Objective: to identify the scientific evidence existing to date on the effectiveness of the use of chloroquine, hydroxychloroquine associated (or not) to azithromycin for the treatment of COVID-19 disease and its possible adverse drug events and toxicity to human health. Methods: the narrative review was performed using the PubMed, LILACS, SciElo and Google Academic databases. In these, studies were sought, using the descriptors "covid", "coronavirus", "SARS-CoV-2", "chloroquine", "hydroxychloroquine", "azithromycin", "adverse effects" and "toxicity", together with the Boolean operator "AND" and "OR". Results: seven studies of thirty publications met the inclusion criteria and were used in the present review. Of the seven clinical trials analyzed, five showed results of cure and/or remission of symptoms and/or reduction of patients' viral load, however these studies had many limitations. Conclusion: scientific literature is scarce and divergent as to the effectiveness of the drugs chloroquine and hydroxychloroquine associated (or not) with azithromycin in the treatment of COVID-19, due to the rapid spread and installation of the pandemic in the global sphere. It is necessary to carry out pragmatic clinical trials, involving a larger number of patients, so that it is possible to analyze the effectiveness in combating the coronavirus, as well as the safety of the use of these drugs.(AU)

Potenciales efectos pro-arrítmicos de la farmacoterapia contra SARS-CoV-2 / Potential pro-arrhythmic effects of pharmacotherapy against SARS-CoV-2

Resumen La pandemia por el virus SARS-COV-2 causante de la enfermedad COVID-19 representa un reto mundial dada su alta tasa de transmisión y ausencia de una terapia efectiva o vacuna. Este escenario ha propiciado el uso de diversos fármacos que in vitro han demostrado un potencial efecto contra el virus. Sin embargo, el tiempo no ha sido suficiente para evaluar su efectividad clínica con el adecuado rigor científico que precede a la prescripción de medicamentos. El uso de cloroquina/hidroxicloroquina, azitromicina y esquemas antivirales ha sido propuesto por diversos grupos, apoyado por series de pacientes limitada en número. Si bien puede representar la única esperanza para muchos enfermos, es importante conocer los principales efectos adversos asociados al uso de estas drogas y seleccionar mejor a los pacientes que puedan beneficiarse de ellas. El riesgo de arritmias ventriculares incrementa tanto por el uso de fármacos como por la gravedad de la propia enfermedad viral.

Abstract The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.

Implicaciones cardiovasculares de la infección por SARS-CoV-2: revisión de literatura / Cardiovascular implications of SARS-CoV-2 infection: a literature review

En diciembre de 2019 se reportó en Wuhan, China, la aparición de una nueva cepa de coronavirus SARS-CoV-2 que producía un compromiso pulmonar severo y progresaba a estrés respiratorio agudo. A la fecha, son más de diecisiete millones los casos confirmados y más de medio millón los fallecidos en todo el mundo a causa de COVID-19. Los estudios reportan que los pacientes con enfermedad cardiovascular son más susceptibles a contraer esta enfermedad y a presentar más complicaciones. El propósito de esta revisión es proporcionar información actualizada para los profesionales de la salud que atienden a pacientes con COVID-19 y que tienen además enfermedad cardiovascular y por ende un riesgo elevado de complicaciones y mortalidad. Realizamos una búsqueda de bibliografía científica acerca de la asociación de enfermedad cardiovascular y COVID-19 en diferentes bases de datos como Scopus, MEDLINE vía PubMed y Cochrane Library. El tratamiento con inhibidores de la enzima convertidora de angiotensina y bloqueadores del receptor de angiotensina ha sido motivo de discusión y no hay evidencia sólida para contraindicarlo en pacientes con COVID-19. Respecto al tratamiento con hidroxicloroquina asociado o no con azitromicina, hay evidencia que demuestra un mayor riesgo con su utilización, que beneficio clínico y/o disminución de mortalidad. En este contexto, los pacientes con insuficiencia cardíaca representan un grupo importante de riesgo por su condición per se y por el dilema diagnóstico generado al evaluar un paciente con COVID-19, en el que los signos de insuficiencia cardíaca aguda podrían enmascararse. Por otro lado, en los pacientes con síndrome coronario agudo, el enfoque terapéutico inicial podría cambiar en el contexto de la pandemia, aunque sólo sobre la base de opiniones de expertos. Quedan, sin embargo, muchos temas en controversia que serán motivo de investigaciones futuras.

