Stability of tedizolid phosphate-sodium rifampicin and tedizolid phosphate-meropenem admixtures in intravenous infusion bags stored at different temperatures.

This is a report on the chemical stability and physical compatibility of intravenous tedizolid phosphate 0.8 mg/mL-sodium rifampicin 2.4 mg/mL and tedizolid phosphate 0.8 mg/mL-meropenem 4 mg/mL combinations in polypropylene 0.9% sodium chloride infusion bags stored at different storage conditions. Triplicate solutions of both admixtures were prepared in 0.9% sodium chloride polypropylene infusion bags and stored under light protection at room temperature (25±2 °C), refrigeration (2-8 °C) or freezing (-15 - -25 °C) conditions. The study was performed using a validated and stability-indicating liquid chromatography (LC) method. For both admixtures and for all storage conditions, at least 90% of the initial drug concentration of tedizolid phosphate remained unchanged throughout the entire study period. Stability of sodium rifampicin at 25±2 °C was determined to be seven hours and six days when it was stored at 2-8 °C. Under the same storage conditions, meropenem was stable for 12 h or 6 days, respectively. Under freezing conditions, sodium rifampicin was stable throughout all 28 days, while stability of meropenem was only 8 days. Solutions of 0.8 mg/mL tedizolid phosphate admixtured with 2.4 mg/mL rifampicin or 4 mg/mL meropenem, in polypropylene 0.9% sodium chloride infusion bags, are stable for at least 7 or 12 hours, respectively, when stored at 25±2 °C. When stored at 2-8 °C, stability was increased to 6 days for both admixtures.

[Comparative analysis of the safety of triple therapy with telaprevir between HCV monoinfected and HIV coinfected patients]. / Análisis comparativo de la seguridad de la triple terapia con telaprevir entre pacientes monoinfectados por VHC y coinfectados por VIH.

PURPOSE: To know the possible differences in the toxicity profile of triple therapy with telaprevir between monoinfected and coinfected patients. METHOD: A retrospective observational study (January 2012- November 2013) of patients with HCV genotype 1, both monoinfected and coinfected with HIV, who had completed 12 weeks of treatment with telaprevir. The necessary variables were collected to characterize patients and the treatment received. The classification was made according to the toxicity criteria of the Division of AIDS v.1.0. A descriptive and comparative statistical analysis using the SPSS v.15.0 software was performed. RESULTS: 100 patients were included, 41% coinfected with HIV. Cirrhosis rate was observed at higher coinfected patients (97.6% vs 52.5%, p <0.001). TOXICITY: increased incidence in coinfected hyperbilirubinemia (51.2% vs 27.1% p = 0.012). TOXICITY grades: no differences in mild-moderate toxicity were observed between the two groups,while severe hyperbilirubinemia was higher in coinfected (26.8% (39.9% vs 12.2% p = 0.003) was observed, and dose adjustment of ribavirin (64.4% vs 26.8% p <0.001) in monoinfected patients. CONCLUSIONS: The study shows a similar toxicity profile between the two groups except for hyperbilirubinemia appears greater in coinfected patients (possibly related to the use of atazanavir) and less use of exogenous erythropoietin and dose reduction of ribavirin in them.

Análisis comparativo de la seguridad de la triple terapia bcon telaprevir entre pacientes monoinfectados por VHC y coinfectados por VIH / Comparative analysis of the safety of triple therapyvwith telaprevir between HCV monoinfected and HIV coinfected patients

Objetivo: Conocer las posibles diferencias en cuanto al perfil de toxicidad de la triple terapia con telaprevir entre pacientes monoinfectados y coinfectados. Método: Estudio observacional retrospectivo (Enero 2012-Noviembre 2013) de los pacientes con VHC genotipo 1, tanto monoinfectados como coinfectados por VIH, que hubieran finalizado las 12 semanas de tratamiento con telaprevir. Se recogieron las variables necesarias para caracterizar a los pacientes, y aquellas referentes al tratamiento recibido. La clasificación de la toxicidad se realizó según criterios de la División del SIDA v.1.0. Se realizó un análisis estadístico descriptivo y comparativo empleando el programa SPSS v.15.0. Resultados: Se incluyeron 100 pacientes, 41% coinfectado con el VIH. Se observó una tasa de cirrosis hepática superior en pacientes coinfectados (97,6% vs 52,5% p < 0,001). Toxicidad: mayor incidencia hiperbilirrubinemia en coinfectados (51,2% vs 27,1% p = 0,012). Toxicidad por grados: no se observaron diferencias en la toxicidad leve-moderada entre ambos grupos, mientras que la hiperbilirrubinemia grave fue mayor enlos pacientes coinfectados (26,8% vs 3,4% p = 0,001). Se observó mayor empleo de eritropoyetina exógena (39,9% vs12,2% p = 0,003), y de ajuste de dosis de ribavirina (64,4% vs26,8% p < 0,001) en pacientes monoinfectados. Conclusiones: Se evidencia un perfil de toxicidad similar entre ambos grupos a excepción de la hiperbilirrubinemia que aparece en mayor grado en los pacientes coinfectados (posiblemente relacionada con el uso de atazanavir), y al menor empleode eritropoyetina exógena y de reducción de dosis de ribavirinaen los mismos

