Análisis de las interacciones de nirmatrelvir/ritonavir en pacientes ambulatorios en atención primaria / Nirmatrelvir/ritonavir drug-drug interactions in primary care outpatients

Fundamento. Nirmatrelvir/ritonavir es un antiviral oral con un alto potencial de producir interacciones farmacológicas. La población candidata a recibirlo es mayoritariamente vulnerable, con enfermedades crónicas y polimedicada. El objetivo es evaluar la validación farmacéutica previa a la ad-ministración del antiviral.Material y métodos. Las interacciones farmacológicas entre nirmatrelvir/ritonavir y el tratamiento habitual se consulta-ron en fichas técnicas y las herramientas de interacciones de UpToDate® y Universidad de Liverpool®. Se incluyeron las prescripciones validadas por un farmacéutico de atención primaria (abril/2022-abril/2023). Resultados. Se incluyeron 159 pacientes; en 83 se detecta-ron 168 interacciones que podían suponer un cambio en su tratamiento. Las estatinas (25,6%), anticoagulantes (10,7%) y antihipertensivos (10,7%) fueron los grupos terapéuticos más frecuentemente implicados. La suspensión (53,0%) y reducción de dosis (22,6%) fueron los cambios de trata-miento más frecuentes. Conclusiones. La revisión de potenciales interacciones far-macológicas, los ajustes posológicos y las modificaciones del tratamiento habitual del paciente han evitado potenciales to-xicidades, mejorando la seguridad de nirmatrelvir/ritonavir (AU)

Background. The oral antiviral nirmatrelvir/ritonavir inter-acts with a range of drugs. Candidate patients to receive this antiviral agent are usually vulnerable, multipathological and polymedicated. The objective is to evaluate the phar-maceutical validation prior to the administration of the an-tiviral.Material and methods. Drug-drug interactions between nirmatrelvir/ritonavir and patients’ usual treatment medi-cations were checked in product information and in the Up-ToDate® and the University of Liverpool® interaction tools. We included validated prescriptions between April/2022 and April/2023 by a Primary Care pharmacist.Results. Of the 159 study patients, 168 interactions were found in 83 individuals, which may have led to changes of their usual treatment. Statins (25.6%), anticoagulants (10.7%), and antihypertensives (10.7%) were the most fre-quently implicated therapeutic groups. Discontinuation (53.0%) and dose reduction (22.6%) were the most common treatment changes. Conclusions. Our search of potential drug interactions and subsequent dose adjustments and modifications of the pa-tient’s usual treatment has helped avoid potential toxicities ensuring a safe use of nirmatrelvir/ritonavir (AU)

[Nirmatrelvir/ritonavir drug-drug interactions in primary care outpatients]. / Análisis de las interacciones de nirmatrelvir/ritonavir en pacientes ambulatorios en Atención primaria

BACKGROUND: The oral antiviral nirmatrelvir/ritonavir interacts with a range of drugs. Candidate patients to receive this antiviral agent are usually vulnerable, multipathological and polymedicated. The objective is to evaluate the pharmaceutical validation prior to the administration of the antiviral. MATERIAL AND METHODS: Drug-drug interactions between nirmatrelvir/ritonavir and patients' usual treatment medications were checked in product information and in the UpToDate® and the University of Liverpool® interaction tools. We included validated prescriptions between April/2022 and April/2023 by a Primary Care pharmacist. RESULTS: Of the 159 study patients, 168 interactions were found in 83 individuals, which may have led to changes of their usual treatment. Statins (25.6%), anticoagulants (10.7%), and antihypertensives (10.7%) were the most frequently implicated therapeutic groups. Discontinuation (53.0%) and dose reduction (22.6%) were the most common treatment changes. CONCLUSIONS: Our search of potential drug interactions and subsequent dose adjustments and modifications of the patient's usual treatment has helped avoid potential toxicities ensuring a safe use of nirmatrelvir/ritonavir.

Tratamiento de la COVID-19, ¿qué hemos aprendido? / COVID-19 treatment, what have we learned?

