Hypophysitis secondary to pembrolizumab: a case report and review of the literature.

Pembrolizumab is a mAb against the programmed cell death protein-1 (PD-1). It has been approved for the treatment of advanced melanoma (unresectable or metastatic) in adults. Side effects associated with the use of anti-PD-1 are usually considered well tolerated; nevertheless, there are immune-related adverse events that may require treatment discontinuation. A 79-year-old man diagnosed with stage IV right scapular melanoma experienced unspecific symptoms and alterations of the hypothalamus-hypophysis axis after six cycles with pembrolizumab. The case was compatible with immune-related hypophysitis. Autoimmune thyroiditis and primary hypophysitis were excluded and toxicity due to pembrolizumab was considered the cause of hypophysitis. Pembrolizumab was discontinued and toxicity was managed with corticosteroids and hormonal replacement therapy (HRT). After 7 months of follow-up, symptoms were controlled with HRT but thyrotropin and corticotropin hormones had not recovered. It was decided not to reintroduce immunotherapy. Although endocrine disorders are common with the use of anti-PD-1, hypophysitis is very rare. However, clinical signs and symptoms can be nonspecific, therefore, it has probably been underdiagnosed. Monitoring hormones before and during the treatment is important for an early diagnosis and also to replace the alterations with HRT to control the symptoms. Hormonal function does not always recover, but it does not mean immunotherapy cannot be restarted and it should be evaluated in every case.

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus / Efecto sobre la adherencia a medicaciones concomitantes tras el inicio del tratamiento con antivíricos de acción directa para el virus de la hepatitis C

INTRODUCTION: Many patients with hepatitis C virus (HCV) have associated comorbidities that require complex treatments. We sought to determine the impact of treatment with direct-acting antiviral agents (DAAs) for HCV on adherence to prescribed concomitant medications for associated comorbidities and to identify predictors of non-adherence to comedications. PATIENTS AND METHODS: HCV-infected patients treated with DAAs in a Spanish hospital between January 2015 and December 2016 and followed-up by the pharmacy unit were included in the study. Adherence to concomitant comedication prescribed before and during HCV therapy with DAAs was compared to adherence during the same number of weeks before DAA initiation. Demographic, clinical and pharmacotherapy variables were analyzed to determine factors associated with non-adherence. A multivariate regression model was created for prediction of non-adherence to concomitant medication. RESULTS: Data from 214 patients using prescribed concomitant therapies were analyzed. Significant reduction on adherence to comedications was observed after initiation of DAA treatment compared with a similar period before therapy initiation (29.9% vs. 36.9%, p = 0.032). The univariate analysis showed that polypharmacy and presence of vascular disease were associated negatively with adherence to concomitant medications (87.8%, p = 0.006 and 84.7%, p < 0.001, respectively). Multivariate analysis indicated that HIV/HBV coinfection was associated with adherence (OR 0.19; 95% CI 0.09-0.39), while polypharmacy was a predictor for non-adherence (OR 4.54; 95% CI 1.48-13.92). DISCUSSION: Adherence to concomitant medications decreases in HCV-infected patients when DAA therapy is initiated. Polypharmacy is a predictor for non-adherence, while HIV/HBV coinfection reduce non-adherence rates. Polymedicated patients on DAAs might benefit from close follow-up and educational programmes to improve their adherence

