Potential drug-drug interactions in hospitalised haematological patients.

Background Frequently, haematological patients undergo highly complex and intensive treatment protocols, so a high risk of drug-drug interactions could be expected. Objectives To determine prevalence of clinically relevant drug-drug interactions, to identify the most frequent drug-drug interactions and associated risk factors. Methods A prospective, observational and descriptive study was carried out from November 2012 to February 2013. Twice a week, every patient's treatment sheet was collected. Each medication list was screened through two databases: Thomson MicromedexTM and Drug Interaction FactsTM. All identified potential drug-drug interactions with a moderate or higher severity rating were recorded. Summary statistics were used to describe patient and disease characteristics, most often prescribed drugs, and frequency, types and classification of drug-drug interactions. Multiple logistic regression models were used to identify risk factors associated with drug-drug interactions. Results A total of 2061 drug-drug interactions were detected in 317 treatment sheets from 58 patients. The prevalence of treatment sheets with drug-drug interactions by Micromedex and Drug Interaction Facts databases were 74.1% and 56.8%, respectively. Azole antifungals, immunosuppressive drugs, antiemetics, antidepressants, acid suppressants and corticosteroids were the most frequent involved drugs. In multivariate analysis, the main risk factor associated with increased odds for drug-drug interactions was a higher number of non-antineoplastic drugs. Conclusions The prevalence of drug-drug interactions was common, with immunosuppressant and azole antifungal agents being the most commonly involved drugs. The factor having the greatest influence on drug-drug interactions was a higher number of non-antineoplastic drugs.

Off-label prescription of drugs at hospital.

OBJECTIVES: To develop a procedure for management of off-label medications, and to analyze the treatments, indications, and hospital units which will request them more frequently, as well as which variables will have an impact on the authorization decision, and its economic impact. METHODS: A procedure was designed where clinicians would complete request forms and the Hospital Unit would prepare reports assessing their efficacy, safety, convenience, and cost. The request forms for the past five years were analyzed. RESULTS: A total of 834 applications were received, and 88.1% of these were accepted. The authorization rates were higher for Paediatric Units (95.7% vs. 86.6%; p<0.05). The reasons for considering prescriptions as off-label were: different indication (73.2%), different combination (10.2%), different line of treatment (8.6%) and different age (8%). A 73.4% of requests were for antineoplastic drugs, and the most frequently prescribed were rituximab (120) and bevacizumab (103). The quality of evidence supporting the prescriptions was moderate-low, though no direct relationship with the likelihood of approval was demonstrated (p = 0.413). The cost of the approved medications was 8,567,537 €, and the theoretical savings for those drugs rejected was of 2,268,642 €. There was a statistically significant decrease in the authorization rate (p < 0.05, Student's t test) when spending increased. CONCLUSIONS: The responsibility for assessing off-label prescriptions has fallen on the Pharmacy Unit. It has not been demonstrated that the quality of evidence represents a decisive variable for approval of treatment; on the other hand, age and cost have demonstrated a significant impact.

Objetivos: Desarrollar un proceso de gestión de medicamentos en condiciones fuera de ficha técnica y analizar los tratamientos, indicaciones y unidades clínicas que los solicitan, qué variables influyen en la decisión de autorización y su impacto económico. Métodos: Se diseñó un procedimiento según el cual los clínicos cumplimentarían las solicitudes, el Servicio de Farmacia redactaría los informes valorando su eficacia, seguridad, conveniencia y coste, y la dirección médica tomaría la decisión de aceptar o no su uso. Se analizaron las solicitudes de los últimos cinco años. Resultados: Se recibieron 834 solicitudes, autorizándose el 88,1%. Las tasas de autorización fueron mayores para los Servicios Pediátricos (95,7% frente a 86,6%; p < 0,05). Las razones por las que las prescripciones se consideraron fuera de ficha técnica fueron: diferente indicación (73,2%), combinación diferente (10,2%), línea diferente (8,6%) y edad diferente (8%). El 73,4% de las solicitudes fueron de antineoplásicos, siendo rituximab (120) y bevacizumab (103) los más prescritos. La calidad de la evidencia que avalaba las prescripciones fue moderada-baja, aunque sin demostrar relación directa con la probabilidad de aprobación (p = 0,413). El coste de los medicamentos aprobados fue de 8.567.537 € y el ahorro teórico de los denegados 2.268.642 €. El porcentaje de autorización disminuyó según aumentó el gasto de manera estadísticamente significativa (p < 0,05, test t de Student). Conclusiones: La responsabilidad de evaluación de las prescripciones fuera de ficha técnica ha recaído en los Servicios de Farmacia. La calidad de la evidencia no ha demostrado ser una variable decisiva para la aprobación de los tratamientos. En cambio, la edad y el coste sí que han demostrado influir significativamente.

Acquired haemophilia A in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribavirin: role of rituximab

Background: Acquired haemophilia is an uncommon condition caused by the development of clotting factor inhibitors. To eliminate them, immunosuppressive therapy with corticosteroids and cytotoxic drugs is required. Methods: We describe a case of rituximab use in acquired haemophilia refractory to conventional therapy in a 63 year old male patient with chronic hepatitis C virus infection who was receiving treatment with pegylated-interferon-α-2a plus ribavirin. Results: After 21 weeks of antiviral therapy, the patient was admitted to hospital with a large haematoma in the abdominal muscles. Factor VIII level was zero and inhibitor titer was 345 Bethesda units. Oral immunosuppressive therapy with methylprednisolone and cyclophosphamide was administered for 1 month, with limited improvement. Therefore, cyclophosphamide was replaced by a four once-weekly dose of intravenous rituximab. Two months later, factor VIII level was normal and inhibitor titer was undetectable. Conclusion: Rituximab may be useful for the treatment of acquired haemophilia resistant to standard therapy (AU)

Antecedentes: la hemofilia adquirida es un trastorno infrecuente causado por el desarrollo de inhibidores del factor de coagulación. Para eliminarlos, se requiere tratamiento con corticoides y fármacos citotóxicos. Métodos: Describimos el caso del uso de rituximab en hemofilia adquirida refractaria al tratamiento convencional en un hombre de 63 años con infección crónica por el virus de la hepatitis C y que estaba recibiendo tratamiento con interferón pegilado α-2a y ribarivina. Resultados: Tras 21 semanas de tratamiento antivírico, el paciente fue ingresado en el hospital por un gran hematoma en la musculatura abdominal. La concentración de factor VIII era nula y el título de inhibidor fue de 345 unidades Bethesda. Se administró tratamiento inmunosupresor oral con metilprednisolona y ciclofosfamida durante 1 mes, con escasa mejoría. Así pues, se sustituyó la ciclofosfamida por una dosis semanal de rituximab intravenoso. Dos meses después, la concentración de factor VIII se normalizó y el título de inhibidor era indetectable. Conclusión: Rituximab puede ser útil en el tratamiento de la hemofilia adquirida resistente al tratamiento estándar (AU)