In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.

Neutropenia grave secundaria al tratamiento médico de una adenitis por micobacterias no tuberculosas / Severe neutropenia as side effect of medical treatment in nontuberculous mycobacterial adenitis

Non-tuberculous mycobacterial adenitis is getting more common in our environment. Epidemiologic studies and clinical trials published nowadays are limited. We present a 2-years-old boy diagnosed of Mycobacterium intracellulare adenitis and severe neutropenia as side effect of combined treatment with oral azythromycin and rifabutin, which recovers after suspending the second one. Liver metabolism of macrolide seems to increase other drugs toxicity, in this case, rifabutin. The patient eventually needed surgery due to persistence of the adenitis despite treatment with antibiotics.

Las adenopatías por micobacterias no tuberculosas (AMNT) son cada vez más frecuentes en nuestro medio. Los estudios epidemiológicos y ensayos clínicos controlados publicados hasta la fecha son escasos. Presentamos el caso de un niño de 2 años con el diagnóstico de una adenitis por Mycobacterium intracellulare que desarrolló una neutropenia grave secundaria a la terapia combinada de azitromicina y rifabutina oral. La metabolización hepática de los macrólidos parece aumentar la toxicidad de otros fármacos, en este caso, la rifabutina. Finalmente, al paciente se le realizó una exéresis quirúrgica por persistencia de la adenitis a pesar de la antibioterapia.

Riesgo cardiovascular con el uso de azitromicina / Cardiovascular risk with the azitromicina use

La azitromicina es un antibiótico macrólido semisintético de amplio espectro y de uso bien frecuente en la población mundial, indicado para el tratamiento de diferentes enfermedades infecciosas.1 Existen varios reportes del riesgo cardiovascular asociado al uso de azitromicina y aún no existen estudios convincentes del mecanismo molecular de este efecto.1,2 Un gran número de medicamentos se retiran del mercado por producir reacciones adversas cardiovasculares fatales, de ahí la importancia de comprender los mecanismos moleculares de la acción cardiovascular de los fármacos en desarrollo o de los que se comercializan en el mercado farmacéutico y más aún, aquellos de uso frecuente por la población. En el año 2011 la Administración de Alimentos y Medicamentos, (Food and Drug Administration , FDA), la agencia reguladora de los Estados Unidos revisó la información ofrecida en la etiqueta de los antibacterianos macrólidos, relacionada con la prolongación del intervalo QT y las arritmias cardiovasculares del tipo Torsades de Pointes (TdP), que incluye la nueva información acerca del riesgo de prolongación del intervalo QT, que parece ser bajo.3 Posteriormente, el 17 de mayo de 2012 al revisar la publicación de un artículo de Ray y colaboradores, la FDA advirtió a los profesionales de la salud que el antimicrobiano azitromicina, puede causar un ritmo cardíaco irregular potencialmente fatal en algunos pacientes, en función del estudio publicado por estos autores, sobre un pequeño aumento de la mortalidad y el riesgo de muerte en personas tratadas durante 5 días con azitromicina en comparación con las personas tratadas con amoxicilina, ciprofloxacino, o ningún fármaco.4 Desde el año 2012, la FDA hizo una advertencia en el etiquetado de los medicamentos que contenían azitromicina, basado en evidencias previas que indicaban riesgo cardiovascular asociado a su uso. Por otra parte, el Centro Colaborador de la Organización Mundial de la Salud (OMS) para la Vigilancia Farmacéutica Internacional radicado en Uppsala, Suecia (World Health Organization Collaborating Centre, The Uppsala Monitoring Centre for International Drug Monitoring), posee un registro de 100 casos con prolongación del segmento QT y unos 65 casos con TdP asociados al uso de azitromicina.5 El 12 de marzo de 2013 la FDA advirtió al público que la azitromicina...(AU)