Purpose: To know the possible differences in the toxicity profile of triple therapy with telaprevir between monoinfected and coinfected patients. Method: A retrospective observational study (January 2012-November 2013) of patients with HCV genotype 1, both monoinfected and coinfected with HIV, who had completed 12 weeks of treatment with telaprevir. The necessary variables were collected to characterize patients and the treatment received. The classification was made according to the toxicity criteria of the Division of AIDS v.1.0. A descriptive and comparative statistical analysis using the SPSS v.15.0 software was performed. Results: 100 patients were included, 41% coinfected with HIV. Cirrhosis rate was observed at higher coinfected patients (97.6% vs 52.5%, p <0.001). Toxicity: increased incidence in coinfected hyperbilirubinemia (51.2% vs 27.1% p = 0.012). Toxicity grades: no differences in mild-moderate toxicity were observed between the two groups, while severe hyperbilirubinemia was higher in coinfected (26.8%vs 3.4% p = 0.001). Increased use of exogenous erythropoietin (39.9% vs 12.2% p = 0.003) was observed, and dose adjustment of ribavirin (64.4% vs 26.8% p <0.001) in monoinfected patients. Conclusions: The study shows a similar toxicity profile between the two groups except for hyperbilirubinemia appears greater in coinfected patients (possibly related to the use of at azanavir) and less use of exogenous erythropoietin and dose reduction of ribavirin in them

Seguridad en la práctica clínica de la triple terapia con telaprevir en la hepatitis C crónica / Safety in the clinical practica of the triple teraphy with telaprevir in chronic hepatitis C

Objetivos: Estudiar la seguridad de la triple terapia con telaprevir y el momento de aparición de las RAM en el tratamiento de la hepatitis C. Método: Estudio observacional retrospectivo (Enero 2012-Junio 2013) de los pacientes con VHC genotipo 1 que hubieran finalizado las 12 semanas de triple terapia con telaprevir. Se recogieron las variables necesarias para caracterizar a los pacientes, y aquellas referentes al tratamiento recibido. La clasificación de las RAM se realizó según criterios de la División del SIDA versión 1.0. Resultados: Se incluyeron 88 pacientes (78% hombres), 75% pacientes cirróticos. El 40,9% estaba coinfectado con VIH. Las principales RAM (incidencia > 40%) incluyendo todos los grados: toxicidad hematológica, cansancio, hiperuricemia, hiperbilirrubinemia y prurito. Las RAM graves (incidencia > 15%): trombocitopenia, anemia y neutropenia. El 3,4% presentó toxicodermia grave. El 51,1% requirió ajuste de dosis de ribavirina, 13,6% transfusiones de sangre, y 28,4% eritropoyetina exógena. El 8% requirió ingreso hospitalario motivado por la toxicidad del tratamiento. El tratamiento fue suspendido por toxicidad en el 6,8% de los pacientes: 3 por toxicodermia grave, 2 por toxicidad hematológica grave, y 1 por emesis grave. La trombocitopenia y la hiperbilirrubinemia se registraron de manera temprana en su mayor grado de toxicidad, mientras que el resto de RAM presentaron periodos de progresión más prolongados. Conclusiones: El estudio señala un perfil de toxicidad superior al descrito en los ensayos clínicos, principalmente en cuanto a toxicidad hematológica, y permite predecir un rango de tiempo de mayor probabilidad de aparición de las RAM (AU)

