Resumen Objetivo: Realizar un consenso de expertos utilizando el método Delphi para la clasificación del potencial de daño tisular de los antineoplásicos que facilite la toma de decisiones ante una extravasación. Método: El panel de evaluadores estaba formado por siete farmacéuticos del grupo de trabajo de extravasaciones. Otro actuó como coordinador. Se revisó la probabilidad de daño tisular a partir de ocho documentos de referencia. Se clasificaron en cuatro categorías: vesicante, irritante de alto riesgo, irritante de bajo riesgo y no irritante. Se realizaron dos rondas; tras éstas los fármacos con consenso < 70% se discutieron en grupo de forma no anónima. Se analizó para cada ronda: la mediana del grado de consenso y ámbito intercuartílico (AIQ25-75), el grado de concordancia por categoría de daño tisular y el porcentaje de antineoplásicos con grado de consenso > 85% y del 100%. Se analizaron de forma separada los fármacos con discordancias de clasificación entre los documentos consultados. Se utilizó el programa estadístico SPSS v23.0. Resultados: Se evaluaron 71 antineoplásicos. En la primera ronda la mediana del grado de consenso fue 100% (AIQ25-75: 71,4-100,0%) y en la segunda ronda 100% (AIQ25-75: 85,7-100,0%). El porcentaje de antineoplásicos con consenso ≥ 85,7% aumentó del 66,7% al 85,9% en la segunda ronda. Para los 30 antineoplásicos con discrepancias entre los documentos revisados, el grado de consenso aumentó del 71,4% (AIQ25-75: 57,1-87,7%) al 100% (AIQ25-75: 85,7-100,0%) en la segunda ronda. El porcentaje de antineoplásicos con concordancia ≥ 85,7% pasó del 40,0% al 76,7%. Cuatro antineoplásicos presentaron consenso < 70%. La clasificación final incluyó 17 fármacos como vesicantes, 15 como irritantes de alto riesgo, 13 como irritantes de bajo riesgo y 26 como no irritantes. El grado de acuerdo final fue ≥ 85,7% en el 90,1% de los antineoplásicos y del 100% en el 74,6%. Conclusiones: En este área de escasa evidencia y variabilidad la metodología Delphi permite alcanzar un consenso de clasificación del riesgo de daño tisular que facilita la toma de decisiones. Aproximadamente para el 90% de los antineoplásicos el grado de concordancia alcanzado por el panel de expertos fue > 85%, y para el 74% de los antineoplásicos la concordancia fue del 100%, aportando una base sólida para las decisiones de manejo.

Abstract Objective: To reach at an expert consensus, using the Delphi method, for classifying the tissue-damaging potential of antineoplastic drugs, in order to facilitate the decision-making process in the event of extravasations. Method: The panel of expert evaluators was made up of seven pharmacists belonging to the working group on extravasations. Other member served as coordinator. The likelihood of tissue damage was reviewed on the basis of eight reference documents. Four categories of drugs were established: vesicant (V); high risk irritant (HRI); low risk irritant (LRI) and non-irritant (NI). Two rounds of surveys were performed. The drugs with an agreement of less than 70% after the two rounds were discussed non-anonymously by the group. For each of the rounds the following was analysed: median of the degree of consensus and the interquartile range (IQR25-75), degree of agreement by tissue damage category, and percentage of antineoplastics reaching a degree of consensus of over 85% and of 100%. Drugs whose classification differed in the various reference documents were assessed separately. SPSS v23.0 statistical software was used. Results: Seventy-one antineoplastics were evaluated. In the first round, the median for degree of consensus was 100.0% (IQR25-75: 71.4-100.0%). In the second round, the median was 100.0% (IQR25-75: 85.7-100.0%). The percentage of antineoplastics with a consensus of 85.7% or above increased from 66.7% to 85.9% in the second round. For the 30 antineoplastics whose values differed in the reference documents, the degree of agreement increased from 71.4% (IQR25-75: 57.1-87.7%) to 100.0% (IQR25-75: 85.7-100.0%) in the second round. The percentage of antineoplastics with a consensus of 85.7% or above increased from 40.0% to 76.7%. Four antineoplastics had a degree of agreement of less than 70.0%. The final classification of drugs per category, was: 17 vesicants; 15 HRI; 13 LRI; and 26 NI. The final degree of consensus was 85.7% or above for 90.1% of antineoplastics, and 100.0% for 74.6% of the same. Conclusions: In this area of scarce evidence and high variability, the Delphi method allows for consensus in classifying tissue damage risk, thus making it easier to reach clinical decisions. In approximately 90% of the antineoplastics, the degree of consensus reached by the expert panel was 85% or above. In 74% of the antineoplastics, it was 100%. This provides solid ground for management decisions.

This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.

Abstract Objective: This review was prepared to offer the most complete information about the use of ondansetron in parenteral admixtures with other drugs. Method: The search was done from September 2016 to April 2017 by using electronic databases Stabilis® and Micromedex® solutions, Medline/PubMed and Scholar Google searching publications about ondansetron stability in parenteral infusion when is administered by itself or with other medication. Results: 49 studies are included with a total of 53 drugs. 15 drugs were found compatible administered with ondansetron in a clinical routine concentration range in intravenous administration. Also, four ternary blends were found compatible and another one was incompatible. Otherwise, 38 drugs were found incompatible. Conclusions: Compatibility of ondansetron offers a broad number of options to be used to avoid nausea and vomiting symptoms in patients with other concomitant medication.

Resumen Objetivo: Esta revisión ha sido preparada para recopilar toda la información referente a la estabilidad del ondansetrón en mezclas parenterales junto a otros fármacos. Método: La búsqueda fue realizada entre septiembre de 2016 y abril de 2017 empleando bases de datos electrónicas como Stabilis® y Micromedex® solutions, Medline/PubMed y Google Académico buscando publicaciones sobre la estabilidad del ondansetrón para infusión vía parenteral cuando es administrado en monoterapia o en una mezcla con otros fármacos. Resultados: En este trabajo han sido incluidos 49 artículos con un total de 53 fármacos. 15 fármacos han sido descritos como compatibles con ondansetrón en concentraciones habituales en la clínica práctica para administración intravenosa. Además, cuatro mezclas ternarias han sido descritas como compatibles y una como incompatible. Por otro lado, 38 fármacos han sido descritos como incompatibles para su administración con ondansetrón. Conclusiones: La compatibilidad del ondansetrón ofrece un amplio rango de opciones para evitar los síntomas de náuseas y vómitos en pacientes con otra medicación concomitante.