INTRODUCCIÓN: Muchos pacientes con virus de la hepatitis C (VHC) presentan comorbilidades que requieren tratamientos complejos. Queremos determinar el impacto del tratamiento con antivirales de acción directa (AAD) para el VHC en la adherencia a medicaciones concomitantes e identificar factores predictivos de no adherencia a comedicaciones. PACIENTES Y MÉTODOS: Pacientes tratados con AAD entre 2015 y 2016 se incluyeron en el estudio y se comparó su adherencia a medicaciones concomitantes antes y durante la terapia con AAD en un periodo de tiempo similar. Múltiples variables fueron analizadas para identificar factores asociados a la no-adherencia. Se creó un modelo de regresión multivariable para predecir la no adherencia a medicaciones concomitantes. RESULTADOS: Se analizaron datos de 214 pacientes en tratamientos concomitantes. Tras iniciar la terapia con AAD, la adherencia a las comedicaciones disminuyó respecto a la adherencia en ausencia de AAD (29,9% respecto al 36,9%; p = 0,032). El análisis univariante demostró que la polifarmacia y la enfermedad vascular estaban asociadas negativamente con la adherencia a las medicaciones concomitantes (87,8%, p = 0,006 y 84,7%, p < 0,001, respectivamente). El análisis multivariante indicó que la coinfección con VIH/VHB estaba asociada con la adherencia (OR: 0,19; IC 95%: 0,09-0,39), mientras que la polifarmacia era un predictor de no adherencia (OR: 4,54; IC 95%: 1,48-13,92). DISCUSIÓN: El inicio del tratamiento con AAD disminuye la adherencia a la comedicación en pacientes con VHC. La polifarmacia es predictor de no adherencia mientras que la coinfección con VIH/VHB la reduce. Aquellos pacientes polimedicados y en tratamiento con AAD podrían beneficiarse de un seguimiento estrecho para aumentar su adherencia

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus.

INTRODUCTION: Many patients with hepatitis C virus (HCV) have associated comorbidities that require complex treatments. We sought to determine the impact of treatment with direct-acting antiviral agents (DAAs) for HCV on adherence to prescribed concomitant medications for associated comorbidities and to identify predictors of non-adherence to comedications. PATIENTS AND METHODS: HCV-infected patients treated with DAAs in a Spanish hospital between January 2015 and December 2016 and followed-up by the pharmacy unit were included in the study. Adherence to concomitant comedication prescribed before and during HCV therapy with DAAs was compared to adherence during the same number of weeks before DAA initiation. Demographic, clinical and pharmacotherapy variables were analyzed to determine factors associated with non-adherence. A multivariate regression model was created for prediction of non-adherence to concomitant medication. RESULTS: Data from 214 patients using prescribed concomitant therapies were analyzed. Significant reduction on adherence to comedications was observed after initiation of DAA treatment compared with a similar period before therapy initiation (29.9% vs. 36.9%, p=0.032). The univariate analysis showed that polypharmacy and presence of vascular disease were associated negatively with adherence to concomitant medications (87.8%, p=0.006 and 84.7%, p<0.001, respectively). Multivariate analysis indicated that HIV/HBV coinfection was associated with adherence (OR 0.19; 95% CI 0.09-0.39), while polypharmacy was a predictor for non-adherence (OR 4.54; 95% CI 1.48-13.92). DISCUSSION: Adherence to concomitant medications decreases in HCV-infected patients when DAA therapy is initiated. Polypharmacy is a predictor for non-adherence, while HIV/HBV coinfection reduce non-adherence rates. Polymedicated patients on DAAs might benefit from close follow-up and educational programmes to improve their adherence.

Daño hepático inducido por dronedarona. Descripción de un caso clínico / Dronedarone-induced liver injury. A case report

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Adequancy of treatment with canaglifozin alter alerts pharmacovigilance in the health management área / Adecuación del tratamiento con canaglifozina tras alerta de farmacovigilancia en un área de gestión sanitaria

Objective: To analyze the impact of a strategy on the suitability of canaglizozin, and its level of acceptance, after issuing recommendations based on drug surveillance alerts issued by the Spanish Medicines and Medical Devices Agency (AEMPS). Method: A prospective intervention from may 2016 to october 2016. Location: South Seville Health Management Area. Participants: Patients with active canagliflozin prescription. Interventions: The study was conducted in three phases, the first one linked to the issuance of the safety information note on the canaglifozin by the AEMPS, the obtaining of the patient lists and the recommendations of the adequacy in the sending of letters. A second phase where the medical professional performed the actions and a final phase in which the degree of acceptance of the recommendations made by the Pharmacy Service is evaluated. Main measurements: Suitability of canaglizozin treatment and the level of acceptance by physicians. Results: A total of 61 patients at baseline were included in treatment canagliflozin. Of the total number of patients referred to, some type of intervention was performed by the family and community medicine doctor after the pharmaceutical intervention (PI), by means of letters (n = 30), 56.7% were monitored, 33.3% were discontinued and 10.0% were closely monitored Conclusions: Interventions aimed at reviewing patients on canagliptin, based on pharmacovigilance alerts, have been effective, with a high degree of acceptance by the family and community medicine practitioner (AU)

