[Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab]. / Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab.

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.

Aftas orales refractarias en tratamiento con adalimumab y apremilast en paciente con enfermedad de Behçet. Informe de un caso / Refractory oral aftas in treatment with adalimumab and apremilast in patient with Behçet syndrome. A case report

La enfermedad de Behçet es un trastorno inflamatorio multisistémico que se manifiesta de forma muy variada a nivel cutáneo, especialmente en forma de aftas orales frecuentemente refractarias. Los tratamientos con utilidad en la sintomatología de esta patología, resultan poco específicos y poco efectivos; teniendo que recurrir a veces a tratamientos sistémicos, como los biológicos: entre ellos, los anti-TNFα. Presentamos el caso de una paciente con enfermedad de Behçet, con aftas orales severas, recurrentes y refractarias a múltiples tratamientos. Actualmente, la paciente ha alcanzado la remisión clínica en tratamiento combinado de adalimumab y apremilast. (AU)

Behçet’s disease is a multisystemic inflammatory disorder that manifests itself in a variety of ways at the cutaneous level, especially in the form of oral thrush, very often very refractory. Treatments that are useful in the symptomatology of this pathology are not very specific and not very effective; sometimes it is necessary to resort to systemic treatments, such as biologi-cal ones: among them, anti-TNFα.We present the case of a patient diagnosed with Behçet’s disease, with severe oral aphthae, very recurrent and refractory to multiple treatments. Currently, the patient has reached clinical remission in combined treatment of adalimumab and apremilast. (AU)

Efecto de los fármacos modificadores del PH sobre los inhibidores de la tirosin quinasa: contrastando información / Effect of gastric-acid-reducing agents on the tyrosine kinasa inhibitors: contrasting information

Objetivos: Los inhibidores de la tirosin quinasa (ITK) comprenden un conjunto de moléculas ampliamente utilizadas actualmente en onco-hematología. Los ITK han supuesto una ventaja para los pacientes, de forma que la administración oral favorece su autonomía, pero a su vez, su absorción gastrointestinal y, por ende, su biodisponibilidad, puede verse alterada por el PH-gástrico. Las interacciones con los fármacos modificadores del PH son un problema conocido y una consulta frecuente. El objetivo del estudio fue analizar las interacciones ITK-fármacos modificadores del PH-gástrico y las discrepancias en diferentes bases de datos. Con los resultados, se elaboró una tabla, para proporcionar a los pacientes la información correcta y consensuada, y no generar así inseguridad que comprometa la adherencia al tratamiento o confianza hacia el profesional sanitario. Métodos: Se exportaron de la web de la Agencia Española del Medicamento y Productos Sanitarios los fármacos clasificados como ITK directos (ATC: L01XE). Se consultó la interacción de éstos con los IBP, Anti-H2 y antiácidos en diversas fuentes y se resumieron los hallazgos.Resultados y conclusiones: Para establecer una fuerte recomendación, es necesario consultar varias bases de datos, ya que las discrepancias o la información insuficiente pueden llevar a recomendaciones erróneas. Es importante establecer un consenso entre profesionales para realizar la recomendación correcta, y no ver comprometida la eficacia del tratamiento, con las importantes consecuencias que ello conllevaría. (AU)

Objectives: Tyrosine kinase inhibitors (TKIs) include a group of molecules widely used in oncohematology today. Using the oral administration route of TKIs offers an advantage for the patient; favoring patient autonomy, however, oral administration also causes relevant new problems. Gastrointestinal absorption and, therefore, bioavailability, can be altered by gastric PH. Interactions of these TKIs with gastric acid reducing (GAR) drugs are a known problem and a frequent query in clinical practice. The aim was to analyze ITK-GAR drugs interactions and discrepancies in different databases. Based on the results, a table was elaborated to provide the correct and consensed information, and thus not generate insecurity that compromises the adherence to the treatment or trust towards the healthcare professional.Methods: Drugs classified as direct ITKs (ATC: L01XE) were exported from the Spanish Agency for Medicines and Health Products website. Their interaction with PPIs, Anti-H2 and antacids was consulted in different databases and findings were summarized.Results and conclusions: To establish a strong recommendation, it is necessary to consult several databases, because of discrepancies or insufficient information can lead to erroneous recommendations. It is important to establish a consensus among professionals to make the correct recommendation, and not compromising the effectiveness of the treatment, which would entail important consequences. (AU)

