Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas / Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to drug-drug interactions

Objetivo: evaluar el perfil de seguridad de nirmatrelvir-ritonavir (NMV-r) en la práctica clínica real y analizar la relevancia clínica de las interacciones farmacológicas en el desarrollo de eventos adversos. Material y métodos: estudio observacional, retrospectivo en el que se evaluaron los datos de seguridad de pacientes tratados con NMV-r entre abril y julio de 2022. Se recopilaron datos demográficos y analíticos antes de comenzar el tratamiento. La duración del seguimiento fue de 28 días y se evaluó el número reacciones adversas reportadas, así como si fueron manejadas de forma ambulatoria o precisaron de asistencia sanitaria especializada y la presencia de deterioro de la función renal y hepática. Se revisó el tratamiento concomitante, identificando interacciones farmacológicas teóricas (IFT) cuya gravedad fue definida mediante la clasificación Lexi-interact. Resultados: el estudio incluyó 146 pacientes, 82 (56,16 %) eran mujeres, cuya mediana de edad fue de 65 años (22-95). El número de IFT detectadas y mantenidas durante el tratamiento con NMV-r fue de 164, siendo el porcentaje de pacientes con al menos una interacción de 62,33%. La mediana de IFT por paciente fue de uno (0-5). En 18 pacientes (11,84%) se reportó al menos un evento adverso (EA). Once EA se relacionaron potencialmente con alguna IFT, 7 pacientes requirieron contacto con asistencia hospitalaria para el manejo del EA, 8 pacientes presentaron deterioro de la función renal y 2 de la función hepática a los 28 días. Los principales grupos de fármacos implicados en la aparición de algún EA fueron los anticoagulantes orales, así como los calcio-antagonistas. Conclusiones: nuestros resultados muestran un elevado número de IFT detectadas entre NMV-r y otros fármacos, aunque la frecuencia de EA asociados fue baja. Este estudio proporciona un mayor conocimiento de los fármacos implicados en dichas interacciones y su potencial relación con la aparición de EA.(AU)

Objective: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. Methods: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. Results: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. Conclusions: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.(AU)

Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to DDIs / Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas

Objetivo: evaluar el perfil de seguridad de nirmatrelvir-ritonavir (NMV-r) en la práctica clínica real y analizar la relevancia clínica de las interacciones farmacológicas en el desarrollo de eventos adversos. Material y métodos: estudio observacional, retrospectivo en el que se evaluaron los datos de seguridad de pacientes tratados con NMV-r entre abril y julio de 2022. Se recopilaron datos demográficos y analíticos antes de comenzar el tratamiento. La duración del seguimiento fue de 28 días y se evaluó el número reacciones adversas reportadas, así como si fueron manejadas de forma ambulatoria o precisaron de asistencia sanitaria especializada y la presencia de deterioro de la función renal y hepática. Se revisó el tratamiento concomitante, identificando interacciones farmacológicas teóricas (IFT) cuya gravedad fue definida mediante la clasificación Lexi-interact. Resultados: el estudio incluyó 146 pacientes, 82 (56,16 %) eran mujeres, cuya mediana de edad fue de 65 años (22-95). El número de IFT detectadas y mantenidas durante el tratamiento con NMV-r fue de 164, siendo el porcentaje de pacientes con al menos una interacción de 62,33%. La mediana de IFT por paciente fue de uno (0-5). En 18 pacientes (11,84%) se reportó al menos un evento adverso (EA). Once EA se relacionaron potencialmente con alguna IFT, 7 pacientes requirieron contacto con asistencia hospitalaria para el manejo del EA, 8 pacientes presentaron deterioro de la función renal y 2 de la función hepática a los 28 días. Los principales grupos de fármacos implicados en la aparición de algún EA fueron los anticoagulantes orales, así como los calcio-antagonistas. Conclusiones: nuestros resultados muestran un elevado número de IFT detectadas entre NMV-r y otros fármacos, aunque la frecuencia de EA asociados fue baja. Este estudio proporciona un mayor conocimiento de los fármacos implicados en dichas interacciones y su potencial relación con la aparición de EA.(AU)

Objective: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. Methods: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. Results: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. Conclusions: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.(AU)

[Translated article] Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to DDIs.

OBJECTIVE: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyse the clinical relevance of drug-drug interactions in the development of adverse events. METHODS: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. RESULTS: The study included 146 patients. 82 (56.16%) were women, whose median age was 65 years (22-95). the number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least 1 interaction being 62.33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11.84%). 11 AEs were potentially related to any TDDI. 7 patients required contact with hospital assistance for AE management. 8 patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. CONCLUSIONS: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.

[Translated article] Influence of augmented renal clearance in the lower incidence of linezolid-related haematological toxicity.