Prevalencia de potenciales interacciones farmacológicas de Azitromicina en Colombia, 2012-2013 / Prevalence of potential drug interactions with azithromycin in Colombia, 2012-2013

Objetivos Determinar la prevalencia de potenciales interacciones farmacológicas entre azitromicina y diferentes antiarrítmicos del grupo IA y III en una base de datos de prescripción de medicamentos a nivel nacional durante el año 2012-2013. Métodos Estudio retrospectivo a partir de una base de datos poblacional de dispensación de medicamentos. Se extrajeron datos de los pacientes que recibieron azitromicina desde 1 de enero de 2012 a 30 junio de 2013, al igual que pacientes que recibieron este antibiótico en combinación a otros medicamentos con demostrado riesgo de provocar arritmias cardíacas al usarse concomitantemente. Se establecieron frecuencias y proporciones. Resultados Se identificaron 13 859 pacientes que recibieron azitromicina sola o en combinación con otros medicamentos. El tiempo promedio de uso fue 4,5±0,9 días; Un total de 702 pacientes (5,1 %) recibieron azitromicina más otros 19 fármacos de potencial riesgo. Los más frecuentemente asociados fueron: loratadina (77,1 %), difenhidramina (16,5 %) y amitriptilina (8,1 %). Las combinaciones con un solo medicamento fueron las más frecuentes (n=533, 75,9 %), con predominio de azitromicina+loratadina. El máximo número de fármacos combinados fue seis (n=2, 0,3 %). Conclusiones La identificación mediante bases de datos poblacionales la prescripción de medicamentos, es una manera eficaz de encontrar potenciales interacciones entre estos. La frecuencia de potenciales interacciones entre azitromicina y otros fármacos es común en pacientes colombianos. Se debe estimar el riesgo de ocurrencia de eventos cardiacos adversos.(AU)

Objective To determine the prevalence of potential drug interactions between azithromycin and different IA and III antiarrhythmic groups in a national database of drug prescriptions in 2012-2013. Methods Retrospective study based on a population database of medicine dispensation. Data from patients who received azithromycin between January 1, 2012 and June 30, 2013 were extracted along with data from patients who received azithromycin in combination with other medications shown to cause heart arrhythmias when used concomitantly. Frequencies and proportions were established. Results 13 859 patients receiving azithromycin alone or in combination with other drugs were identified. The average time of use was 4.5 ± 0.9 days. A total of 702 patients (5.1 %) received azithromycin plus 19 other potentially risky drugs. The most frequently associated were loratadine (77.1 %), diphenhydramine (16.5 %) and amitriptyline (8.1 %). Combinations with a single drug were the most frequent (n=533, 75.9 %), predominantly azithromycin+loratadine. The maximum number of combined drugs was six (n=2, 0.3 %). Conclusions Identification of drug prescriptions through population databases is an effective way to find potential drug interactions. The frequency of potential interactions between azithromycin and other drugs is common in Colombian patients. Future research should assess the risk of occurrence of adverse cardiac events.(AU)

Azitromicina y efectos cardiovasculares notificados al Sistema Cubano de Farmacovigilancia, 2003-2012 / Azithromycin and cardiovascular effects reported to ther Cuban System of Drug Surveillance in the period of 2003 through 2012