En diciembre de 2019 surgió un nuevo coronavirus, muy virulento y que provocaba un cuadrosevero a nivel respiratorio. La falta de experiencia con esta nueva enfermedad, unida a sugravedad y alta mortalidad, hizo que se utilizaran una gran cantidad de medicamentos sinexperiencia y se investigara sobre nuevas terapias específicas para combatirlo. Los primeros medicamentos que se utilizaron fueron antirretrovirales, usados habitualmente para eltratamiento del virus de la inmunodeficiencia humana, y antiparasitarios, por su actividadinmunosupresora. Además, debido a la neumonía que producía este nuevo virus se utilizabanantibióticos por el riesgo de sobreinfección bacteriana, además de corticoides. Posteriormente, se comenzaron a usar terapias inmunomoduladoras como interferones, anticuerposmonoclonales o moléculas pequeñas dirigidas contra dianas implicadas en el proceso de lainflamación. Durante todo este tiempo surgieron nuevas terapias como remdesivir, cuyaspautas de uso fueron cambiando a lo largo de los meses. En enero de 2022 cambió el paradigma de tratamiento de esta enfermedad, ya que se incluyeron nuevas alternativas tera-péuticas tanto para el tratamiento de esta enfermedad como para su prevención, como sonsotrovimab, casirivimab-imdevimab o nirmatrelvir/ritonavir. Desde este momento, la AgenciaEspañola del Medicamento y Productos Sanitarios publicó una serie de recomendaciones deutilización de estos nuevos medicamentos, que se han ido actualizando hasta la fecha. Eneste artículo hacemos una revisión de los tratamientos utilizados desde el inicio de la pandemia hasta enero de 2023.(AU)

[Off-label use of gabapentinoid drugs: is it necessary a deprescription strategy?] / Gabapentinoides en indicaciones no autorizadas en la ficha técnica: ¿es necesaria una estrategia de desprescripción?

OBJECTIVE: To evaluate gabapentin and pregabalin treatment adequacy to label indications, to analyze off-label use and to identify patients at high risk of respiratory depression. METHOD: An observational, retrospective study was performed. It included patients treated with pregabalin and gabapentin during 2020 in Navarre. RESULTS: A total of 9778 patients were treated with gabapentin or pregabalin during the first two months of 2020. In 56% of the cases, gabapentinoids were prescribed for off-label uses. Sixty percent of patients were taking at least one central nervous system (CNS) depressant drug concomitantly, 33% of them opioids, 20% of them combined opioids with CNS depressants and 4% of them at least one systemic antihistamine. In addition, 11% of the patients had a diagnosis of asthma or COPD. Prevalences remained constant along the year. CONCLUSIONS: It is necessary to implement a gabapentinoid deprescription strategy to improve its use and reduce safety problems.

Primary esophageal diffuse large B-cell lymphoma.

A 76-year-old man presented with dysphagia, epigastric pain and weight loss for the last two months. Heavy sweating was also presented. Past medical conditions included type 2 diabetes. He had no evidence of any immunosupressive disease including HIV infection. Physical examination only revealed low-grade fever. Laboratory data showed leukocytosis. Gastroscopy evidenced a complete esophageal stenosis starting at 30 cm, with a severely friable mucosa of malignant appearance. The results of biopsies were insufficient for diagnosis of malignancy. Computed tomography demonstrated a 10-cm irregular tumor located in the distal and middle thirds of the esophagus, which resulted in narrowing of the lumen. Involving tracheal carina, bronchus, and descending aorta were observed. Perforation signs were also seen. Distant metastases were not found. Empirical treatment with piperacillin/tazobactan was started. A surgical gastrostomy to allows nutritional support was performed. Two other gastroscopies were performed resulting in an inconclusive diagnosis. Finally, flow cytometry performed in samples obtained by endobronchial ultrasound-guided biopsy evidenced prominent clonal B-cell populations consistent with extranodal diffuse large B-cell lymphoma exhibing CD10 expression. A treatment with Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was started. Primary esophageal diffuse large B-cell lymphoma (DLBCL), a variant of non-Hodgkin's lymphoma, accounts for less than 1% of all cases of gastrointestinal lymphomas.

Gabapentinoides en indicaciones no autorizadas en la ficha técnica: ¿es necesaria una estrategia de desprescripción? / Off-label use of gabapentinoid drugs: is it necessary a deprescription strategy?