Purpose: To study the safety of triple therapy with telaprevir and the time of appearance of the RAM in the treatment of hepatitis C. Method: A retrospective observational study (January 2012-June 2013) of patients with HCV genotype 1 who had completed 12 weeks of triple therapy with telaprevir. The following variables were needed to characterize patients, and those relating to the treatment received. The classification of ADR was performed according to criteria of the SIDA Division 1.0. Results: We included 88 patients (78% male), 75% cirrhotic patients. 40.9% were coinfected with HIV. The main ADR (incidence > 40%) including all grades: haematological toxicity, fatigue, hyperuricemia, hyperbilirubinemia and pruritus. Serious ADR (incidence > 15%): thrombocytopenia, anemia and neutropenia. 3.4% had severe toxicodermia. 51.1% required ribavirin dose adjustment, blood transfusions 13.6%, and 28.4% exogenous erythropoietin. The 8% required hospitalization motivated by treatment toxicity. The treatment was stopped for toxicity in 6.8% of patients: 3 severe toxicodermia, 2 severe haematological toxicity, and 1 severe emesis. Thrombocytopenia and hyperbilirubinemia occurred at an early stage in its higher degree of toxicity, while the other ADR presented progression longer periods. Conclusions: The study shows a superior toxicity profile to that described in clinical trials, mainly with regard to hematologic toxicity, and predicts a time range of highest probability of occurrence of ADR (AU)

[Safety in the clinical practice of the triple therapy with telaprevir in chronic hepatitis C]. / Seguridad en la práctica clínica de la triple terapia con telaprevir en la hepatitis C crónica.

PURPOSE: To study the safety of triple therapy with telaprevir and the time of appearance of the RAM in the treatment of hepatitis C. METHOD: A retrospective observational study (January 2012- June 2013) of patients with HCV genotype 1 who had completed 12 weeks of triple therapy with telaprevir. The following variables were needed to characterize patients, and those relating to the treatment received. The classification of ADR was performed according to criteria of the SIDA Division 1.0. RESULTS: We included 88 patients (78% male), 75% cirrhotic patients. 40.9% were coinfected with HIV. The main ADR (incidence > 40%) including all grades: haematological toxicity, fatigue, hyperuricemia, hyperbilirubinemia and pruritus. Serious ADR (incidence > 15%): thrombocytopenia, anemia and neutropenia. 3.4% had severe toxicodermia. 51.1% required ribavirin dose adjustment, blood transfusions 13.6%, and 28.4% exogenous erythropoietin. The 8% required hospitalization motivated by treatment toxicity. The treatment was stopped for toxicity in 6.8% of patients: 3 severe toxicodermia, 2 severe haematological toxicity, and 1 severe emesis. Thrombocytopenia and hyperbilirubinemia occurred at an early stage in its higher degree of toxicity, while the other ADR presented progression longer periods. CONCLUSIONS: The study shows a superior toxicity profile to that described in clinical trials, mainly with regard to hematologic toxicity, and predicts a time range of highest probability of occurrence of ADR.

Objetivos: Estudiar la seguridad de la triple terapia con telaprevir y el momento de aparición de las RAM en el tratamiento de la hepatitis C. Método: Estudio observacional retrospectivo (Enero 2012- Junio 2013) de los pacientes con VHC genotipo 1 que hubieran finalizado las 12 semanas de triple terapia con telaprevir. Se recogieron las variables necesarias para caracterizar a los pacientes, y aquellas referentes al tratamiento recibido. La clasificación de las RAM se realizó según criterios de la División del SIDA versión 1.0. Resultados: Se incluyeron 88 pacientes (78% hombres), 75% pacientes cirróticos. El 40,9% estaba coinfectado con VIH. Las principales RAM (incidencia > 40%) incluyendo todos los grados: toxicidad hematológica, cansancio, hiperuricemia, hiperbilirrubinemia y prurito. Las RAM graves (incidencia > 15%): trombocitopenia, anemia y neutropenia. El 3,4% presentó toxicodermia grave. El 51,1% requirió ajuste de dosis de ribavirina, 13,6% transfusiones de sangre, y 28,4% eritropoyetina exógena. El 8% requirió ingreso hospitalario motivado por la toxicidad del tratamiento. El tratamiento fue suspendido por toxicidad en el 6,8% de los pacientes: 3 por toxicodermia grave, 2 por toxicidad hematológica grave, y 1 por emesis grave. La trombocitopenia y la hiperbilirrubinemia se registraron de manera temprana en su mayor grado de toxicidad, mientras que el resto de RAM presentaron periodos de progresión más prolongados. Conclusiones: El estudio señala un perfil de toxicidad superior al descrito en los ensayos clínicos, principalmente en cuanto a toxicidad hematológica, y permite predecir un rango de tiempo de mayor probabilidad de aparición de las RAM.