Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen

Passardi, Alessandro; Monti, Manlio; Donati, Caterina; Foca, Flavia; Pagan, Flavia; Rapposelli, Ilario Giovanni; Ruscelli, Silvia; Bartolini, Giulia; Valgiusti, Martina; Matteucci, Laura; Sullo, Francesco Giulio; Sbaffi, Stefania; Crudi, Laura; Frassineti, Giovanni Luca; Masini, Carla

doi:10.1002/onco.13762

Cited by 2 publications

(5 citation statements)

References 15 publications

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“…Sodium levofolinate (Na‐Lev) has similar pharmacological properties to calcium levofolinate (Ca‐Lev) 7,12 and had advantages over Ca‐Lev in terms of the preparation process and administration 10,13 . Ca‐Lev was the first‐line therapy regimen for colon cancers 7 .…”

Section: Figurementioning

confidence: 99%

“…However, Na‐Lev could be safely dosed with 5‐FU simultaneously without the above disadvantages 7 . Time of treatment could be shortened to 1 day with Na‐Lev compared to 2 days of FOLFOX‐4 (a chemotherapy regimen for gastric cancer) with Ca‐Lev, which showed higher efficacy, lower side effects, shorter dosing time, and better patient compliance 7,12,15 . A combination of Na‐Lev and 5‐FU showed synergistic actions, enhanced antitumor activity, and reduced toxicity, while Ca‐Lev had just an additive effect on 5‐FU activity 7,12 .…”

Section: Figurementioning

confidence: 99%

“…10,13 Ca-Lev was the first-line therapy regimen for colon cancers. 7 However, simultaneous infusion of 5-FU and calcium folinate (Ca-FA) mixed in the same infusion pump was much more likely hindered by crystallization of calcium salts, which eventually led to catheter obstruction and damage, 7,9,12,14 increasing the risk of bacterial infection during surgery. 7 However, Na-Lev could be safely dosed with 5-FU simultaneously without the above disadvantages.…”

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confidence: 99%

“…7 Time of treatment could be shortened to 1 day with Na-Lev compared to 2 days of FOLFOX-4 (a chemotherapy regimen for gastric cancer) with Ca-Lev, which showed higher efficacy, lower side effects, shorter dosing time, and better patient compliance. 7,12,15 A combination of Na-Lev and 5-FU showed synergistic actions, enhanced antitumor activity, and reduced toxicity, while Ca-Lev had just an additive effect on 5-FU activity. 7,12 Due to better safety and effectiveness and fewer disadvantages, Na-Lev showed a much better clinical application prospect.…”

mentioning

confidence: 99%

“…7,12,15 A combination of Na-Lev and 5-FU showed synergistic actions, enhanced antitumor activity, and reduced toxicity, while Ca-Lev had just an additive effect on 5-FU activity. 7,12 Due to better safety and effectiveness and fewer disadvantages, Na-Lev showed a much better clinical application prospect. 16 Ca-Lev and sodium folinate (Na-F) was already marketed in China, so the aim of this study was to find, using pharmacokinetic (PK) parameters as indicators, whether Na-Lev was equivalent to Ca-Lev or Na-F in Chinese volunteers.…”

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Three‐Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects

Qiu

Liu

Wang

et al. 2023

Clinical Pharm in Drug Dev

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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 singlecenter, 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.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Three‐Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects

Qiu

Liu

Wang

et al. 2023

Clinical Pharm in Drug Dev

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In vitro compatibility of admixture solutions of 5-fluorouracil and khapzory (disodium levofolinate) in a single infusion bag

Saeed

2024

J Oncol Pharm Pract

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Introduction First-line chemotherapy for metastatic colorectal cancer typically involves a fluoropyrimidine, like 5-fluorouracil (5-FU), along with a folate agent, levoleucovorin. However, calcium-based levoleucovorin with 5-FU necessitates sequential infusion due to incompatibility, leading to calcium carbonate precipitation and potential IV catheter occlusion. In contrast, sodium-based levoleucovorin (disodium levoleucovorin-Khapzory) exhibits higher solubility in the low pH environment of 5-FU, enabling combination within a single IV bag for simultaneous infusion. This study aims to assess the safety of combining different concentrations of disodium levoleucovorin with 5-FU to create a single IV admixture bag or single pump Y-site, without risk of precipitate formation and catheter occlusion. Methods Compatibility of admixture 5-FU and disodium levoleucovorin in a 0.9% sodium chloride IV bag was evaluated, focussing on clarity (suspension, precipitation, and haziness). Particulate matter analysis was conducted at 25°C/60% relative humidity, for 29 samples at five timepoints. Defined pass criteria included a minimum of 6000 particles ≥10 µm per container and 600 particles ≥25 µm. Results All prepared concentrations remained clear for up to 72 h with no observed suspension, precipitation or haziness at any concentration or time point. Conclusions Combining 5-FU and disodium levoleucovorin in admixture IV bags eliminates the risk of catheter occlusion associated with calcium-based levoleucovorin formulations. This approach offers a more favorable operational and safety profile, enhancing convenience for patients and cost-efficiency for institutions.

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Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen

Cited by 2 publications

References 15 publications

Three‐Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects

Three‐Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects

In vitro compatibility of admixture solutions of 5-fluorouracil and khapzory (disodium levofolinate) in a single infusion bag

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