Objetivo: Evaluar la adecuación de los tratamientos con gabapentina y pregabalina a las indicaciones autorizadas, analizar su uso en las no autorizadas e identificar los pacientes con más riesgo de sufrir depresión respiratoria. Método: Estudio observacional retrospectivo que incluyó a los pacientes en tratamiento con gabapentina o pregabalina en 2020 en Navarra. Resultados: Se incluyeron 9778 pacientes en tratamiento con gabapentina o pregabalina durante el primer bimestre de 2020. En el 56% de los casos se prescribieron para indicaciones no autorizadas. El 60% tomaba concomitantemente al menos un depresor del sistema nervioso central (SNC), el 33% algún opiáceo, el 20% opiáceos combinados con depresores del SNC y el 4% algún antihistamínico. El 11% tenía diagnóstico de asma o enfermedad pulmonar obstructiva crónica. Estas prevalencias se mantuvieron constantes durante el resto del año. Conclusiones: Es necesario implementar una estrategia de desprescripción de gabapentinoides para adecuar su uso y disminuir los problemas de seguridad. (AU)

Objective: To evaluate gabapentin and pregabalin treatment adequacy to label indications, to analyze off-label use and to identify patients at high risk of respiratory depression. Method: An observational, retrospective study was performed. It included patients treated with pregabalin and gabapentin during 2020 in Navarre. Results: A total of 9778 patients were treated with gabapentin or pregabalin during the first two months of 2020. In 56% of the cases, gabapentinoids were prescribed for off-label uses. Sixty percent of patients were taking at least one central nervous system (CNS) depressant drug concomitantly, 33% of them opioids, 20% of them combined opioids with CNS depressants and 4% of them at least one systemic antihistamine. In addition, 11% of the patients had a diagnosis of asthma or COPD. Prevalences remained constant along the year. Conclusions: It is necessary to implement a gabapentinoid deprescription strategy to improve its use and reduce safety problems.

[Study protocol: A strategy for deprescribing statins and ezetimibe in primary prevention of cardiovascular disease in patients older than 75 years: health outcomes analysis.] / Protocolo del estudio Estrategia de deprescripción de estatinas y ezetimiba en prevención primaria en mayores de 75 años: análisis de los resultados en salud.

OBJECTIVE: The benefit-risk balance of statins and ezetimibe as primary prevention of cardiovascular disease is controversial in elderly patients due to the doubts about their effectiveness and certainty about adverse effects. The aim of this paper was to analyze health outcomes of a statin and ezetimibe deprescription strategy in patients aged 75 or older treated with these drugs for primary prevention of cardiovascular disease. METHODS: An observational ambispective cohort study was made to evaluate health outcomes after the implementation of a strategy for deprescribing statins and ezetimibe in patients aged 75 or older who take these drugs for primary prevention of cardiovascular disease. To avoid the risk of bias due to non-random assignment of patients to different groups, a propensity score will be calculated for each patient using logistic regression. The outcome of interest will be the deprescription or not of statins or ezetimibe. Time to hospital admission or death from any cause and other variables related to health outcomes will be analysed. Groups with and without statin or ezetimibe deprescription will be compared by survival analysis using Cox regression to estimate the hazard ratio. CONCLUSIONS: It is expected to obtain health outcomes of the strategy of deprescribing statins and ezetimibe in primary prevention in patients aged 75 or older. They will provide information on the advisability of continuing the strategy.

OBJETIVO: El balance beneficio-riesgo de estatinas y ezetimiba como prevención primaria de la enfermedad cardiovascular (ECV) resulta controvertido en pacientes de edad avanzada, debido a las dudas sobre su efectividad y las certezas sobre efectos adversos. El objetivo de este estudio fue analizar los resultados en salud de una estrategia de deprescripción de estatinas y ezetimiba en prevención primaria de ECV en pacientes mayores de 75 años. METODOS: Se realizó un estudio ambispectivo de cohortes para evaluar los resultados en salud obtenidos tras la implementación de una estrategia poblacional de deprescripción de estatinas y ezetimiba en pacientes con edad igual o mayor a 75 años que tomaban estos fármacos como prevención primaria de ECV. Para evitar posibles sesgos debidos a la asignación no aleatoria de los pacientes a los distintos grupos, se calculará un índice de propensión para cada paciente utilizando una regresión logística, en la que la variable de resultado será la deprescripción o no de estatinas o ezetimiba. Se analizará el tiempo hasta el ingreso hospitalario o la muerte por cualquier causa y otras variables relacionadas con resultados en salud. Se compararán los grupos con y sin deprescripción de estatina o ezetimiba mediante un análisis de supervivencia utilizando un modelo de riesgos proporcionales de Cox para estimar el hazard ratio. CONCLUSIONES: Se espera obtener información sobre los resultados en salud de la estrategia de deprescripción de estatinas y ezetimiba en prevención primaria en mayores de 75 años que informarán sobre la conveniencia de continuarla.

