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Journal of Oncology Pharmacy Practice :... Mar 2021Calcium levofolinate (CaLev) for intravenous administration is commercially available as a powder that must be reconstituted for injection or reconstituted and then...
PURPOSE
Calcium levofolinate (CaLev) for intravenous administration is commercially available as a powder that must be reconstituted for injection or reconstituted and then diluted before administration. The lack of stability data on CaLev solutions renders necessary extemporaneous manual preparation, preventing the use of automated/semi-automated systems, with a consequent loss in terms of quality and safety.
METHODS
The present work assessed the chemical-physical and microbiological stability of CaLev prepared in sodium chloride 0.9%, glucose 5% and water for injections and stored in polyolefin/polyamide bags and polypropylene syringes at 2-8°C protected from light. For this purpose, we developed and validated a new rapid High Performance Liquid Chromatography with Ultra Violet Diode-Array Detection (HPLC-UV-DAD) method.
RESULTS
The samples tested were stable for 14 days, retaining >95% of their initial concentration and showing no change in colour, turbidity or pH. Microbiological tests performed on the samples were negative.
CONCLUSIONS
Our results confirmed the analytical stability of CaLev in NaCl 0.9%, glucose 5% and water for injection at concentrations used in clinical practice at our institute. This enables our centralized laboratory to organize the preparation of this drug in advance and the use of robots rather than manual preparation reduces the workload and the risk of preparation errors.
Topics: Chromatography, High Pressure Liquid; Drug Packaging; Drug Stability; Drug Storage; Glucose; Levoleucovorin; Nylons; Polyenes; Polypropylenes; Saline Solution; Syringes; Temperature; Water
PubMed: 32299315
DOI: 10.1177/1078155220918025 -
Clinical Pharmacology in Drug... Apr 2023The aim of this study was to compare the bioequivalence and safety of test preparation sodium levofolinate injection with reference preparations of calcium levofolinate...
The aim of this study was to compare the bioequivalence and safety of test preparation sodium levofolinate injection with reference preparations of calcium levofolinate for injection and sodium folinate for injection in China. A single-center, randomized, open-label, 3-period, crossover test was conducted on 24 healthy subjects. Plasma concentration of levofolinate, dextrofolinate, and their metabolites l-5-methyltetrahydrofolate and d-5-methyltetrahydrofolate were quantified by a validated chiral-liquid chromatography-tandem mass spectrometry method. All adverse events (AEs) were documented to evaluate safety as they occurred and evaluated descriptively. Pharmacokinetic parameters (maximum plasma concentration, time to maximum concentration, area under the plasma concentration-time curve over the dosing interval, area under the plasma concentration-time curve from time 0 to infinity, terminal elimination half-life, and terminal rate constant) of 3 preparations were calculated. A total of 8 subjects (10 cases) of AEs occurred in this trial. No serious AEs or unexpected serious adverse reactions were observed. Sodium levofolinate was bioequivalent to calcium levofolinate and sodium folinate in Chinese subjects, and the 3 preparations were all well tolerated.
Topics: Humans; East Asian People; Healthy Volunteers; Therapeutic Equivalency; Levoleucovorin; Leucovorin
PubMed: 36808267
DOI: 10.1002/cpdd.1223 -
BMC Cancer Feb 2023Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic... (Observational Study)
Observational Study
BACKGROUND
Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma.
METHODS
We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m), levo-leucovorin calcium (200 mg/m) and 5-FU (2400 mg/m) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated.
RESULTS
At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1-4.8) and 1.3 months (95% CI, 1.0-1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3-4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010-4.107; p = 0.047) and 2.471 (95% CI, 1.063-5.745; p = 0.036), respectively.
CONCLUSION
FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels.
Topics: Humans; Irinotecan; Retrospective Studies; Leucovorin; Oxaliplatin; Anorexia; Pancreatic Neoplasms; Fluorouracil; Antineoplastic Combined Chemotherapy Protocols; Adenocarcinoma
PubMed: 36809997
DOI: 10.1186/s12885-023-10654-3