Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions / Estabilidad química y compatibilidad física de meropenem en mezclas para infusión intravenosa continua y extendida

Introduction: Prolonged intravenous infusion of beta-lactams increase the clinical cure rate compared to conventional administration in critical or septic patients. This study aimed to determine chemical stability and physical compatibility of meropenem at conditions used in clinical practice to evaluate the stability of the preparation during its administration and the possibility of anticipated preparation. Methods: Admixtures in study were: (i) meropenem 6g in 0.9% sodium chloride (NS) in infusor of 2mL/h 50mL or 10mL/h 240mL; (ii) meropenem 1 or 2g in NS in infusion bag of 250mL. Temperatures of study were: (i) infusor: 4.5°C, 32°C or 12h at 4.5°C followed by 32°C; (ii) Infusion bag: 4.5°C, 24.5°C or 6h at 4.5°C followed by 24.5°C. Time of study was 5–6 days in infusor and 1 day in infusion bag. Chemical stability was evaluated by high performance liquid chromatography and physical compatibility by measuring pH and visual inspection. Results: Chemical stability and physical compatibility of meropenem in admixtures in infusors were reduced at high meropenem concentration and high temperature. Admixtures in infusion bag show chemical stability and physical compatibility for at least 1 day. Conclusion: Administration of meropenem 6g in infusion of 24h in 240mL of 0.9% NaCl in infusor of 10mL/h could be possible if the admixture is infused at 4.5°C. Extended infusion of meropenem 1 or 2g in 0.9% NaCl in infusion bag (250mL) in 3–4h is also feasible. Anticipated preparation of the admixtures in infusion bag is possible with a stability of 24h.(AU)

Introducción: La infusión intravenosa prolongada de beta-lactámicos aumenta la velocidad de curación clínica comparada con la administración convencional en pacientes críticos o sépticos. Este estudio tiene como objetivo determinar la estabilidad química y la compatibilidad física de meropenem en condiciones utilizadas en la práctica clínica para evaluar la estabilidad de la preparación durante su administración y la posibilidad de la preparación anticipada. Métodos: Las mezclas en estudio fueron: (I) meropenem 6g en cloruro sódico 0,9% (SN) en infusor de 2mL/h 50 mL o 10mL/h 240mL; (iii) meropenem 1 o 2g en SN en bolsa de infusión de 250mL. Las temperaturas de estudio fueron: (i) infusor: 4,5°C, 32°C o 12h a 4,5°c seguido de 32°C; (ii) bolsa de infusión: 4,5°C, 24,5°C o 6h a 4,5°c seguido de 24,5°C. El tiempo de estudio fue de 5-6 días en infusor y 1 día en bolsa de infusión. Se evaluó la estabilidad química mediante cromatografía líquida de alta resolución y la compatibilidad física por medida de pH e inspección visual. Resultados: La estabilidad química y la compatibilidad física de meropenem en las mezclas en infusores disminuyeron al aumentar la concentración de meropenem y la temperatura. Las mezclas en bolsas de infusión mostraron estabilidad química y compatibilidad física durante al menos 1 día. Conclusión: La administración de meropenem 6g en infusión de 24h en 240 mL de cloruro sódico 0,9% en infusor de 10ml/h podría ser posible si la mezcla es administrada a 4,5°C. La infusión extendida de 1 o 2g en cloruro sódico 0,9% en bolsa de infusión (250 mL) en 3-4h es también viable. Puede realizarse la preparación anticipada de mezclas de meropenem en bolsas de infusión con una estabilidad de 1 día.(AU)

Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions.

INTRODUCTION: Prolonged intravenous infusion of beta-lactams increase the clinical cure rate compared to conventional administration in critical or septic patients. This study aimed to determine chemical stability and physical compatibility of meropenem at conditions used in clinical practice to evaluate the stability of the preparation during its administration and the possibility of anticipated preparation. METHODS: Admixtures in study were: (i) meropenem 6g in 0.9% sodium chloride (NS) in infusor of 2mL/h 50mL or 10mL/h 240mL; (ii) meropenem 1 or 2g in NS in infusion bag of 250mL. Temperatures of study were: (i) infusor: 4.5°C, 32°C or 12h at 4.5°C followed by 32°C; (ii) Infusion bag: 4.5°C, 24.5°C or 6h at 4.5°C followed by 24.5°C. Time of study was 5-6 days in infusor and 1 day in infusion bag. Chemical stability was evaluated by high performance liquid chromatography and physical compatibility by measuring pH and visual inspection. RESULTS: Chemical stability and physical compatibility of meropenem in admixtures in infusors were reduced at high meropenem concentration and high temperature. Admixtures in infusion bag show chemical stability and physical compatibility for at least 1 day. CONCLUSION: Administration of meropenem 6g in infusion of 24h in 240mL of 0.9% NaCl in infusor of 10mL/h could be possible if the admixture is infused at 4.5°C. Extended infusion of meropenem 1 or 2g in 0.9% NaCl in infusion bag (250mL) in 3-4h is also feasible. Anticipated preparation of the admixtures in infusion bag is possible with a stability of 24h.