OBJECTIVES: Linezolid is an oxazolidin commonly related to the development of haematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced haematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. MATERIAL AND METHODS: A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014-2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60-90 mL/min) were compared. Haematological toxicity was defined as a decrease of 25% in platelets, of 25% in haemoglobin, and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of haematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentage diminution of all 3 parameters was calculated and compared by Mann-Whitney test and treatment interruption and transfusion requirements were registered. RESULTS: 30 ARC patients and 38 reference patients were included. Haematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (P=.014); thrombocytopenia in 13.33% vs 36.84% (P=.051), anaemia in 3.3% vs 10.52% (P=.374) and neutropenia in 10% vs 23.68% (P=.204). Median percentage of platelets decrease in ARC patients was -10.36 (-193.33-62.03) vs 2.68 (-163.16-82.71) in reference patients (P=.333), while haemoglobin decrease was 2.50 (-12.12-25.93) vs 9.09 (-17.72-30.63) (P=.047) and neutrophils decrease was 9.14 (-73.91-76.47) vs 27.33 (-86.66-90.90) (P=.093). 10.5% of normal renal function patients reported at least 1 adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had transfusion requirements. No major events or interruptions were reported in ARC patients. CONCLUSION: Our findings suggest a lower incidence and clinical relevance of haematological toxicity in augmented renal clearance patients. Thrombocytopenia was the major event in both populations. This might be related to a lower exposure to the drug due to the higher clearance and likely lower therapeutic efficiency. These results suggest a potential benefit of therapeutic drug monitoring on high risk patients.

Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to drug-drug interactions. / Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas.

OBJECTIVE: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. METHODS: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. RESULTS: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. CONCLUSIONS: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.

Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid / Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity

Objetivos linezolid es una oxazolidina frecuentemente implicada en el desarrollo de toxicidad hematológica, siendo el aclaramiento renal el mecanismo mayoritario en su eliminación. Se evaluó la influencia de la hiperfiltración glomerular en la toxicidad hematológica inducida por linezolid en pacientes con aclaramiento incrementado frente a pacientes con función renal normal. Material y métodos se diseñó un estudio observacional y retrospectivo en pacientes hospitalizados, tratados al menos 5 días con linezolid entre 2014 y 2019. Se compararon pacientes con aclaramiento de creatinina incrementado (≥130 mL/min) y normal (60–90 mL/min). Se definió la toxicidad hematológica como el descenso en plaquetas y hemoglobina del 25% y en neutrófilos del 50% frente a los valores basales. Se clasificó el grado de toxicidad según Common Terminology Criteria for Adverse Events v5 y se comparó la incidencia entre ambos grupos mediante Chi-cuadrado y Fisher. Así mismo, se calculó el porcentaje de disminución de los 3 parámetros y su asociación mediante el test de Mann–Whitney y se registraron las interrupciones y transfusiones asociadas.Resultados se evaluaron 30 pacientes hiperfiltradores y 38 normofiltradores. El 16,66% de hiperfiltradores presentó toxicidad hematológica frente al 44,74% (p = 0,014). La trombocitopenia fue del 13,33 vs. 36,84% (p = 0,051), la anemia del 3,3 vs. 10,52% (p = 0,374) y la neutropenia del 10 vs. 23,68% (p = 0,204). La mediana del porcentaje de descenso plaquetario en hiperfiltradores frente a normofiltradores fue del −10,36 (−193,33–62,03) vs. 2,68 (−163,16–82,71) (p = 0,333), de hemoglobina 2,50 (−12,12–25,93) vs. 9,09 (−17,72–30,63) (p = 0,047) y de neutrófilos 9,14 (−73,91–76,47) vs. 27,33 (−86,66–90,90) (p = 0,093). El 10,5% con filtrado normal presentó toxicidad grado 3 o superior, el 2,6% interrumpió el tratamiento y el 5,2% requirieron transfusiones... (AU)

Objectives Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. Material and methods A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014–2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60–90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann–Whitney test and treatment interruption and tranfusion requirements were registered. Results 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was −10.36 (−193.33–62.03) vs 2.68 (−163.16–82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (−12.12–25.93) vs 9.09 (−17.72–30.63) (p = 0.047) and neutrophils decrease was 9.14 (−73.91–76.47) vs 27.33 (−86.66–90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements... (AU)

Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity. / Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid.

OBJECTIVES: Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. MATERIAL AND METHODS: A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014-2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60-90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann-Whitney test and treatment interruption and tranfusion requirements were registered. RESULTS: 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was -10.36 (-193.33-62.03) vs 2.68 (-163.16-82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (-12.12-25.93) vs 9.09 (-17.72-30.63) (p = 0.047) and neutrophils decrease was 9.14 (-73.91-76.47) vs 27.33 (-86.66-90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements. No major events or interruptions were reported in ARC patients. CONCLUSION: Our findings suggest a lower incidence and clinical relevance of hematological toxicity in augmented renal clearance patients. Thrombocytopenia was the major event in both populations. This might be related to a lower exposure to the drug due to the higher clearance and likely lower therapeutic efficiency. These results suggest a potential benefit of therapeutic drug monitoring on high risk patients.

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness.

OBJECTIVE: To study immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab, as well as to assess whether these reactions could be predictors of further effectiveness of therapy. METHODS: Retrospective, observational and longitudinal study. All NSCLC patients who received nivolumab between February 2015-May 2020 were included. In terms of safety, irAEs and their severity were registered and to evaluate the effectiveness, overall survival (OS) and progression free survival (PFS) were calculated. RESULTS: 75 patients were included. 32 patients (43%) were reported irAES. Mainly the irAEs affected the skin (36%). Followed by pneumonitis (20%), gastrointestinal reactions (12%), endocrine (12%) and hepatitis (12%). Regarding severity, 92% were moderate. The median PFS was 9.49 months on the group with irAEs versus 1.99 months on the group without irAEs group (p < 0.0001). The median OS was 17.44 months versus 7.67 months respectively (p = 0.0001). According to the incidence of irAEs developed ( = > 2 vs. 1 vs. 0), the median PFS was 20.53 versus 5.35 versus 1.99 months respectively (p < 0.0001). The median OS was 23.41 versus 15.80 versus 7.67 months, respectively (p = 0.0002). CONCLUSION: In a significant number of patients irAEs occur, generally of grade 1-2 severity, affecting mainly the skin, lungs and gastrointestinal system. We confirm that the development of irAEs in patients with NSCLC treated with nivolumab is a strong predictor of treatment effectiveness in both PFS and OS, with statistically significant results. On those patients who experience two or more immunorelated adverse events the greatest benefit has been observed.

