RESUMO
OBJECTIVE: To study the physicochemical and microbiological stability over 90â¯days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10â¯mg/mL eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3⯰C), at room temperature (25±2⯰C), and at 40⯰C (±2⯰C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30â¯days in open containers and up to 90â¯days in closed ones. RESULTS: The eye drops stored at 5⯰C were the most stable; in the 1â¯mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10â¯mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5⯰C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10â¯mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1â¯mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90â¯days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1â¯mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21â¯days under refrigeration, compared to 42â¯days for 10â¯mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7â¯days after opening.
Assuntos
Estabilidade de Medicamentos , Armazenamento de Medicamentos , Metilprednisolona , Soluções Oftálmicas , Conservantes Farmacêuticos , Soluções Oftálmicas/química , Metilprednisolona/administração & dosagem , Humanos , Contaminação de MedicamentosRESUMO
OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.
Assuntos
Estabilidade de Medicamentos , Armazenamento de Medicamentos , Metilprednisolona , Soluções Oftálmicas , Conservantes Farmacêuticos , Soluções Oftálmicas/química , Metilprednisolona/administração & dosagem , Humanos , Contaminação de MedicamentosRESUMO
OBJECTIVE: Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. METHOD: This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. RESULTS: The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. CONCLUSION: Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pneumopatias Fúngicas , Adulto , Criança , Humanos , Administração Intravenosa , Antifúngicos/efeitos adversos , Voriconazol/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Inhaled antibiotics have achieved or stabilised the clinical condition of patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. We aimed to determine the effectiveness of aztreonam lysine inhaled solution (AZLI) in patients with CF and chronic P. aeruginosa infection. METHODS: A retrospective observational study was conducted on patients with CF and chronic P. aeruginosa infection who received AZLI between July 2012 and September 2018 inclusive in three Spanish hospitals in a routine clinical practice setting. The primary endpoint was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) compared with the previous 12 months, at the start of AZLI treatment and 12 months after starting the drug. Other variables analysed were exacerbations, hospitalisations, type and route of antibiotics prescribed, weight and body mass index (BMI) and adverse drug reactions. RESULTS: In a cohort of 52 patients, AZLI treatment led to stabilisation of FEV1, changing from a mean (SD) value of 55.60 (21.3)% at the start of treatment to 56.8 (20.4)% after 12 months of treatment (p=0.5296) in patients who had not previously received the drug. In addition, it significantly reduced exacerbations from a median (P25; P75) of 2.0 (1.0; 3.0) in the 12 months prior to AZLI to 1.0 (1.0; 2.0) in the 12 months after treatment initiation (p=0.0350). AZLI also reduced the need for other antibiotics and prevented a decrease in BMI, with an adequate safety profile. CONCLUSIONS: AZLI achieved stabilisation of lung function measured by FEV1 in patients with CF and chronic P. aeruginosa infection, along with an adequate safety profile.
RESUMO
BACKGROUND: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. METHODS: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. RESULTS: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. CONCLUSION: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.
RESUMO
Background: Congenital nephrotic syndrome of the Finnish type (CNF) is a rare, severe glomerular disease caused by mutations in the NPHS1 gene, which codes for nephrin. It is characterised by massive proteinuria and severe edoema. Progression to end-stage kidney failure occurs during early childhood and the only curative treatment is kidney transplantation. Nowadays, patients need aggressive medical treatment, which includes daily albumin infusions (for months) until they get clinical stability to receive transplant. Objective: In our paediatric hospital, we implemented a multidisciplinary program for the home infusion of albumin with outpatient follow-up. The aim of the study was to assess the safety and efficacy of this program for the first four years of its implementation. Material and Methods: Retrospective observational study of CNF paediatric patients treated with home albumin infusion therapy from March 2014 to July 2018 at a tertiary care paediatric hospital. Information on albumin administration was obtained from the electronic prescription assistance program and details on clinical and care-related variables from the hospital's electronic information systems. Results: Four patients with CNF received albumin infusions for 18, 21, 22 months, and 3 years. The treatment was safe, and the complication rates were to be expected considering the severity of disease. Patients required a median of two hospital admissions a year (19 in total); 47% due to catheter-related complications, but there were just three catheter infections. Conclusions: In our experience, home albumin infusion therapy is safe and effective and helps to improve children health and quality of life.
