Physicochemical stability of bortezomib solutions for subcutaneous administration.

For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.

Drug prescribing in patients with renal impairment optimized by a computer-based, semi-automated system.

BACKGROUND: According to several studies, despite of the existence of several published guidelines for dosing adjustments based on renal function, inappropriate prescribing is a common drug-related problem in inpatient care. OBJECTIVE: We developed and implemented a system for drug dosage adjustment integrated into the Hospital computer provider order entry system. This system allows pharmacists to identify patients with reduced renal function, identify medication orders that may require dosage modifications based on renal function, and generate an alert with a recommendation of specific dosage adjustment. Using the Summary of Product Characteristics and two drug databases (Micromedex 2.0® and Lexicomp®), specific dosage guidelines for drugs used in patients with renal impairment were established. SETTING: A 264-bed tertiary teaching hospital. METHODS: We performed a quasi-experimental, one-group, pretest-posttest study to assess the efficacy of this intervention program. We compared the differences between the frequency of appropriate orders pre- and post-test using the McNemar test. MAIN OUTCOME MEASURES: the frequency of appropriate orders before the recommendation (pre-test) and after the recommendation (post-test). RESULTS: Before the intervention, the frequency of appropriate prescribing based on renal function was 65 %. After the intervention, this frequency was 86 % (p < 0.001). The interventions were more frequent in the emergency department (45 %). The program required 30-45 min of pharmacist time per day. The average number of patients reviewed daily was 28. This study found that a computer-based, semi-automated drug-dosage program for renal failure patients was able to reduce the number of inappropriate orders due to renal insufficiency.

ABCB1 gene polymorphisms are associated with adverse reactions in fluoropyrimidine-treated colorectal cancer patients.

AIM: To find out whether SNPs in the transporter gene ATP-binding casette B1 (ABCB1) were related to adverse effects in colorectal cancer patients treated with 5-fluorouracil (5-FU) or capecitabine. MATERIALS & METHODS: Patients treated with a 5-FU-based therapy (n = 67) or a capecitabine-based therapy (n = 74) were recruited and genotyped for the ABCB1 SNPs rs1128503 (C1236T), rs2032592 (G2677T/A) and rs1045642 (C3435T). Clinical data and adverse reactions were recorded. ABCB1 genotypes of patients were statistically analyzed for association with the most frequent adverse reactions. RESULTS: Statistical associations were observed, suggesting a lower risk of neutropenia (p = 0.013) and hand-foot syndrome (HFS; p = 0.027) for the carriers of T variation for rs1128503 in capecitabine-treated patients, carriers of T variation for rs1045642 treated with capecitabine had a lower risk of HFS (p = 0.033), while those treated with 5-FU had a higher risk of diarrhea (p = 0.035), and carriers of T variation for rs2032592 treated with capecitabine were at less risk of developing HFS (p = 0.033). CONCLUSION: This is the first time evidence has been found of differing pharmacogenetic markers for capecitabine and 5-FU treatments. Genotyping of SNPs in the ABCB1 gene prior to chemotherapy administration could help reduce adverse reactions in colorectal cancer patients.

Rapid carvedilol up-titration in hospitalized patients with left ventricular systolic dysfunction--data from the Carvedilol in Hospital: Up-titration Limits after Acute Patients Admission registry.

BACKGROUND AND OBJECTIVE: The safety of rapid carvedilol up-titration in patients with depressed left ventricular ejection fraction (LVEF) is unknown. The aim of the present work was to assess whether carvedilol can be used safely and rapidly up-titrated before hospital discharge in patients with left ventricular systolic dysfunction, with or without heart failure symptoms. METHODS: We studied 611 patients with LVEF less than 0.4 in whom carvedilol was used during hospital admission. RESULTS: Mean age was 66 years, 23% were women and 372 had symptoms of heart failure. Carvedilol was initiated 3 days after admission (median); 594 patients (97%) were discharged alive, 27 (5%) without beta-blockers. Carvedilol up-titration during admission was performed in 65%. The mean time of up-titration was 1 week, with a mean increase of 16 mg/day. The discharge dose was higher in younger patients and in those weighing more than 70 kg. Only 30 patients (5%) were re-admitted during the first month after discharge. At the end of follow-up (mean 2.3 years), 497 patients were alive and transplant-free (81%). Carvedilol mean daily dose at the end of follow-up was 32.4 +/- 22.2 mg and was related to the discharge dose. The absence of beta-blocker treatment at discharge was the most important independent predictor of long-term mortality (hazard ratio 3.1, 95% confidence interval 1.5-6.2, P = 0.002). CONCLUSION: Carvedilol up-titration is well tolerated in patients hospitalized with depressed LVEF, with or without heart failure, with a high compliance rate at discharge and in the long term.

Rapid carvedilol up-titration in hospitalized patients with systolic heart failure.

To determine whether carvedilol can be safely up-titrated before hospital discharge, we studied 372 consecutive patients with systolic heart failure who were being treated with carvedilol. Carvedilol was initiated a median of 3 days after admission, with a mean starting dose of 12 mg. Up-titration was performed in 67% of patients, with a mean increase of 16 mg and a mean discharge daily dose of 23 +/- 17 mg. Mean daily dose at the end of follow-up was 35.3 +/- 25.3 mg and it increased with higher discharge dose.

Administración de medicamentos por vía oral. Interacciones medicamento - alimento / Oral drug administration: drug-food interactions

Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio activo la administración en relación con alimentos o productos medicinales y otros aspectos relacionados con la administración por vía oral. Resultados: se elabora una tabla informativa sobre un total de 28 principios activos. Discusión: Los farmacéuticos de hospital se han integrado recientemente en los equipos multidisciplinares y desde esta posición tienen la oportunidad de desarrollar diferentes programas de atención farmacéutica, educación sanitaria e información encaminadas a prevenir problemas relacionados con los medicamentos, aumentar su uso seguro y disminuir los riesgos asociados a cualquier tratamiento farmacológico. Las prescripciones médicas generalmente no indican el horario y la forma de administración de los medicamentos, dejando a enfermeros y enfermeras la responsabilidad de su organización. Por esto deben estar informados de cómo y cuándo se deben administrar los medicamentos, lo que permite garantizar su uso seguro y disminuir los riesgos asociados al tratamiento

Background: The easiest, safest and cheapest way to administrate drugs is by mouth (PO). Nevertheless, there may be interactions, either with other drugs or with food, which can modify efficacy and security of the drug itself. Objective: the development of a nursing information program about the administration of drugs PO. Method: we selected the most used drugs corresponding to the pediatric cardiology area, looking for the best administration possible with or without food or medicinal products, and any other aspect related to their administration PO. Results: we elaborate the following table with all the information collected. Discussion: hospital pharmacists have recently been integrated in the multidisciplinary team that take care of patients, and so now they have the opportunity of developing different pharmaceutical care programs, sanitary education and information focused on the prevention of medication errors, the secure use and the diminish of any risks associated to any pharmacological treatment. Medical prescriptions usually do not specify timetable of way of administration of drugs, letting nurses the responsibility of their organization. That is why they must be well informed of how and when drugs must be administrated, so we can improve the security and decrease the risks associated to them