Efectividad y seguridad del tratamiento de las enfermedades de depósito lisosomal: análisis de 22 pacientes / Effectiveness and safety of the treatment of lysosomal deposit diseases: Analysis of 22 patients

Objetivos: Los objetivos son: identificar variables de eficacia empleadas en fármacos para enfermedades de depósito lisosomal (EDL), evaluar la calidad de esta evidencia, y conocer la efectividad y seguridad de estos tratamientos.Material y métodosEstudio observacional retrospectivo que incluyó pacientes con EDL tratados con terapia de sustitución enzimática (TSE) o de reducción de sustrato (TRS). Se revisaron los ensayos clínicos (EC) publicados y guías de tratamiento de EDL para seleccionar las variables de eficacia. Se obtuvieron los datos para medirlas (y efectos adversos) de la historia clínica.ResultadosNo se encontraron EC en los que se evalúe la eficacia con variables finales, todas fueron subrogadas. Se incluyeron 22 pacientes: 8 con enfermedad de Gaucher, 6 con enfermedad de Niemann-Pick tipo C, 2 con enfermedad de Hunter, uno con enfermedad de Morquio-A y 5 con enfermedad de Pompe. Ocho pacientes respondieron a TSE y uno a TRS. La TSE no se relacionó con efectos adversos. Miglustat produjo problemas de tolerancia que requirieron cambio de tratamiento en un paciente.ConclusionesLa efectividad fue variable según la enfermedad. Respecto a seguridad, se asociaron reacciones adversas a TRS manejables con ajustes posológicos. (AU)

Objectives: Identify the efficacy variables collected in the literature for therapies used in lysosomal storage diseases (LDS), evaluate the quality of this evidence, and know the effectiveness and safety of these treatments.Material and methodsRetrospective observational study that included patients with LDS treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Published clinical trials (CT) and LDS treatment guidelines were reviewed to select efficacy variables. Data to measure them (and adverse effects) were obtained from the medical history.ResultsNo CTs have been found in which efficacy is evaluated with final variables, all have been surrogated. Twenty-two patients were included: eight with Gaucher disease, six with Niemann–PickC disease, two with Hunter disease, one with Morquio-A disease, and five with Pompe disease. Eight patients have responded to ERT and one to SRT with eliglustat. ERT has not been associated with adverse effects. Miglustat has produced tolerance problems, requiring a change in a patient.ConclusionsThe effectiveness was variable according to the pathology. Regarding safety, manageable adverse reactions to SRT were associated with dosage adjustments. (AU)

Effectiveness and safety of the treatment of lysosomal deposit diseases: Analysis of 22 patients. / Efectividad y seguridad del tratamiento de las enfermedades de depósito lisosomal: análisis de 22 pacientes.

OBJECTIVES: Identify the efficacy variables collected in the literature for therapies used in lysosomal storage diseases (LDS), evaluate the quality of this evidence, and know the effectiveness and safety of these treatments. MATERIAL AND METHODS: Retrospective observational study that included patients with LDS treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Published clinical trials (CT) and LDS treatment guidelines were reviewed to select efficacy variables. Data to measure them (and adverse effects) were obtained from the medical history. RESULTS: No CTs have been found in which efficacy is evaluated with final variables, all have been surrogated. Twenty-two patients were included: eight with Gaucher disease, six with Niemann-PickC disease, two with Hunter disease, one with Morquio-A disease, and five with Pompe disease. Eight patients have responded to ERT and one to SRT with eliglustat. ERT has not been associated with adverse effects. Miglustat has produced tolerance problems, requiring a change in a patient. CONCLUSIONS: The effectiveness was variable according to the pathology. Regarding safety, manageable adverse reactions to SRT were associated with dosage adjustments.

[Lean Six Sigma in the implementation of automated dispensing systems: improving the safe use of medications in thoracic surgery.] / Lean Seis Sigma en la implantación de sistemas automatizados de dispensación: mejora del uso seguro del medicamento en cirugía torácica.

OBJECTIVE: Medications errors are a major problem that can cause a harm to inpatients. The main objective of the study was to compared medication errors in pharmacotherapeutic process before and after to carried out an intervention: to implant an automated dispensing cabine with to use Lean Six Sigma methodology. The secondary objective was to assess process performance, sigma level and defects per one million opportunities for medication error. METHODS: Quasi-experimental and randomized study carried out in a Thoracic Surgery Unit of a Spanish Hospital. A pharmaceutic recorded and assesed the medication errors detected during pre-intervention period (july-august 2017) and post-intervention period (march-april 2018). The steps analyzed were dispensing, storage and compounding/administration. The pharmacist observed a third of the medication dispensed, stored and compounded/administered during the study period. The observed medication was randomly selected using AleatorMetod.xls software. To perform the statistical analysis, Student's t test and Mann-Whitney U test were used to compare quantitative variables, and Chi-square test for qualitative variables. A significance level of p<0.05 was considered. RESULTS: The pharmaceutic recorded 4,538 drugs. After intervention, medication errors were decreased a 49% in total pharmacotherapeutic process (12.06% vs 6.15%; p<0.001). In addition, errors were decreased a 91.6% (4.27% vs 0.36%; p=0.004) in the step of medication storage; and a 75.8% (22.52% vs 5.46%; p<0.001) in the step of drugs compounding/administration. However, medication errors were increased in the step of medication dispensing (4.51% vs 15.29%; p<0.001). The process performance increased a 6% (87.9% vs 93.9%), sigma level increased from 2.67 to 3.04 and defects per one million opportunities for medication error decreased a 49%. CONCLUSIONS: To implant an automated dispensing cabinet with Lean Six Sigma methodology helps create a safer environment for the inpatient, reducing medication errors in the steps of storage and preparation/administration, as well as improving the total process performance and sigma level.