Objetivo: Analizar el impacto de una estrategia de adecuación de canaglifozina tras la emisión de recomendaciones en base a las notas de farmacovigilancia emitidas por la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), así como el grado de aceptación. Método: Estudio prospectivo de intervención desde mayo de 2016 a octubre de 2016. Emplazamiento: Área de Gestión Sanitaria Sur de Sevilla. Participantes: Pacientes con prescripción activa de canaglifozina. Intervenciones: Se realizó en tres fases: la primera ligada a la emisión de una nota informativa de seguridad sobre canaglifozina por la AEMPS, la obtención de listados de pacientes y las recomendaciones de adecuación mediante cartas, una segunda fase en la que el médico realizaba las actuaciones y una última fase en la cual se evalúo el grado de aceptación de las recomendaciones. Variables principales: Adecuación del tratamiento con canaglifozina y grado de aceptación de las recomendaciones por los facultativos médicos. Resultados: Se incluyeron un total de 61 pacientes en nuestro estudio en tratamiento con canaglifozina. Del total de los pacientes a los que se les realizó algún tipo de intervención por el médico de atención primaria tras la intervención farmacéutica (IF), realizada mediante el envío de cartas (n=30), al 56,7% se les monitorizó, al 33,3% se le suspendió el tratamiento y al 10,0% se les vigiló estrechamente. Conclusiones: Las intervenciones dirigidas a la revisión de pacientes en tratamiento con canaglizozin, en base a las alertas de farmacovigilancia, han sido efectivas, con un alto grado de aceptación por el especialista en medicina familiar y comunitaria (AU)

Adequancy of treatment with canaglifozin alter alerts pharmacovigilance in the health management area.

OBJECTIVE: To analyze the impact of a strategy on the suitability of canaglizozin, and its level of acceptance, after issuing recommendations based on drug surveillance alerts issued by the Spanish Medicines and Medical Devices Agency (AEMPS). DESIGN: A prospective intervention from may 2016 to october 2016. Location: South Seville Health Management Area. Participants: Patients with active canagliflozin prescription. Interventions: The study was conducted in three phases, the first one linked to the issuance of the safety information note on the canaglifozin by the AEMPS, the obtaining of the patient lists and the recommendations of the adequacy in the sending of letters. A second phase where the medical professional performed the actions and a final phase in which the degree of acceptance of the recommendations made by the Pharmacy Service is evaluated. MAIN MEASUREMENTS: Suitability of canaglizozin treatment and the level of acceptance by physicians. RESULTS: A total of 61 patients at baseline were included in treatment canagliflozin. Of the total number of patients referred to, some type of intervention was performed by the family and community medicine doctor after the pharmaceutical intervention (PI), by means of letters (n = 30), 56.7% were monitored, 33.3% were discontinued and 10.0% were closely monitoredConclusions: Interventions aimed at reviewing patients on canagliptin, based on pharmacovigilance alerts, have been effective, with a high degree of acceptance by the family and community medicine practitioner.

Objetivo: Analizar el impacto de una estrategia de adecuación de canaglifozina tras la emisión de recomendaciones en base a las notas de farmacovigilancia emitidas por la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), así como el grado de aceptación.Diseño: Estudio prospectivo de intervención desde mayo de 2016 a octubre de 2016.Emplazamiento: Área de Gestión Sanitaria Sur de Sevilla. Participantes: Pacientes con prescripción activa de canaglifozina. Intervenciones: Se realizó en tres fases: la primera ligada a la emisión de una nota informativa de seguridad sobre canaglifozina por la AEMPS, la obtención de listados de pacientes y las recomendaciones de adecuación mediante cartas, una segunda fase en la que el médico realizaba las actuaciones y una última fase en la cual se evalúo el grado de aceptación de las recomendaciones.Variables principales: Adecuación del tratamiento con canaglifozina y grado de aceptación de las recomendaciones por los facultativos médicos.Resultados: Se incluyeron un total de 61 pacientes en nuestro estudio en tratamiento con canaglifozina. Del total de los pacientes a los que se les realizó algún tipo de intervención por el médico de atención primaria tras la intervención farmacéutica (IF), realizada mediante el envío de cartas (n=30), al 56,7% se les monitorizó, al 33,3% se le suspendió el tratamiento y al 10,0% se les vigiló estrechamente.Conclusiones: Las intervenciones dirigidas a la revisión de pacientes en tratamiento con canaglizozin, en base a las alertas de farmacovigilancia, han sido efectivas, con un alto grado de aceptación por el especialista en medicina familiar y comunitaria.