RESUMO
As in other areas of the health system, COVID-19 has had a dramatic impact on hospital compounding. This area has faced numerous challenges, including the shortage of frequent-use products (hydroalcoholic solutions, lopinavir/ritonavir suspension), the use of new preparations for SARS-CoV-2 (tocilizumab, remdesivir), or requests from overwhelmed wards unable to assume the safe preparation of a high volume of medications (intravenous solutions). The demand for all types of preparations (topic and oral medications, intravenous solutions) has increased dramatically. This increase has highlighted the shortage of resources allocated to this area, which has made it difficult to meet the high demand for preparations. In addition, the pandemic has revealed the scarcity of research on such basic aspects as agent stability and drug compatibility. One of the most relevant conclusions drawn from the COVID-19 pandemic is that the basic areas of hospital pharmacy, along with other, must be maintained and reinforced, as these are the areas that make us essential.
Como todo el sector sanitario, la farmacotecnia hospitalaria ha sufrido el impacto de la pandemia de la COVID-19, enfrentándose a la necesidad de cubrir el desabastecimiento de productos de uso frecuente (soluciones hidroalcohólicas, lopinavir/ritonavir suspensión), a nuevas preparaciones surgidas de las nuevas necesidades provocadas por el SARS-CoV-2 (tocilizumab, remdesivir), o a peticiones de plantas desbordadas por la carga asistencial, incapaces de asumir con un mínimo de seguridad la preparación de numerosos medicamentos (mezclas intravenosas). El incremento de actividad ha sido en todo tipo de preparados (tópicos, orales y mezclas intravenosas) y ha puesto de manifiesto la escasez de recursos destinados a esta área, que se ha traducido en serios problemas para afrontar todas las elaboraciones necesarias, así como la falta de investigación en aspectos tan básicos como la estabilidad o la compatibilidad de medicamentos. Probablemente, una de las conclusiones más importantes que podemos extraer tras la COVID-19 es que sin menospreciar otras áreas de la farmacia hospitalaria que también deben desarrollarse debemos mantener y potenciar las áreas básicas de nuestra profesión. Aquellas que nos hacen imprescindibles.
Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Composição de Medicamentos , Pandemias , Serviço de Farmácia Hospitalar/organização & administração , Pneumonia Viral/tratamento farmacológico , Administração Oral , Antivirais/provisão & distribuição , Antivirais/uso terapêutico , Transfusão de Componentes Sanguíneos , COVID-19 , Desinfecção , Vias de Administração de Medicamentos , Interações Medicamentosas , Estabilidade de Medicamentos , Contaminação de Equipamentos/prevenção & controle , Excipientes , Previsões , Serviços de Assistência Domiciliar , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/química , Infusões Intravenosas , Lopinavir/administração & dosagem , Equipamento de Proteção Individual/provisão & distribuição , Plasma Rico em Plaquetas , Ritonavir/administração & dosagem , SARS-CoV-2 , Soluções , Tratamento Farmacológico da COVID-19RESUMO
Objetivo la administración de voriconazol nebulizado implica ventajas, incluyendo la optimización de la penetración pulmonar y la reducción de los efectos adversos e interacciones; sin embargo, la evidencia sobre su utilización es escasa y no existen presentaciones comerciales específicas para nebulización. Nuestro objetivo es caracterizar las soluciones de voriconazol elaboradas para nebulización y describir su uso en nuestro centro. Método estudio observacional retrospectivo incluyendo pacientes que reciben voriconazol nebulizado para el tratamiento de enfermedades pulmonares (infecciones fúngicas o colonizaciones). La solución de voriconazol se preparó a partir de los viales comerciales para la administración intravenosa. Resultados el pH y la osmolaridad de las soluciones de voriconazol fueron adecuados para su nebulización. Se incluyeron 10 pacientes, 9 adultos y un niño. La dosis fue de 40 mg en los adultos y 10 mg en el paciente pediátrico, diluido a 10 mg/ml, administrados cada 12-24 horas. La duración mediana del tratamiento fue de 139 (rango: 26-911) días. No se reportaron efectos adversos y no se detectó voriconazol en plasma cuando se administró únicamente vía nebulizada. Conclusiones la nebulización de voriconazol es bien tolerada y no se absorbe hacia la circulación sistémica. Son necesarios más estudios de investigación para evaluar su eficacia (AU)