Monitorización farmacocinética de niveles supraterapéuticos de adalimumab en paciente con enfermedad de Crohn / Pharmacokinetic monitoring of supratherapeutic adalimumab levels in patient with Crohn's disease

La monitorización farmacocinética de terapias biológicas dirigidas frente al factor de necrosis tumoral-a (TNF-a) ha sido recientemente introducida en nuestro centro hospitalario gracias a la iniciativa de nuestro equipo de enfermedad inflamatoria intestinal, formado por farmacéuticos, digestólogos y analistas clínicos, con la finalidad de optimizar la terapia en los pacientes que se mantienen en remisión clínica (monitorización "pro-activa"), o que presentan un fracaso terapéutico (monitorización "re-activa"). Se presenta un caso clínico de una paciente diagnosticada de enfermedad de Crohn y en tratamiento combinado con metotrexato y adalimumab. En septiembre de 2018, adalimumab fue intensificado de forma empírica a dosis de 40 mg administrados semanalmente por la aparición de manifestaciones extradigestivas (artralgias y parestesias en miembros inferiores). En febrero de 2019, la paciente se mantenía en remisión clínica con respecto a los síntomas intestinales, pero continuaba con las manifestaciones extradigestivas y refería aftas orales recurrentes. Por este motivo, se monitorizaron los niveles séricos de adalimumab, los cuales superaron ampliamente el intervalo terapéutico recomendado (5-12 mig/ml). En este sentido, se describe el seguimiento multidisciplinar del caso clínico y el ajuste posológico realizado en base a predicciones bayesianas, principios farmacocinéticos y farmacodinámicos y la clínica de la paciente. La monitorización farmacocinética de los niveles supraterapéuticos de adalimumab fue una herramienta útil para la optimización de dosis de adalimumab y la valoración objetiva de reacciones adversas en esta paciente. Este caso se ha notificado al Sistema Español de Farmacovigilancia

The pharmacokinetic monitoring of biological therapies against tumor necrosis-a (TNF-a) was recently introduced at our hospital thanks to the initiative of our inflammatory bowel disease team, composed of specialists in pharmacology, digestive system disease, and clinical analysis. The aim of the program was to optimize the therapy delivered to patients in clinical remission (pro-active monitoring) or clinical failure (reactive monitoring). We report the case of a patient diagnosed with Crohn's disease and under combined treatment with methotrexate and adalimumab. In September 2018, the dose of adalimumab was empirically increased to 40 mg/week due to the onset of extraintestinal manifestations (arthralgias and paraesthesias in lower limbs). In February 2019, the patient was in clinical remission with respect to the intestinal symptoms, but the extraintestinal manifestations persisted and the patient also reported anal aphthae. Consequently, serum adalimumab concentrations were monitored and found to widely exceed the recommended therapeutic interval (5-12 mig/ml). We report the multidisciplinary follow-up of the clinical case and the dosage adjustment based on Bayesian predictions, pharmacokinetic and pharmacodynamic principles, and the patient's clinical situation. Pharmacokinetic monitoring of supratherapeutic adalimumab levels proved to be a useful tool to achieve the optimal dosage of this drug and to objectively evaluate the patient's adverse reactions. The Spanish Pharmacosurveillance System has been notified of this case

¿Son las bases de datos bibliográficas una buena fuente de la evidencia científica en la retiradade fármacos del mercado? / Are scientific literature databases a good source of scientific evidence for discontinuing a drug form the market?