Prevalence of drug interactions in elderly patients with multimorbidity in primary care.

Background Drug interactions (DIs) are a significant cause of medication-related problems. The aging population, high chronic diseases prevalence and polypharmacy are closely associated factors. Aim of the review To study the prevalence, types and associated factors of DIs in multimorbidity patients of over 65 years of age in primary care. Methods Relevant studies on DI prevalence in this population were reviewed in PubMed, Cochrane Library and EMBASE (January 2000-December 2015). Independent variables (duration, target population, age, sex, mean of drugs and diseases, geographical localization, DI databases used and study designs) and dependent variables (prevalence, number of DIs per 100 patients and per patient, number of clinically-relevant DIs per 100 patients, most common DI and associated factors) were classified for each article. Results The search generated 749 articles and 46 duplicates were discarded. After reviewing, 10 articles were included. Seven studies were observational and 3 were quasi-experimental. Seven out of 10 used interaction databases. Only 2 studies described both actual and potential DIs. The prevalence of multimorbidity patients with DI ranged from 25.1 to 100% and the number of DIs per 100 patients was from 30 to 388.3. All the lower values correspond to the study conducted at the nursing home. This could be due to special care offered in these centres, where the medication is more controlled. The most frequent DIs were reported in five articles. However, these results could not be correlated since they were ranked using different methodologies. ACEIs, diuretics and NSAID were the most common therapeutic groups. Finally, 5 studies identified factors associated with the presence of potential DIs. The number of drugs and age were the most significant factors. Conclusions There is little evidence of prevalence of actual and potential DIs in elderly patients with multimorbidity in outpatient settings, showing widely heterogeneous results.

Suitability of teriparatide and level of acceptance of pharmacotherapeutic recommendations in a healthcare management area.

OBJECTIVE: To analyse the suitability of teriparatide prescriptions for osteoporosis treatment in a health management area, as well as the level of acceptance of pharmacotherapeutic recommendations made to physicians. DESIGN: A prospective interventional study conducted from february 2015 to june 2015. SETTING: South Seville Health Management Area. PARTICIPANTS: Patients receiving teriparatide. MAIN MEASUREMENTS: Suitability of teriparatide prescriptions according to Clinical Practice Guidelines and level of acceptance of pharmacotherapeutic recommendations. RESULTS: Teriparatide prescriptions were unsuitable in 45 patients (68.2%); 11 due to no indication, 17 patients did not have previous treatments with first-line drugs, 6 due to contraindications and 9 patients were treated for more than 24 months with the drug. Besides, 4 prescriptions were unsuitable because of combination with other therapies. The acceptance of pharmacotherapeutic recommendations was 64.4%, leading to teriparatide discontinuation in 21 patients (72.4%), and a switch to alendronate or ibandronate in another 8 patients. CONCLUSIONS: A high percentage of teriparatide prescriptions is unsuitable in our health care management area, but it has decreased after pharmacist intervention.