OBJETIVO: Los errores de medicación son un problema importante que pueden provocar un daño en los pacientes hospitalizados. El objetivo principal del estudio fue evaluar los errores de medicación en el circuito farmacoterapéutico antes y después de realizar una intervención: implantación de un Sistema Automatizado de Dispensación con la utilización de metodología Lean Seis Sigma. El objetivo secundario fue evaluar el rendimiento del proceso, el nivel sigma y los defectos por millón de oportunidades de error en la medicación. METODOS: Estudio cuasi-experimental y aleatorizado realizado en la Unidad de Cirugía Torácica de un Hospital Español. Un farmacéutico registró y evaluó los errores detectados durante las fases pre-intervención (julio-agosto 2017) y post-intervención (marzo-abril 2018). Las etapas analizadas fueron dispensación, almacenaje y preparación/administración. El farmacéutico observó un tercio de la medicación dispensada, almacenada y preparada/administrada durante el periodo de estudio. La medicación observada fue seleccionada de forma aleatoria utilizando el software AleatorMetod.xls. Para realizar el análisis estadístico se utilizó la prueba t de Student y el test U de Mann-Whitney para comparar variables cuantitativas y la prueba Chi-cuadrado para variables categóricas. Se consideró un nivel de significación de p<0,05. RESULTADOS: Se observaron 4.538 fármacos. Tras realizar la intervención, se redujeron un 49% los errores detectados durante el circuito farmacoterapéutico global (12,06% vs 6,15%; p<0,001). Además, se redujo un 91,6% (4,27% vs 0,36%; p=0,004) los errores en la etapa de almacenaje y un 75,8% (22,52% vs 5,46%; p<0,001) en la etapa de preparación/administración. Sin embargo, hubo un aumento en la etapa de dispensación (4,51% vs 15,29%; p<0,001). El rendimiento global se incrementó un 6% (87,9% vs 93,9%), el nivel de sigma aumentó de 2,67 a 3,04 y se redujeron un 49% de defectos por millón de oportunidades de error en la medicación. CONCLUSIONES: La implantación de Sistemas Automatizados de Dispensación con metodología Lean Seis Sigma ayuda a la creación de un entorno más seguro para el paciente, disminuyendo los errores de medicación en las etapas de almacenaje y preparación/administración, además de mejorar el rendimiento global del circuito.

Lean Seis Sigma en la implantación de sistemas automatizados de dispensación: mejora del uso seguro del medicamento en cirugía torácica / Lean Six Sigma in the implementation of automated dispensing systems: improving the safe use of medications in thoracic surgery

Fundamentos: Los errores de medicación son un problema importante que pueden provocar un daño en los pacientes hospitalizados. El objetivo principal del estudio fueevaluar los errores de medicación en el circuito farmacote rapéutico antes y después de realizar una intervención: implantación de un Sistema Automatizado de Dispensación conla utilización de metodología Lean Seis Sigma. El objetivosecundario fue evaluar el rendimiento del proceso, el nivelsigma y los defectos por millón de oportunidades de error enla medicación.Métodos: Estudio cuasi-experimental y aleatorizadorealizado en la Unidad de Cirugía Torácica de un HospitalEspañol. Un farmacéutico registró y evaluó los errores detectados durante las fases prentervención (julio-agosto 2017)y post-intervención (marzo-abril 2018). Las etapas analizadas fueron dispensación, almacenaje y preparación/administración. El farmacéutico observó un tercio de la medicacióndispensada, almacenada y preparada/administrada durante elperiodo de estudio. La medicación observada fue seleccionada de forma aleatoria utilizando el software AleatorMetod.xls.Para realizar el análisis estadístico se utilizó la prueba t deStudent y el test U de Mann-Whitney para comparar variablescuantitativas y la prueba Chi-cuadrado para variables categóricas. Se consideró un nivel de significación de p<0,05.Resultados: Se observaron 4.538 fármacos. Tras realizar la intervención, se redujeron un 49% los errores detectados durante el circuito farmacoterapéutico global (12,06%vs 6,15%; p<0,001). Además, se redujo un 91,6% (4,27% vs0,36%; p=0,004) los errores en la etapa de almacenaje y un75,8% (22,52% vs 5,46%; p<0,001) en la etapa de preparación/administración. Sin embargo, hubo un aumento en la etapa dedispensación (4,51% vs 15,29%; p<0,001).(AU)

