Jean-Daniel Hecq

Long‐term stability of cefuroxime and cefazolin sodium in intravenous infusions

Cefazolin and cefuroxime sodium are often used as antibiotic infusions for hospitalized patients. Because advance preparation of these intravenous solutions is efficient, the stability of both antibiotics stored at 4 °C in polyvinyl chloride (PVC) bags was studied.

Implementation of a protocol for administration of vancomycin by continuous infusion: pharmacokinetic, pharmacodynamic and toxicological aspects.

Optimising antibiotic administration is critical when dealing with pathogens with reduced susceptibility. Vancomycin activity is dependent on the area under the concentration-time curve over 24 h at steady-state divided by the minimum inhibitory concentration (AUC/MIC), making continuous infusion (CI) or conventional twice daily administration pharmacodynamically equipotent. Because CI facilitates drug administration and serum level monitoring, we have implemented a protocol for CI of vancomycin by: (i) examining whether maintaining stable serum concentrations (set at 25-30 mg/L based on local susceptibility data of Gram-positive target organisms) can be achieved in patients suffering from difficult-to-treat infections; (ii) assessing toxicity (n = 94) and overall efficacy (n = 59); and (iii) examining the correlation between AUC/MIC and the clinical outcome in patients for whom vancomycin was the only active agent against a single causative pathogen (n = 20). Stable serum levels at the expected target were obtained at the population level (loading dose 20mg/kg; infusion of 2.57 g/24 h adjusted for creatinine clearance) for up to 44 days, but large intrapatient variations required frequent dose re-adjustments (increase in 57% and decrease in 16% of the total population). Recursive partitioning analysis of AUC/MIC ratios versus success or failure suggested threshold values of 667 (total serum level) and 451 (free serum level), corresponding to organisms with a MIC>1 mg/L. Nephrotoxicity potentially related to vancomycin was observed in 10% of patients, but treatment had to be discontinued in only two of them.

Effect of the freezing conditions and microwave thawing power on the stability of cefuroxime in dextrose 5% infusion polyolefin bags at 4 degrees C.

BACKGROUND Intravenous cefuroxime sodium solution could be prepared in advance by a centralized hospital pharmacy service to improve safety and time management. OBJECTIVE To investigate the effect of freezing and microwave thawing on the solution stability of cefuroxime. METHODS Cefuroxime 1.5 g in 100 mL of dextrose 5% in polyolefin bags was frozen individually (group A) or in one package (group B) for 98 days at −20 °C. The solutions were then thawed using microwaves at 270 (light cycle) or 800 watts (hard cycle) and stored at 4 °C. The cefuroxime concentration was measured by HPLC. Visual inspection was performed and pH was measured at that time. Stability of the solution was defined as a concentration remaining superior to 90% of the initial concentration by regression analysis. RESULTS No color change or precipitation in the solutions was observed. In group A, stability was at least 23 and 21 days after light and hard cycle thawing, respectively. In group B, stability was at least 21 and 18 days, respectively, with the pH increasing without affecting chromatographic parameters. CONCLUSIONS The optimal conditions for advance preparation of a solution containing cefuroxime 1.5% in dextrose 5% may be freezing of individual containers followed by a light cycle of microwave thawing.

Doxorubicin-loaded drug-eluting beads (DC Bead®) for use in transarterial chemoembolization: A stability assessment

Purpose: Evaluation of doxorubicin stability over time when stored into the DC Bead embolic agent, in various containers, which are used for the delivery of the doxorubicin-loaded beads to the patients for up to 14 days under refrigerated conditions. Methods: The doxorubicin was loaded through the ionic exchange mechanism into the calibrated polyvinyl alcohol-based hydrogel beads (DC Bead), with the loading process carried out either in the original DC Bead glass vials or within a polypropylene plastic syringe. The loaded samples were eluted at given time points and the extracted doxorubicin was analysed by high-performance liquid chromatography for concentration and chromatographic area response purity. Results: The variance on the doxorubicin concentration of the samples stored in the syringes under refrigerated conditions was less than 10% over the 14 days period. The chromatographic purity of doxorubicin eluted from the DC Bead in their primary glass vial packaging was measured at 99.7%. The dissolution test showed that the elution rate and amount recovered from samples stored in vials were statistically similar between Day 0 and Day 14. The chromatographic purity of the doxorubicin loaded into DC Bead in presence of non-ionic contrast medium was >99.0% for 7 days under refrigerated conditions. Conclusions: Doxorubicin-loaded DC Bead® are shown to have adequate physicochemical stability over a period of 14 days when stored in syringes or vials under refrigerated conditions for up to 14 days. The admixtures of doxorubicin-loaded beads with contrast medium are stable for up to 7 days under refrigerated conditions.