Introducción: la azitromicina, es un antibacteriano macrólido semisintético, al cual se han asociado efectos cardiovasculares, como la prolongación del intervalo QT y trastornos del ritmo que pueden ser fatales. La FDA alertó sobre un pequeño aumento de la mortalidad y riesgo de muerte en personas tratadas durante 5 días con este antibacteriano, y en el Centro Internacional de Monitoreo de Uppsala también se han registrado casos. Objetivo: caracterizar las reacciones adversas cardiovasculares a la azitromicina informadas a la Unidad Nacional Coordinadora de Farmacovigilancia durante el periodo 2003-2012. Métodos: estudio observacional, descriptivo y transversal utilizando la base de datos nacional de farmacovigilancia y las notificaciones espontáneas de reacciones adversas. Se trabajó con el universo de pacientes con reacciones adversas a la azitromicina. Las reacciones cardiovasculares se clasificaron según tipo de reacción, severidad, imputabilidad y frecuencia. Se estudiaron los pacientes que presentaron reacciones adversas según sexo y edad. RESULTADOS: se recibieron 1 960 notificaciones de reacciones adversas a la azitromicina en el periodo de estudio, de las cuales 96 se correspondieron con reacciones adversas cardiovasculares para el 4,9 por ciento. Predominaron en el sexo femenino (55,2 por ciento) y en los adultos (75 por ciento). Las palpitaciones representaron el 44,8 por ciento (43 pacientes), seguidas de la taquicardia y el dolor torácico. El 67,7 por ciento resultaron moderadas, el 71,9 por ciento probables y el 60,4 por ciento ocasionales. El 31,3 por ciento de las reacciones se pudo haber evitado y el motivo que predominó fue la indicación inadecuada en el 70 por ciento. CONCLUSIONES: aunque no se informan reacciones adversas cardiovasculares con desenlace fatal en personas tratadas con azitromicina, la tercera parte de ellas se podrían haber evitado; por lo se recomienda realizar una vigilancia más proactiva a este medicamento, así como informar todas las reacciones al Sistema Cubano de Farmacovigilancia(AU)

INTRODUCTION: azithromycin is a semisynthetic antimicrobial macrolide which is said to be associated with cardiovascular effects such as the prolongation of QT interval and disorders of the heart rate that may be fatal. The Food and Drug Administration has warned about a slight rise of mortality and risk of death in people treated for 5 days with this antibacterial drug; the International Center of Monitoring in Uppsala has also registered some cases.OBJECTIVE: to characterize the adverse cardiovascular reactions to azithromycin reported to the National Coordinating Unit of Drug Surveillance from 2003 through 2012. METHODS: observational, descriptive and cross-sectional study based on the national drug surveillance database and on the voluntary notifications of adverse reactions. The study universe was the patients with adverse reactions to azithromycin. The cardiovascular reactions were classified by type of reaction, severity, imputability and frequency. The patients presenting with adverse reactions were studied according to their sex and age. RESULTS: one thousand and nine hundred sixty adverse reactions to azithromycin were reported in the study period; 96 of them were cardiovascular reactions for 4.9 percent of the total amount. They were predominant in females (55.2 percent) and in adults (75 percent). Palpitations accounted for 44. 8 percent (43 patients) followed by tachycardia and chest pain. They were moderate in 67.7 percent of cases, probable in 71.9 percent and occasional in 60.4 percent. Regarding reaction, 31.3 percent of them could have been prevented and the predominant reason was the inadequate prescription of the drug in 70 percent of cases. CONCLUSIONS: although no adverse cardiovascular reactions causing death have been reported in individuals treated with azithromycin, one third of them could have been prevented, therefore it is recommended to perform more proactive surveillance on this drug and all types of reactions should be duly reported to the Cuban drug surveillance system(AU)

QT interval prolongation associated with azithromycin/methadone combination / Prolongación del intervalo QT asociada con combinación de azitromicina/metadona

This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes.

Este reporte documenta la ocurrencia de la prolongación del intervalo QT en un hombre de 57 años, en la terapia de reemplazo con metadona, tratado con azitromicina por pulmonía adquirida en la comunidad. Este caso destaca una interacción de medicamentos desconocida hasta ahora. En vista del uso cada vez mayor de la azitromicina, resulta absolutamente necesario usarla con precaución en pacientes que ya están bajo tratamiento con medicamentos de los cuales se sabe que causan prolongación del intervalo QT o que causan torsades de pointes.