Background: Medications errors are a major problemthat can cause a harm to inpatients. The main objective of thestudy was to compared medication errors in pharmacotherapeutic process before and after to carried out an intervention:to implant an automated dispensing cabine with to use LeanSix Sigma methodology. The secondary objective was to assess process performance, sigma level and defects per one million opportunities for medication error.Methods: Quasi-experimental and randomized studycarried out in a Thoracic Surgery Unit of a Spanish Hospital.A pharmaceutic recorded and assesed the medication errorsdetected during pre-intervention period (july-august 2017)and post-intervention period (march-april 2018). The stepsanalyzed were dispensing, storage and compounding/administration. The pharmacist observed a third of the medicationdispensed, stored and compounded/administered during thestudy period. The observed medication was randomly selected using AleatorMetod.xls software. To perform the statistical analysis, Student’s t test and Mann-Whitney U test wereused to compare quantitative variables, and Chi-square testfor qualitative variables. A significance level of p<0.05 wasconsidered.Results: The pharmaceutic recorded 4,538 drugs. Afterintervention, medication errors were decreased a 49% in totalpharmacotherapeutic process (12.06% vs 6.15%; p<0.001). Inaddition, errors were decreased a 91.6% (4.27% vs 0.36%;p=0.004) in the step of medication storage; and a 75.8%(22.52% vs 5.46%; p<0.001) in the step of drugs compounding/administration. However, medication errors were increased in the step of medication dispensing (4.51% vs 15.29%;p<0.001). The process performance increased a 6% (87.9%vs 93.9%), sigma level increased from 2.67 to 3.04 and defects per one million opportunities for medication error decreased a 49%.(AU)

Intervention by a clinical pharmacist carried out at discharge of elderly patients admitted to the internal medicine department: influence on readmissions and costs.

BACKGROUND: Patient education on pharmacological treatment could reduce readmissions. Our objective was to carry out a pharmacist intervention focused on providing information about high-risk medications to chronic patients and to analyse its influence on readmissions and costs. METHODS: A single-centre study with an intervention group and a retrospective control group was conducted. The intervention was carried out in all polymedicated patients ≥ 65 years who were admitted to internal medicine and signed the informed consent between June 2017 and February 2018. Patients discharged to nursing homes or long-term hospitals were excluded. The control group were all the patients who were admitted during the same months of 2014 who met the same inclusion criteria. The patients were classified according to the HOSPITAL score as having a low, intermediate, or high risk of potentially avoidable readmission. Outcome measures were 30-day readmission and cost data. To analyse the effect of the intervention on readmission, a logistic regression was performed. RESULTS: The study included 589 patients (286 intervention group; 303 control group). The readmission rate decreased from 20.13% to 16.43% in the intervention group [OR = 0.760 95% CI (0.495-1.166); p = 0.209)]. The incremental cost for the intervention to prevent one readmission was €3,091.19, and the net cost saving was €1,301.26. In the intermediate- and high-risk groups, readmissions were reduced 10.91% and 10.00%, and the net cost savings were €3,3143.15 and €3,248.71, respectively. CONCLUSIONS: The pharmacist intervention achieved savings in the number of readmissions, and the net cost savings were greater in patients with intermediate and high risks of potentially avoidable readmission according to the HOSPITAL score.

Rivaroxabán e inhibidores selectivosde la recaptación de serotonina: Análisis comparativo del riesgo de sangrado / Rivaroxaban and selective serotonin reuptake inhibitors: Bleeding risk resulting from their concomitant use

Objetivo: La combinación de rivaroxabán e inhibidores selectivos de larecaptación de serotonina presenta un riesgo de interacción farmacodinámicay farmacocinética que depende del tipo de inhibidor selectivo dela recaptación de serotonina empleado, ya que algunos son inhibidoresdel citocromo p450, mientras que otros no lo son. El objetivo del presenteestudio fue evaluar con datos de vida real si el tipo de inhibidor selectivode la recaptación de serotonina utilizado influye en la frecuencia y en lagravedad de sangrado en pacientes anticoagulados con rivaroxabán.Método: Estudio observacional, longitudinal, retrospectivo y unicéntrico,realizado entre enero de 2016 y febrero de 2020 en pacientes ≥ 18 añosque recibían rivaroxabán, en indicaciones autorizadas y financiadas, y queestaban siendo tratados concomitantemente con inhibidores selectivos dela recaptación de serotonina. Se establecieron dos cohortes en funcióndel inhibidor selectivo de la recaptación de serotonina coadministrado:inhibidores del CYP3A4 (grupo 1) —sertralina, fluoxetina y paroxetina—,y no inhibidores del CYP3A4 (grupo 2) —citalopram y escitalopram—. Seanalizaron los eventos hemorrágicos, la gravedad del sangrado, la dosisdiaria de rivaroxabán y la medicación concomitante que pudiese influir enel riesgo de sangrado.Resultados: Se incluyeron 146 pacientes (89 en el grupo 1 y 57 en elgrupo 2) y se identificaron un total de 35 eventos hemorrágicos (24% delos pacientes), de los que 12 fueron eventos mayores y 23 menores. Lafrecuencia de sangrado fue ligeramente mayor en el grupo 1 que en el 2(25,8% versus 21%), pero no se encontraron diferencias significativas entre ambos grupos, ni tampoco en la frecuencia de sangrados mayores (10,1%versus 5,3%; p = 0,235) o menores (13,5% versus 15,8%; p = 0,496).