Protocolo del estudioEstrategia de deprescripción deestatinas y ezetimiba en prevenciónprimaria en mayores de 75 años: análisis de los resultados en salud / Study protocol: A strategy for deprescribing statins and ezetimibe in primary prevention of cardiovascular disease in patients older than 75 years: health outcomes analysis

FUNDAMENTOS: l balance beneficio-riesgo de estatinas y ezetimiba como prevención primaria de la enfermedad cardiovascular (ECV) resulta controvertido en pacientes de edad avanzada, debido a las dudas sobre su efectividad y las certezas sobre efectos adversos. El objetivo de este estudio fue analizar los resultados en salud de una estrategia de deprescripción de estatinas y ezetimiba en prevención primaria de ECV en pacientes mayores de 75 años. MÉTODOS: Se realizó un estudio ambispectivo de cohortes para evaluar los resultados en salud obtenidos tras la implementación de una estrategia poblacional de deprescripción de estatinas y ezetimiba en pacientes con edad igual o mayor a 75 años que tomaban estos fármacos como prevención primaria de ECV. Para evitar posibles sesgos debidos a la asignación no aleatoria de los pacientes a los distintos grupos, se calculará un índice de propensión para cada paciente utilizando una regresión logística, en la que la variable de resultado será la deprescripción o no de estatinas o ezetimiba. Se analizará el tiempo hasta el ingreso hospitalario o la muerte por cualquier causa y otras variables relacionadas con resultados en salud. Se compararán los grupos con y sin deprescripción de estatina o ezetimiba mediante un análisis de supervivencia utilizando un modelo de riesgos proporcionales de Cox para estimar el hazard ratio. CONCLUSIONES: Se espera obtener información sobre los resultados en salud de la estrategia de deprescripción de estatinas y ezetimiba en prevención primaria en mayores de 75 años que informarán sobre la conveniencia de continuarla.(AU)

BACKGROUND: The benefit-risk balance of statins and ezetimibe as primary prevention of cardiovascular disease is controversial in elderly patients due to the doubts about their effectiveness and certainty about adverse effects. The aim of this paper was to analyze health outcomes of a statin and ezetimibe deprescription strategy in patients aged 75 or older treated with these drugs for primary prevention of cardiovascular disease. METHODS: An observational ambispective cohort study was made to evaluate health outcomes after the implementation of a strategy for deprescribing statins and ezetimibe in patients aged 75 or older who take these drugs for primary prevention of cardiovascular disease. To avoid the risk of bias due to non-random assignment of patients to different groups, a propensity score will be calculated for each patient using logistic regression. The outcome of interest will be the deprescription or not of statins or ezetimibe. Time to hospital admission or death from any cause and other variables related to health outcomes will be analysed. Groups with and without statin or ezetimibe deprescription will be compared by survival analysis using Cox regression to estimate the hazard ratio. CONCLUSIONS: It is expected to obtain health outcomes of the strategy of deprescribing statins and ezetimibe in primary prevention in patients aged 75 or older. They will provide information on the advisability of continuing the strategy.(AU)

Improving access to care in low and middle-income countries: institutional factors related to enrollment and patient outcome in a cancer drug access program.