Effect of Freezing, Long-Term Storage, and Microwave Thawing on the Stability of Ketorolac Tromethamine

BACKGROUND: Ketorolac tromethamine is a nonsteroidal agent with potent analgesic and moderate antiinflammatory activity. Advance preparation of intravenous solution could be useful to improve quality assurance, time management, and cost-savings of drug delivery. Objective: To investigate the effect of freezing, long-term storage, and microwave thawing on the stability of ketorolac tromethamine in dextrose 5% infusion. METHODS: Five polyolefin bags of solution containing ketorolac tromethamine 20 mg per 100 mL of dextrose 5% were frozen for 3 months at −20 °C, thawed in a microwave oven with a validated cycle, and stored at 4 °C. The concentration of ketorolac was measured by HPLC. Visual inspection and pH measurement were also carried out. RESULTS: No color change or precipitation was observed. Ketorolac was stable for at least 60 days under refrigeration after freeze–thaw. Throughout this period, the lower confidence limit of the estimated regression line of the concentration–time profile remained >90% of the initial concentration, and the pH value decreased slightly without affecting chromatographic parameters. CONCLUSIONS: Within these limits, ketorolac tromethamine in dextrose 5% infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.

Long-term stability of vancomycin hydrochloride in intravenous infusions.

Background and objective: Vancomycin is often used in antibiotic infusions for hospitalized patients and it is advantageous to prepare such intravenous solutions in advance. The objective of this study was to investigate the long‐term stability of this antibiotic stored at 4 d̀C in polyvinyl chloride (PVC) bags.

Effect of freeze-thawing on the long-term stability of calcium levofolinate in 5% dextrose stored on polyolefin infusion bags.

Background:  Calcium levofolinate infusions could be prepared in advance by a centralized intravenous additive service (CIVAS) to improve safety and time management.

SFPO and ESOP recommendations for the practical stability of anticancer drugs: An update.

The recommendations for the practical stability of anticancer drugs published in 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparaginase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, temsirolimus).

Stability of Ondansetron and Dexamethasone Infusion upon Refrigeration

Ondansetron is a serotonin receptor antagonist used in the treatment of chemotherapy-induced emesis1; the addition of dexamethasone increases the antiemetic efficacy.2 Advance preparation of intravenous solutions by a centralized intravenous additive service might improve quality assurance.3 Two studies have reported the stability of ondansetron stored at −20 °C.4,5 Our study investigated the stability of the combination of ondansetron hydrochloride plus dexamethasone sodium phosphate in dextrose 5% in polyolefin bags after freezing, microwave thawing, and long-term storage at 5 ± 3 °C.

Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: A generic product versus the brand name.

INTRODUCTION The aim of the study was to investigate the long-term stability of acyclovir 5 mg/mL (a generic product versus the brand name) in NaCl 0.9% after storage at 5±3°C and to evaluate the influence of initial freezing and microwave thawing on this stability. METHODS Five bags of Acyclovir® Hospira 5 mg/mL (A) and five bags of Zovirax® GSK 5 mg/mL (B) were prepared under aseptic conditions and stored 3 months at -20°C, then thawed and stored 30 days at 4°C. Five bags of Acyclovir® 5 mg/mL (C) and five bags of Zovirax® 5 mg/mL (D) were also prepared under aseptic conditions and stored 30 days at 5±3°C. Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCl 12 M and NaOH 5 M before and after heating at 100°C was also performed. The concentrations were measured by HPLC-PDA. RESULTS The only one forced degradation test that yielded chromatograms with degradation products peak was the test with the acid solution heated at 100°C without interference with the native product. No significant change in pH values or optic densities were seen during the study for both products. No crystals were seen with the optic microscope during the study. Acyclovir® and Zovirax® solutions were stable for at least 21 days according to the FDA recommendations. Moreover, there was no statistical difference between regression lines of those two products and two storage conditions. CONCLUSION Under the conditions of this study, Acyclovir® 5 mg/mL in 100 mL of NaCl 0.9% infusion remains stable at least for 21 days at 5±3°C with or without freezing at -20°C during the three previous months. There is no statistical difference between the brand name and a generic product. Acyclovir may be prepared in advanced by a centralized intravenous additive service, frozen in polyolefin bags and microwave thawed before storage under refrigeration until 21 days.