Objective: The combination of selective serotonin reuptake inhibitorswith rivaroxaban may result in a dual interaction (pharmacokinetic andpharmacodynamic) depending on the type of selective serotonin reuptakeinhibitor employed (CYP3A4-inhibiting vs. non-CYP3A4 inhibiting). Thepurpose of this study was to use real world data to determine if the typeof selective serotonin reuptake inhibitor used plays a role in the risk andseverity of bleeding in patients receiving rivaroxaban.Method: This was a single-center retrospective longitudinal observationalstudy carried out between January 2016 and February 2020 inpatients aged 18 years or older treated concurrently with rivaroxaban(prescribed for treatments) and a selective serotonin reuptake inhibitor. Patients were divided into two groups according to the selective serotoninreuptake inhibitor they received, i.e., a CYP3A4 inhibitor (group 1): sertraline,fluoxetine and paroxetine, or a non-CYP3A4 inhibitor (group 2):citalopram and escitalopram. We analyzed the bleeding events and severity,the daily dose of rivaroxaban used and the medication administeredconcomitantly.Results: A total of 146 patients were included (89 in group 1 and 57in group 2) and 35 bleeding events (24% of patients) were identified, of which 12 were major and 23 were minor. The bleeding rate was higherin group 1 (25.8% vs 21.0%) but there were no differences in major bleeding(10.1% vs 5.3%; p = 0.235) or minor bleeding (13.5% vs 15.8%;p = 0.496).

Effectiveness, safety and cost analysis of dalbavancin in clinical practice.

OBJECTIVES: Dalbavancin is approved for the treatment of complicated skin and soft tissue infections. However, there is growing evidence that other gram-positive infections could be treated with this antibiotic. A study was undertaken in a tertiary hospital in Spain to evaluate the effectiveness and safety of dalbavancin in off-label indications and the potential healthcare cost savings. METHODS: A retrospective observational study including all patients treated with dalbavancin in our hospital from October 2016 to August 2019 was carried out. Demographic, clinical and safety variables were collected. Effectiveness was assessed using the clinical and microbiological resolution of the infection and the absence of hospital admissions due to the same infection in the following 3 months. RESULTS: A total of 102 patients were included (69.9% men, n=71; median age 72.5 years (range 56.0-84.0)). Treatment was off label in 71 cases (69.6%). The most frequent off-label indications were catheter-related bacteraemia (15.7%, n=16) and endocarditis (13.6%, n=14). All patients had previously received antibiotics. The main reason for switching to dalbavancin was patient discharge (79.4%, n=81). Dalbavancin was administered during hospitalisation in 66.7% of the patients and in the outpatient setting in 13.7%. The median reduction in length of hospital stay was 14 days per patient. A saving of about 4550 Euros per patient was estimated. 89 patients (93.7%) had clinical and microbiological resolution of the infection at the end of the study. One patient did not finish the dalbavancin infusion due to an allergic reaction. CONCLUSIONS: Our results suggest that dalbavancin is a safe and effective alternative to the off-label treatment of gram-positive infections. Its dosage facilitates early discharge and outpatient management of these patients.

Interacción entre ácido valproico con meropenemo ertapenem en pacientes con epilepsia: relevancia clínica y resultados de la intervención farmacéutica / Interaction between valproic acid and meropenem or ertapenem in patients with epilepsy: clinical relevance and results from pharmaceutical intervention

Objetivo: La interacción entre ácido valproico y carbapenems está descrita en la literatura y conlleva una disminución de los niveles plasmáticosde ácido valproico. Los objetivos son evaluar su relevancia en la prácticaclínica, conocer las variables que se asocian a un incremento de crisisepilépticas y analizar el impacto de la intervención farmacéutica paraevitar las consecuencias de dicha interacción.Método: En este estudio observacional retrospectivo se estudiaronpacientes con epilepsia hospitalizados entre 2016 y 2020. Se registróel tratamiento farmacológico prescrito en el ingreso y se revisó la presencia de otras interacciones que redujeran la concentración plasmática deácido valproico. La frecuencia de crisis epilépticas durante el año previo alingreso se comparó con la correspondiente al periodo de interacción. Serealizó una intervención en todos los episodios con la interacción detectada informando al prescriptor sobre la interacción y proponiendo sustitución de la antibioterapia, así como monitorización farmacocinética deácido valproico.Resultados: Se incluyeron 37 episodios. El 58,1% eran varones y lamediana de edad fue de 70 años. El 56,8% de los pacientes recibiómeropenem y el 43,2% restante, ertapenem. Para la duración del tratamiento concomitante entre ácido valproico y el carbapenem prescrito se obtuvo una mediana de 4 días. Se halló una razón de tasas de incidencia de 2,60 (intervalo de confianza del 95%: 1,61-4,21), por lo queesta interacción se asocia a una mayor frecuencia de crisis epilépticas.Se asoció una mayor frecuencia de crisis estadísticamente significativaen los pacientes tratados con más de un fármaco antiepiléptico. Los farmacéuticos hospitalarios detectaron 24 episodios (64,9%). (AU)