Objective Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. Method This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. Results The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. Conclusion Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy (AU)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Pneumopatias Fúngicas/tratamento farmacológico , Voriconazol/administração & dosagem , Antifúngicos/administração & dosagem , Nebulizadores e Vaporizadores , Aspergilose Pulmonar/tratamento farmacológico , Resultado do Tratamento , Estudos RetrospectivosRESUMO
CASE: A child with Niemann-Pick disease type C was started on miglustat therapy at the age of 2â years. Intrathecal administration of hydroxypropyl-ß-cyclodextrin was added 5â months later. The initial dose of 175â mg was gradually increased over the first 6â months to reach 325â mg. The drug was administered every 15â days, and the patient received 43 doses. A slight delay in progression of the disease was seen during the first year of intrathecal hydroxypropyl-ß-cyclodextrin. However, additional symptoms have emerged since that time, suggesting a lack of effectiveness of the drug. Our patient has shown no drug-related adverse events. CONCLUSIONS: Intrathecal hydroxypropyl-ß-cyclodextrin therapy is safe, but its efficacy seems questionable in a patient with the severe infantile form of Niemann-Pick disease type C.
RESUMO
The oral administration of drugs to the pediatric population involves the extemporaneous preparation of liquid formulations. These formulations have studies on their physicochemical stability, but they often lack microbiological studies. The objective of this study is to check the microbiological quality of five oral liquid formulations prepared with different excipients, which represent five major combinations, in two conditions: kept unopened until the day of the test, and in a multi-dose vial opened daily. The formulations were prepared according to standard operating procedures. Half of each batch was packaged in vials that remained closed until the day of testing, and the other half in a single container which was opened daily. Both the vials and the containers had been previously sterilized. Microbiological tests were performed weekly during the first month of the study, and then every two weeks, until the expiration date. The microbiological quality of oral liquid formulations is determined by the Royal Spanish Pharmacopoeia. The conclusion was that none of the formulations prepared that were packaged in sterilized containers became contaminated, either in unopened vials or in multi-dose containers when they were opened daily.
La administración oral de fármacos a la población pediátrica implica la preparación de fórmulas líquidas extemporáneas. Estas fórmulas tienen estudios de estabilidad fisicoquímica pero en muchas ocasiones carecen de estudios microbiológicos. El objetivo del estudio es comprobar la calidad microbiológica de cinco fórmulas orales líquidas, preparadas con diferentes excipientes, que representan mayoritariamente cinco combinaciones, en dos condiciones: conservadas sin abrir hasta el día del análisis y abriendo diariamente el envase multidosis. Se prepararon las fórmulas según los procedimientos normalizados de trabajo. La mitad del lote de cada fórmula se envasó en viales que estuvieron cerrados hasta el día del análisis y la otra mitad en un solo frasco que se abría diariamente. Tanto los viales como los frascos para el envasado estaban esterilizados previamente. El análisis microbiológico se realizó cada semana durante el primer mes de estudio y después cada dos semanas hasta llegar al periodo de caducidad. La calidad microbiológica de las fórmulas orales líquidas viene marcada por la Real Farmacopea Española. Se concluye que ninguna de las fórmulas elaboradas envasadas en contenedores esterilizados se contaminó ni en los viales cerrados ni en los frascos multidosis cuando se abrieron diariamente.