Utilidad de las concentraciones séricas de adalimumab como predictores de adherencia al tratamiento / Clinical utility of serum concentrations of adalimumab as predictor of treatment adherence

OBJETIVO: Evaluar la utilidad de la determinación de concentraciones séricas (Cs) de adalimumab (ADA) como factor predictor de la adherencia al fármaco medida a través de la tasa de posesión de medicación (TPM) y del test de Morisky Green (MG) en pacientes con enfermedades crónicas inflamatorias. MATERIAL Y MÉTODO: Diseño prospectivo, descriptivo de cohortes. CRITERIOS DE INCLUSIÓN: pacientes adultos con artropatías inflamatorias (AI) o enfermedad inflamatoria intestinal (EII) en tratamiento con ADA. Criterios de exclusión: pacientes con anticuerpos anti-ADA. VARIABLES: sexo, edad, diagnóstico, pauta posológica, Cs (μg/ml), TPM (TPM ≥ 80% adherentes), y resultado del test de MG (no adherente o adherente). El análisis estadístico se realizó mediante STATA v13.0. RESULTADOS: Cuarenta y cinco pacientes (23 mujeres) con edad de 52,22 (14,39) años, 17 EII (37,78%), 26 AI (57,78%) y 2 con ambas enfermedades (4,44%) tratados con ADA cada 14 días (42/45,93,33%) o cada 7 días (3/45;6,67%). Se detectaron Cs infraterapéuticas en el 22,22% pacientes (10/45): el 10% (1/10) se clasifican como no adherentes y el 90% (9/10) como adherentes según MG y TPM. La Cs con la TPM, así como los métodos indirectos entre sí (TPM y MG) presentaron un índice de acuerdo débil, siendo la asociación ligeramente superior al relacionar los métodos indirectos entre sí (0,244 vs. 0,378). CONCLUSIÓN: La determinación de Cs de ADA presenta, por sí sola, una utilidad limitada en la detección de pacientes no adherentes

OBJECTIVE: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. MATERIAL AND METHOD: Design a prospective descriptive cohort study. Inclusion criteria: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. Exclusion criteria: positive anti-adalimumab antibody. VARIABLES: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. RESULTS: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). CONCLUSION: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients

Clinical utility of serum concentrations of adalimumab as predictor of treatment adherence. / Utilidad de las concentraciones séricas de adalimumab como predictores de adherencia al tratamiento.

OBJECTIVE: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. MATERIAL AND METHOD: Design a prospective descriptive cohort study. INCLUSION CRITERIA: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. EXCLUSION CRITERIA: positive anti-adalimumab antibody. VARIABLES: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. RESULTS: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). CONCLUSION: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients.

Effectiveness and Safety of Switching from Innovator Infliximab to Biosimilar CT-P13 in Inflammatory Rheumatic Diseases: A Real-World Case Study.

OBJECTIVE: CT-P13 is a biosimilar with comparable pharmacokinetics, efficacy and safety to its reference product (RP), infliximab. Studies have shown that switching from RP to CT-P13 does not reduce the effectiveness or safety of treatment. METHODS: In this retrospective real-world study, patients with inflammatory diseases treated with RP were switched to CT-P13 (n = 7) or continued on RP (n = 6). Clinical outcomes were compared between groups after four treatment cycles. RESULTS: CT-P13 demonstrated comparable effectiveness to its RP. All patients who switched to the biosimilar maintained or improved their clinical response, including two who remained in remission and three who moved into remission. In the RP group, five patients maintained their clinical response, with one achieving remission. Safety profiles were similar between groups. CONCLUSIONS: CT-P13 was equally effective as infliximab RP in this real-world study. CT-P13 is a valid, lower-cost alternative for patients currently receiving RP.

Chemotherapy dose intensity reductions due to adverse drug reactions in an oncology outpatient setting.

OBJECTIVE: the aim of this study was to establish the incidence of adverse drug reactions (ADRs) that prevent administration of planned dose intensity antineoplastic chemotherapy in clinical practice. METHODS: a retrospective cohort study was made of adult oncology patients who received intravenous chemotherapy in an outpatient ward during 2005. Dose delays, dose reductions, dose omissions, or treatment discontinuations with respect to the planned chemotherapy regimen were obtained, and causes were evaluated to identify ADRs. RESULTS: a total of 532 patients were included, involving the administration of 631 chemotherapy regimens. The total number of cycles evaluated was 3553. The incidence of nonadherence to planned treatment due to ADRs was 12.9% cycles (95% CI: 11.8-14.0). Differences according to patient's age were found, patients younger than 65 years showed higher rates of nonadherence due to ADRs. Myelosuppression was the main cause of dose delays, and gastrointestinal and neurological toxicity were reported as the main causes of dose reductions. CONCLUSIONS: the incidence of ADRs preventing planned dose intensity administration has been estimated. Follow-up of nonadherence to antineoplastic chemotherapy prescriptions can be used to evaluate tolerance in the clinical setting. Continuous evaluation of security in clinical practice provides information on benefits outweighing the deleterious effects in specific patient populations where the available data are limited.