Objective: The literature has described the interaction between valproicacid and carbapenems. This interaction leads to decreases in plasmaconcentrations of valproic acid. The main objectives of this study were toassess its relevance in clinical practice, to identify variables associatedwith increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction.Method: An observational retrospective study of inpatients withepilepsy admitted between 2016 and 2020. Their pharmacologicaltreatment throughout admission was recorded, and the presence of otherinteractions leading to decreased plasma concentrations of valproicacid was reviewed. The seizure rate during the year prior to admissionwas compared to that during the interaction period. For every episodein which the interaction was detected, an intervention was conducted byproviding the prescriber with information on the interaction and suggesting a change of antibiotherapy as well as the pharmacokinetic monitoring of valproic acid.Results: 37 episodes were included. 58.1% of the patients were maleand median age was 70 years. In total, 56.8% of the patients receivedmeropenem and 43.2% received ertapenem. The median duration of concomitant treatment with valproic acid and carbapenem was 4 days. The incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus,this interaction was associated with a higher seizure rate. A statistically significant association was found between higher seizure rates andpatients treated with more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes (64.9%). In total, 17 interventions (70.8%)were accepted and 13 combinations were discontinued. Pharmacokineticmonitoring was conducted in 13 episodes (35.1%) and infratherapeuticlevels were found in all of them. (AU)

[Controlled supply of tocilizumab during the COVID-19 pandemic and its influence on the treatment of rheumatological patients.] / Suministro controlado de tocilizumab durante la pandemia de COVID-19 e influencia sobre el tratamiento de pacientes reumatológicos.

OBJECTIVE: Intravenous (IV) tocilizumab has been used to stop the inflammatory phase of SARS-CoV-2 infection. To preserve the largest number of IV units for this use, the Spanish Agency for Medicines and Health Products (AEMPS) carried out a controlled supply of it and recommended the change to a subcutaneous presentation (SC) of tocilizumab or sarilumab in all those patients in IV tocilizumab treatment for rheumatologic indications. The objective of this study was to evaluate the change from IV tocilizumab to SC presentation due to its controlled supply during the COVID-19 pandemic. METHODS: Retrospective observational study of adult patients (>18 years old) under treatment with IV tocilizumab follow-up by the Rheumatology Service of the Hospital 12 de Octubre. The follow-up period was 3 months (March 2020-June 2020) and 39 patients were included in the study. Variables related to the patients and their treatment were collected. A descriptive analysis of the data was carried out. RESULTS: In 69.23% (n=27) of the patients, treatment was changed to SC tocilizumab (n=23) or sarilumab (n=4). 44% of patients (n=12) switched back to their original IV tocilizumab treatment. The reasons for stopping treatment with SC tocilizumab were: drug intolerance (n=4), disease worsening (n=4), and patient preference (n=1). Regarding sarilumab, the reasons were drug intolerance (n=2) and patient preference (n=1). CONCLUSIONS: Almost half of the patients had to return to the original treatment. The main reason was intolerance to the new treatment, followed by ineffectiveness and patient preferences.

OBJETIVO: El tocilizumab intravenoso (IV) ha sido empleado para frenar la fase inflamatoria de la infección por SARS-CoV-2. Para reservar el mayor número de unidades IV para este uso, la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) realizó una distribución controlada del mismo y recomendó el cambio a una presentación subcutánea (SC), fuera tocilizumab o sarilumab, en todos aquellos pacientes en tratamiento con tocilizumab IV para indicaciones reumatológicas. El objetivo de este trabajo fue evaluar el cambio de tocilizumab IV a una presentación SC debido a su suministro controlado durante la pandemia de COVID-19. METODOS: Se realizó un estudio observacional retrospectivo de pacientes adultos (mayores de 18 años) en tratamiento con tocilizumab IV en seguimiento por el Servicio de Reumatología del Hospital 12 de octubre (Madrid). El periodo de seguimiento fue de tres meses (marzo 2020-junio 2020) y se incluyeron 39 pacientes en el estudio. Se recogieron variables relacionadas con el paciente y su tratamiento. Se realizó un análisis descriptivo de los datos. RESULTADOS: En el 69,23% (n=27) de los pacientes se cambió el tratamiento a tocilizumab SC (n=23) o sarilumab (n=4). El 44% (n=12) de los pacientes volvieron a cambiar a su tratamiento original con tocilizumab IV. Los motivos de interrupción de tratamiento con tocilizumab SC fueron: intolerancia al fármaco (n=4), empeoramiento de la enfermedad (n=4) y preferencia del paciente (n=1). Respecto al sarilumab, los motivos fueron intolerancia al fármaco (n=2) y preferencia del paciente (n=1). CONCLUSIONES: Casi la mitad de los pacientes tuvieron que volver al tratamiento original. El principal motivo fue intolerancia al nuevo tratamiento, seguido de ineficacia y preferencias del paciente.

Impact of a Pharmaceutical Care Program at Discharge on Patients at High Risk of Readmission According to the Hospital Score.

Background: A significant percentage of hospital readmissions within 30 days of discharge are a result of avoidable drug-related problems. Stratifying patients according to readmission risk is key to pharmaceutical intervention (PI) design strategies to improve treatment outcomes. Objective: To assess whether a pharmaceutical care (PC) program at discharge in polymedicated patients at high potentially avoidable readmission (PAR) risk, according to the HOSPITAL score, improves 30-day readmission rate (30-dRR). Methods: This prospective controlled, quasi-experimental, 11-month study included 163 chronic polymedicated patients (>5 medications) at high PAR risk according to the HOSPITAL score. We calculated the 30-dRR and number of medication variations and Medication Regimen Complexity Index-E (MRCI-E) after PI. Results were compared with a retrospective cohort of chronic patients at high PAR risk. Results: The 30-dRR was 18.4% in the intervention group and 25.6% in the control group (odds ratio [OR] = 0.66; 95% CI = 0.38 to 1.14). Total medication reduction (-1.28; 95% CI = -1.88 to -0.68), number of high-risk medications in chronic patients (-0.58; 95% CI = -0.9 to -0.26), and MRCI-E (-6.42; 95% CI = -8.07 to -4.76) were statistically significant (P < .001). The number of medications at discharge was associated with an increased readmission risk (OR = 1.07; 95% CI = 1.01 to 1.14). Conclusions: The degree of polypharmacy and patients' treatment complexity after hospital discharge significantly reduced as a result of the PC program compared with the control group. This highlights the need for patient selection and prioritization strategies for implementing PIs focused on reducing polypharmacy and preventing drug-related problems that may cause PAR.