Objetivo: Analizar la adecuación de la prescripción de teriparatida en el tratamiento de la osteoporosis en un área de gestión sanitaria, así como el grado de aceptación por el médico de las recomendaciones de intervención realizadas. Diseño: Estudio prospectivo de intervención desde febrero de 2015 a junio de 2015. Emplazamiento: Área de Gestión Sanitaria Sur de Sevilla. Participantes: Pacientes con prescripción activa de teriparatida. Mediciones principales: Adecuación de la prescripción de teriparatida y grado de aceptación por el médico de las recomendaciones farmacoterapéuticas. Resultados: La prescripción de teriparatida fue inadecuada en 45 pacientes (68,2%). Once pacientes no cumplían los criterios de tratamiento, mientras que 17 no habían tenido prescrito previamente otro medicamento para la prevención de fracturas. Seis pacientes presentaban alguna contraindicación. En 9 pacientes la duración de la terapia fue superior a los 24 meses recomendados. Cuatro de ellas (dos ya inadecuadas) por combinación inadecuada con otros medicamentos. El grado de aceptación de las recomendaciones farmacoterapéuticas realizadas por farmacia fue del 64,4%, produciéndose en 21 pacientes (72,4%) la suspensión de teriparatida y en 8, el cambio a otro medicamento de primera línea: ibandrónico, en tres de ellos, y alendrónico, en el resto. Conclusiones: El número de pacientes con prescripciones inadecuadas de teriparatida es elevado en nuestra área, pero ha disminuido tras realizar intervenciones con recomendaciones farmacoterapéuticas de adecuación del tratamiento.

Suitability of teriparatide and level of acceptance of pharmacotherapeutic recommendations in a healthcare management área / Adecuación de la teriparatida y grado de aceptación de las recomendaciones farmacoterapéuticas en un área de gestión sanitaria

Objective: To analyse the suitability of teriparatide prescriptions for osteoporosis treatment in a health management area, as well as the level of acceptance of pharmacotherapeutic recommendations made to physicians. Design: A prospective interventional study conducted from february 2015 to june 2015. Setting: South Seville Health Management Area. Participants: Patients receiving teriparatide. Main measurements: Suitability of teriparatide prescriptions according to Clinical Practice Guidelines and level of acceptance of pharmacotherapeutic recommendations. Results: Teriparatide prescriptions were unsuitable in 45 patients (68.2%); 11 due to no indication, 17 patients did not have previous treatments with first-line drugs, 6 due to contraindications and 9 patients were treated for more than 24 months with the drug. Besides, 4 prescriptions were unsuitable because of combination with other therapies. The acceptance of pharmacotherapeutic recommendations was 64.4%, leading to teriparatide discontinuation in 21 patients (72.4%), and a switch to alendronate or ibandronate in another 8 patients. Conclusions: A high percentage of teriparatide prescriptions is unsuitable in our health care management area, but it has decreased after pharmacist intervention (AU)

Objetivo: Analizar la adecuación de la prescripción de teriparatida en el tratamiento de la osteoporosis en un área de gestión sanitaria, así como el grado de aceptación por el médico de las recomendaciones de intervención realizadas. Diseño: Estudio prospectivo de intervención desde febrero de 2015 a junio de 2015. Emplazamiento: Área de Gestión Sanitaria Sur de Sevilla. Participantes: Pacientes con prescripción activa de teriparatida. Mediciones principales: Adecuación de la prescripción de teriparatida y grado de aceptación por el médico de las recomendaciones farmacoterapéuticas. Resultados: La prescripción de teriparatida fue inadecuada en 45 pacientes (68,2%). Once pacientes no cumplían los criterios de tratamiento, mientras que 17 no habían tenido prescrito previamente otro medicamento para la prevención de fracturas. Seis pacientes presentaban alguna contraindicación. En 9 pacientes la duración de la terapia fue superior a los 24 meses recomendados. Cuatro de ellas (dos ya inadecuadas) por combinación inadecuada con otros medicamentos. El grado de aceptación de las recomendaciones farmacoterapéuticas realizadas por farmacia fue del 64,4%, produciéndose en 21 pacientes (72,4%) la suspensión de teriparatida y en 8, el cambio a otro medicamento de primera línea: ibandrónico, en tres de ellos, y alendrónico, en el resto Conclusiones: El número de pacientes con prescripciones inadecuadas de teriparatida es elevado en nuestra área, pero ha disminuido tras realizar intervenciones con recomendaciones farmacoterapéuticas de adecuación del tratamiento (AU)