Comparison of efficacy of azithromycin vs. clindamycin and erythromycin in the treatment of mild to moderate acne vulgaris

Acne vulgaris is a prevalent inflammatory skin disorder. Topical solutions of clindamycin and erythromycin are the most common treatment in the patients. This study was conducted to compare the effect of topical solution azithromycin as a new method of treatment against topical solutions of clindamycin and erythromycin. A randomized double-blind clinical trial was carried out for 20 weeks at the outpatient clinics of Boo-Ali Sina Hospital in Sari [Iran] on 96 patients with mild to moderate acne vulgaris. They were randomly divided in three groups who were matched together based on -Acne Severity Index [ASI] and were treated with 2% alcoholic solution of azithromycin, erythromycin and clindamycin respectively twice daily for 16 weeks. Treatment efficacy was determined by Total acne Lesion Counting [TLC]. For each three treatment groups, decreased TLC and ASI were significant at the end of 16 weeks [P<0.05]. Azithromycin was more effective than the clindamycin and erythromycin for acne therapy after 16 weeks [P<0.05]. Twenty patients [20.8%] of azithromycin group [12.5%] reported to have adverse effects, such as erythema and/or pruritus [P<0.05]. Topical solution azithromycin is a more effective treatment for mild to moderate acne vulgaris comparing to clindamycin and erythromycin, but it has more local side effects

Eficácia da azitromicina no tratamento da periodontite agressiva / Effectiveness of the azitromicin in the treatment of aggressive periodontitis

Foi feita uma revisão bibliográfica sobre o uso da azitromicina em Periodontia considerando algumas questões como: Pode este antibiótico aumentar o efeito da raspagem radicular, limitar seus efeitos adversos ou pode até mesmo ser um substituto em alguns casos? A azitromicina vem sendo associada, em alguns casos, à raspagem e ao alisamento radicular no tratamento de doenças periodontais agressivas, por ser eficaz no combate a bactérias periodontopatogênicas. No entanto, faltam estudos com conteúdo confiável para se confirmar o sucesso dessa nova terapia. Sendo assim, o tratamento principal para a periodontite agressiva continua sendo a raspagem e o alisamento radicular.

Suscetibilidade à azitromicina de agentes bacterianos isolados de processos infecciosos em diferentes sítios de animais de companhia / Azithromycin susceptibility pattern of bacterial isolated from different sites of infections in pet animals

Avaliou-se o perfil de suscetibilidade bacteriana de diferentes sítios infecciosos frente aos antimicrobianos de eleição e determinaram-se o perfil de atividade in vitro e a concentração inibitória mínima (CIM) da azitromicina. Diferentes testes fenotípicos detectaram resistência à azitromicina em 45 por cento de Staphylococcus spp. e 65 por cento dos bastonetes Gram-negativo. A CIM50 para S. aureus foi 4,0μg/mL para S. intermedius 1,0μg/mL, Staphylococcus spp. coagulase-negativo >512μg/mL e bastonetes Gram-negativo 256μg/mL. Investigou-se, também, uma possível resistência cruzada entre oxacilina e azitromicina por meio da detecção do gene mecA em Staphylococcus spp. Foi possível detectar resistência à azitromicina em nove (15 por cento) isolados de Staphylococcus spp. mecA positivo.

Antimicrobials susceptibility pattern of bacterial isolated from different sites of infection, in vitro azithromycin activity pattern, and its minimum inhibitory concentration (MIC) values were evaluated. Different phenotypic tests detected azithromycin resistance in 45 percent of Staphylococcus spp. and 65 percent of resistant Gram-negative rods. MIC50 was 4.0μg/mL for Staphylococcus aureus, 1.0μg/mL for S. intermedius, >512.0μg/mL for coagulase negative Staphylococcus, and 256.0μg/mL for Gram-negative rods. In addition, it was investigated the possible cross-resistance between oxacillin and azithromycin, by detection of mecA gen in Staphylococcus spp. Nine (15 percent) mecA-positive Staphylococcus spp. were also phenotypically resistant to azithromycin.