Interaction between valproic acid and meropenem or ertapenem in patients with epilepsy: clinical relevance and results from pharmaceutical intervention.

OBJECTIVE: The literature has described the interaction between valproic acid  and carbapenems. This interaction leads to decreases in plasma concentrations  of valproic acid. The main objectives of this study were  to assess its relevance in clinical practice, to identify variables associated with  increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction. METHOD: An observational retrospective study of inpatients with epilepsy  admitted between 2016 and 2020. Their pharmacological treatment throughout  admission was recorded, and the presence of other interactions  leading to decreased plasma concentrations of valproic acid was reviewed. The  seizure rate during the year prior to admission was compared to that during  the interaction period. For every episode in which the interaction was detected, an intervention was conducted by providing the prescriber with information on  the interaction and suggesting a change of antibiotherapy as well as the  pharmacokinetic monitoring of valproic acid. RESULTS: 37 episodes were included. 58.1% of the patients were male and  median age was 70 years. In total, 56.8% of the patients received meropenem  and 43.2% received ertapenem. The median duration of  concomitant treatment with valproic acid and carbapenem was 4 days. The  incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus, this  interaction was associated with a higher seizure rate. A statistically significant  association was found between higher seizure rates and patients treated with  more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes  (64.9%). In total, 17 interventions (70.8%) were accepted and 13  combinations were discontinued. Pharmacokinetic monitoring was conducted in  13 episodes (35.1%) and infratherapeutic levels were found in all of them. CONCLUSIONS: The interaction between valproic acid and meropenem or ertapenem is clinically relevant. It is recommended that this combination should be avoided provided that a viable alternative is available.  Pharmaceutical intervention may contribute to preventing seizures associated with this combination.

Objetivo: La interacción entre ácido valproico y carbapenems está descrita en  la literatura y conlleva una disminución de los niveles plasmáticos de ácido  valproico. Los objetivos son evaluar su relevancia en la práctica clínica, conocer  las variables que se asocian a un incremento de crisis epilépticas y  analizar el impacto de la intervención farmacéutica para evitar las  consecuencias de dicha interacción.Método: En este estudio observacional retrospectivo se estudiaron pacientes  con epilepsia hospitalizados entre 2016 y 2020. Se registró el tratamiento  farmacológico prescrito en el ingreso y se revisó la presencia de otras  interacciones que redujeran la concentración plasmática de ácido valproico. La  frecuencia de crisis epilépticas durante el año previo al ingreso se comparó con  la correspondiente al periodo de interacción. Se realizó una intervención  en todos los episodios con la interacción detectada informando al prescriptor  sobre la interacción y proponiendo sustitución de la antibioterapia, así como  monitorización farmacocinética de ácido valproico.Resultados: Se incluyeron 37 episodios. El 58,1% eran varones y la mediana  de edad fue de 70 años. El 56,8% de los pacientes recibió meropenem y el  43,2% restante, ertapenem. Para la duración del tratamiento concomitante  entre ácido valproico y el carbapenem prescrito  se obtuvo una mediana de 4  días. Se halló una razón de tasas de incidencia de 2,60 (intervalo de confianza  del 95%: 1,61-4,21), por lo que esta interacción se asocia a una mayor  frecuencia de crisis epilépticas. Se asoció una mayor frecuencia de crisis  estadísticamente significativa en los pacientes tratados con más de un fármaco  antiepiléptico. Los farmacéuticos hospitalarios detectaron 24  episodios (64,9%). Se aceptaron 17 intervenciones farmacéuticas (70,8%) y  se suprimieron 13 combinaciones. Se realizó monitorización farmacocinética en  13 episodios (35,1%) y en todos se hallaron niveles infraterapéuticos. Conclusiones: La interacción entre ácido valproico y meropenem o ertapenem  es clínicamente relevante y se recomienda evitarla siempre que  existan alternativas viables. La intervención farmacéutica puede contribuir a  prevenir las crisis epilépticas favorecidas por esta combinación.

Paediatric viral myocarditis successfully treated with interferon beta-1b and corticoids.

WHAT IS KNOWN AND OBJECTIVE: In paediatrics, evidence regarding the treatment of viral myocarditis using interferon beta-1B is restricted to four children older than two years and there are no reported cases of infants. The objective was to describe the efficacy and safety of interferon beta-1B in two infants under one year of age with viral myocarditis. CASE SUMMARY: Two infants were admitted to the hospital presenting with respiratory symptoms. Echocardiogram showed myocardial damage. Parvovirus-B19 was detected using a PCR assay, and treatment with interferon beta-1B was initiated. Six months later, the cardiac function had recovered in both cases. WHAT IS NEW AND CONCLUSION: This is the first published series of cases of infants less than 1 year of age with viral myocarditis treated with interferon beta-1B.