Assuntos
Contaminação de Medicamentos , Pediatria/normas , Soluções Farmacêuticas/normas , Administração Oral , Adolescente , Carga Bacteriana , Criança , Composição de Medicamentos , Humanos , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
Como todo el sector sanitario, la farmacotecnia hospitalaria ha sufrido el impacto de la pandemia de la COVID-19, enfrentándose a la necesidad de cubrir el desabastecimiento de productos de uso frecuente (soluciones hidroalcohólicas, lopinavir/ritonavir suspensión), a nuevas preparaciones surgidas de las nuevas necesidades provocadas por el SARS-CoV-2 (tocilizumab, remdesivir), o a peticiones de plantas desbordadas por la carga asistencial, incapaces de asumir con un mínimo de seguridad la preparación de numerosos medicamentos (mezclas intravenosas). El incremento de actividad ha sido en todo tipo de preparados (tópicos, orales y mezclas intravenosas) y ha puesto de manifiesto la escasez de recursos destinados a esta área, que se ha traducido en serios problemas para afrontar todas las elaboraciones necesarias, así como la falta de investigación en aspectos tan básicos como la estabilidad o la compatibilidad de medicamentos. Probablemente, una de las conclusiones más importantes que podemos extraer tras la COVID-19 es que -sin menospreciar otras áreas de la farmacia hospitalaria que también deben desarrollarse- debemos mantener y potenciar las áreas básicas de nuestra profesión. Aquellas que nos hacen imprescindibles
As in other areas of the health system, COVID-19 has had a dramatic impact on hospital compounding. This area has faced numerous challenges, including the shortage of frequent-use products (hydroalcoholic solutions, lopinavir/ritonavir suspension), the use of new preparations for SARS-CoV-2 (tocilizumab, remdesivir), or requests from overwhelmed wards unable to assume the safe preparation of a high volume of medications (intravenous solutions). The demand for all types of preparations (topic and oral medications, intravenous solutions) has increased dramatically. This increase has highlighted the shortage of resources allocated to this area, which has made it difficult to meet the high demand for preparations. In addition, the pandemic has revealed the scarcity of research on such basic aspects as agent stability and drug compatibility. One of the most relevant conclusions drawn from the COVID-19 pandemic is that the basic areas of hospital pharmacy, along with other, must be maintained and reinforced, as these are the areas that make us essential
Assuntos
Humanos , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Composição de Medicamentos , Pandemias , Serviço de Farmácia Hospitalar/organização & administração , Pneumonia Viral/tratamento farmacológico , Antivirais/provisão & distribuição , Antivirais/uso terapêutico , Transfusão de Componentes Sanguíneos , Vias de Administração de Medicamentos , Interações Medicamentosas , Estabilidade de Medicamentos , Contaminação de Equipamentos/prevenção & controle , Infusões Intravenosas , Lopinavir/administração & dosagem , Ritonavir/administração & dosagemRESUMO
The oral administration of drugs to the pediatric population involves the extemporaneous preparation of liquid formulations. These formulations have studies on their physicochemical stability, but they often lack microbiological studies. The objective of this study is to check the microbiological quality of five oral liquid formulations prepared with different excipients, which represent five major combinations, in two conditions: kept unopened until the day of the test, and in a multi-dose vial opened daily. The formulations were prepared according to standard operating procedures. Half of each batch was packaged in vials that remained closed until the day of testing, and the other half in a single container which was opened daily. Both the vials and the containers had been previously sterilized. Microbiological tests were performed weekly during the first month of the study, and then every two weeks, until the expiration date. The microbiological quality of oral liquid formulations is determined by the Royal Spanish Pharmacopoeia. The conclusion was that none of the formulations prepared that were packaged in sterilized containers became contaminated, either in unopened vials or in multi-dose containers when they were opened daily (AU)
La administración oral de fármacos a la población pediátrica implica la preparación de fórmulas líquidas extemporáneas. Estas fórmulas tienen estudios de estabilidad fisicoquímica pero en muchas ocasiones carecen de estudios microbiológicos. El objetivo del estudio es comprobar la calidad microbiológica de cinco fórmulas orales líquidas, preparadas con diferentes excipientes, que representan mayoritariamente cinco combinaciones, en dos condiciones: conservadas sin abrir hasta el día del análisis y abriendo diariamente el envase multidosis. Se prepararon las fórmulas según los procedimientos normalizados de trabajo. La mitad del lote de cada fórmula se envasó en viales que estuvieron cerrados hasta el día del análisis y la otra mitad en un solo frasco que se abría diariamente. Tanto los viales como los frascos para el envasado estaban esterilizados previamente. El análisis microbiológico se realizó cada semana durante el primer mes de estudio y después cada dos semanas hasta llegar al periodo de caducidad. La calidad microbiológica de las fórmulas orales líquidas viene marcada por la Real Farmacopea Española. Se concluye que ninguna de las fórmulas elaboradas envasadas en contenedores esterilizados se contaminó ni en los viales cerrados ni en los frascos multidosis cuando se abrieron diariamente (AU)