Suscetibilidade à azitromicina de isolados bacterianos de processos infecciosos em cães e gatos / Susceptibility to azithromycin of bacteria isolated from infectious processes in dogs and cats

O presente estudo avaliou o perfil de suscetibilidade à azitromicina de patógenos bacterianos prevalentes em diferentes sítios infecciosos de animais de companhia. Adicionalmente, foram estudados o perfil de atividade in vitro de azitromicina contra esses patógenos e sua concentração inibitória mínima (CIM). Testes como a difusão em disco e a microdiluição em caldo detectaram resistência respectivamente em 48,6 por cento e 55 por cento dos isolados de Staphylococcus spp. e em 55,3 por cento e 72,7 por cento dos bastonetes Gram-negativos. A CIM50 para S. aureus foi 4,0mg/mL, para S. intermedius foi de 1,0mg/mL, para Staphylococcus spp. coagulase-negativas foi de e"512mg/mL e para bastonetes Gram-negativos foi de 256mg/mL. Quinze por cento (9/60) dos isolados oxacilina-resistente e multidroga-resistentes, mecA-positivos, de Staphylococcus spp. apresentaram também resistência à azitromicina. A disseminação de bactérias multidroga-resistentes aponta para a necessidade da avaliação da atividade antimicrobiana para selecionar o fármaco mais indicado e, assim, minimizar falhas terapêuticas na conduta clínica veterinária.

The susceptibility pattern to azithromycin of bacterial pathogens from various infectious sites, and the in vitro activity and minimum inhibitory concentration (MIC) of azithromycin were studied. Tests such as disc diffusion and broth microdilution detected respectively 48.6 percent and 55 percent of resistant Staphylococcus spp., and 55.3 percent and 72.7 percent resistant gram-negative rods. MIC50 for S. aureus was 4.0mg/mL, that for S. intermedius was 1.0mg/mL, for coagulase-negative Staphylococcus e"512mg/mL, and for gram-negative rods 256mg/mL. Fifteen percent (9/60) of oxacilin-resistant, multidrug-resistant and mecA-positive Staphylococcus spp. isolates were also azithromycin resistant. The dissemination of multidrug resistant bacteria points out to the need of antimicrobial evaluation activity in order to select the best indicated drug and thus minimizing therapeutic failures in veterinary practice.

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil / Falha da azitromicina e do antimonial no tratamento da leishmaniose cutânea em Manaus, AM, Brasil

A non-randomized controlled clinical trial was carried outin order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5 percent) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5 percent) cases. In group II, antimony cured eight of 19 (42.1 percent) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9 percent) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

Com o objetivo de avaliar a eficácia da azitromicina no tratamento da leishmaniose cutânea, foi realizado ensaio comparativo, em Manaus. Foram recrutados 49 pacientes de ambos os sexos, com idades entre 14 e 70 anos que apresentassem úlceras cutâneas com menos de três meses de evolução e que tivessem exame direto positivo para amastigotas de leishmânia. Estes pacientes foram alocados em dois grupos assim: Grupo I (26) recebeu uma dose diária de 500 mg de azitromicina pela via oral durante 20 dias e o Grupo II, recebeu uma dose diária de 20 mg/kg de antimoniato de meglumina por via intramuscular, durante 20 dias. Do grupo da azitromicina, três (12,5 por cento) de 24 pacientes curaram 60, 90 e 120 dias, respectivamente, enquanto, em 21 (87,5 por cento) de 24 houve falha terapêutica. No grupo do antimonial, oito (42,5 por cento) de 19 pacientes curaram como segue: três no dia 30, um no dia 60, um no dia 90 e três no dia 120. Contudo, em 11 (57,9 por cento) de 19 casos, houve falha terapêutica. A azitromicina foi menos eficaz do que o antimonial, embora, a análise da taxa de resposta por intenção de tratamento não mostrou diferença significativa, entre eles. A azitromicina foi melhor tolerada; porém, mostrou-se pouco eficaz no tratamento da leishmaniose cutânea, em Manaus.