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Volumen de dilución de fármacos intravenosos en pacientes con restricción de fluidos / Dilution volume of intravenous drugs in patients under fluid restriction therapy

Introducción: El mantenimiento del equilibrio hidroelectrolítico es esencial para el buen funcionamiento del organismo. Existen situaciones en las que se producen desequilibrios en los líquidos corporales, originando sobrecargas de fluidos, y sus consecuentes problemas asociados. Los pacientes con esta problemática, pueden beneficiarse de la administración de fármacos parenterales en el menor volumen posible. Los pacientes en estado crí- tico suelen requerir un gran número de fármacos por vía intravenosa, y altas dosis de éstos a diluir en grandes cantidades de suero. Por todo ello, parece útil buscar una estrategia de optimización de la administración de los fármacos parenterales. Objetivo: Revisar y recopilar datos referentes a volúmenes mí- nimos de dilución. Además de las vías de administración, reconstitución, diluyentes compatibles, tiempos de infusión. Método: Se incluyeron en el estudio aquellos principios activos utilizados con más frecuencia en pacientes críticos. Se realizó una búsqueda en varias fuentes de información: fichas técnicas de las especialidades farmacéuticas, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare series, o vía telefónica con el laboratorio fabricante del producto. Resultados: Los resultados se muestran en forma de tabla. Se revisaron 65 especialidades farmacéuticas. Conclusiones: Consideramos útil la recopilación de estos datos para optimizar la administración parenteral en pacientes críticos o que requieran una terapia restrictiva en fluidos ya que la información ha tenido que ser recopilada de distintas fuentes no encontrándose siempre en la ficha técnica. (AU)

Introduction: A fluid and electrolyte balance is essential for human health. There are some situations in which fluid imbalance occurs, causing fluid overload and consequent associated problems. Patients with these problems, may benefit from the administration of parenteral drugs in the smallest possible volume. Patients in critical condition typically require a large number of drugs intravenously, and high doses of these diluted in large quantities of serum. Therefore, it seems useful to seek an optimization strategy of parenteral drug administration. Objective: To review and collect data on minimum dilution volumes. Besides administration s routes, recons - titution, compatible diluents, infusion times. Methods: The study included those drug substances frequently used in critically ill patients. A search through multiple sources of information has been made: technical data for Propietary medicinal products, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare Series, or by phone calls to the manufacturers of the product. Results: Results are shown in a table. 65 drugs were revised. Conclusions: It is considered useful the collection of these data to optimize parenteral administration in critically ill patients, or in those who require restrictive fluid therapy, because information has been collected from different sources, not always found it in the technical data of the drugs (AU)

[Dilution volume of intravenous drugs in patients under fluid restriction therapy]. / Volumen de dilución de fármacos intravenosos en pacientes con restricción de fluidos.

INTRODUCTION: A fluid and electrolyte balance is essential for human health. There are some situations in which fluid imbalance occurs, causing fluid overload and consequent associated problems. Patients with these problems, may benefit from the administration of parenteral drugs in the smallest possible volume. Patients in critical condition typically require a large number of drugs intravenously, and high doses of these diluted in large quantities of serum. Therefore, it seems useful to seek an optimization strategy of parenteral drug admi - nistration. OBJECTIVE: To review and collect data on minimum dilution volumes. Besides administration s routes, reconstitution, compatible diluents, infusion times. METHODS: The study included those drug substances frequently used in critically ill patients. A search through multiple sources of information has been made: technical data for Propietary medicinal products, Handbook on Injectable Drugs, Trissel L., American Society Healh-System Pharmacists, 15thEd., 2009, Thomson Micromedex® Healthcare Series, or by phone calls to the manufacturers of the product. RESULTS: RESULTS are shown in a table. 65 drugs were revised. CONCLUSIONS: It is considered useful the collection of these data to optimize parenteral administration in critically ill patients, or in those who require restrictive fluid therapy, because information has been collected from different sources, not always found it in the technical data of the drugs.