BACKGROUND: Limited access to drugs is a crucial barrier to reducing the growing impact of cancer in low- and middle-income countries. Approaches based on drug donations or adaptive pricing strategies yield promising but varying results across countries or programs, The Glivec International Patient Assistance Program (GIPAP) is a program designed to provide imatinib free of charge to patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST). The objective of this work was to identify institutional factors associated with enrollment and patient survival in GIPAP. METHODS: We analyzed follow-up data from 4,946 patients participating in 47 institutions within 44 countries between 2003 and 2010. Active status in the program was considered as a proxy for survival. RESULTS: Presence of ≥1 hematologist or oncologist at the institution was associated with increased patient enrollment. After adjusting for individual factors such as age (>55 years: Hazard Ratio [HR] = 1.42 [1.16; 1.73]; p = 0.001) and initial stage of disease (accelerated or blast crisis at diagnosis: HR = 4.16 [1.87; 9.25]; p < 10⁻4), increased survival was found in institutions with research capabilities (HR = 0.55 [0.35; 0.86]; p = 0.01) and those with enrollment of >5 patients/year into GIPAP (HR = 0.48 [0.35; 0.67]; p < 10⁻4), while a non-significant trend for decreased survival was found for treatment at a public institution (HR = 1.32 [0.95; 1.84]; p = 0.10). The negative impact of an accelerated form of CML was attenuated by the presence of ≥1 hematologist or oncologist at the institution (interaction term HR = 0.43 [0.18; 0.99]; p = 0.05). CONCLUSIONS: Application of these findings to the support and selection of institutions participating in GIPAP may help to optimize care and outcomes for CML and GIST patients in the developing world. These results may also be applicable to the treatment of patients with other forms of cancer, due to the overlap of infrastructure and staff resources used to treat a variety of cancer indications. A multi-sector approach is required to address these barriers.

Tuberculosis peritoneal por Mycobacterium bovis en paciente cirrótico / Peritoneal tuberculosis due to Mycobacterium bovis in a cirrhotic patient

La tuberculosis (TBC) peritoneal aislada es una forma de presentación extrapulmonar poco frecuente en los países industrializados. En la mayoría de los casos surge como resultado de la reactivación y la diseminación hematógena de una infección latente. Aunque la clínica y el análisis del líquido ascítico (predominio linfocítico, gradiente de albúmina entre suero y líquido ascítico inferior o igual a 1g/dl y concentración de adenosina deaminasa superior o igual a 39U/l) dan la sospecha diagnóstica, el diagnóstico de certeza es microbiológico. Por otro lado, Mycobacterium bovis es el causante de la TBC en animales, y su transmisión a humanos es poco frecuente en áreas desarrolladas, dado que suele ocurrir a través de la ingestión de leche contaminada no pasteurizada. Se presenta el caso de un paciente con cirrosis y ascitis causada por una infección muy poco común en España (AU)

Isolated peritoneal tuberculosis is an uncommon extrapulmonary form of presentation of tuberculosis in industrialized countries. In most cases, this disease is the result of reactivation and secondary hematogenous spread of a latent infection. Although the suspected diagnosis is given by clinical manifestations and analysis of ascitic fluid (lymphocytic predominance, albumin gradient between serum and ascitic fluid ⩽1g/dl and adenosine deaminase concentration ⩾39U/L), microbiologic assessment is required for the definitive diagnosis. Mycobacterium bovis causes tuberculosis in animals. Transmission to humans is rare in developed areas, given that it usually occurs through ingestion of unpasteurized contaminated milk. We present a patient with cirrhosis who developed ascites caused by an exceptional infection in our setting (AU)

[Peritoneal tuberculosis due to Mycobacterium bovis in a cirrhotic patient]. / Tuberculosis peritoneal por Mycobacterium bovis en paciente cirrótico.

Isolated peritoneal tuberculosis is an uncommon extrapulmonary form of presentation of tuberculosis in industrialized countries. In most cases, this disease is the result of reactivation and secondary hematogenous spread of a latent infection. Although the suspected diagnosis is given by clinical manifestations and analysis of ascitic fluid (lymphocytic predominance, albumin gradient between serum and ascitic fluid 1g/dl and adenosine deaminase concentration > or = 39 U/L), microbiologic assessment is required for the definitive diagnosis. Mycobacterium bovis causes tuberculosis in animals. Transmission to humans is rare in developed areas, given that it usually occurs through ingestion of unpasteurized contaminated milk. We present a patient with cirrhosis who developed ascites caused by an exceptional infection in our setting.