Extended stability for diluted liposomal Vyxeos® infusions
GERPAC Congress 2026 highlights
Diluted infusions of CPX-351 (Vyxeos®) 0.6 mg/mL in 5% glucose remain physicochemically stable for 14 days refrigerated plus two days at room temperature, according to Helen Linxweiler (Department of Pharmacy, University Medical Centre of Johannes Gutenberg University, Mainz). This is far longer than the four hours stated in the Summary of Product Characteristics (SmPC).
Vyxeos is a liposomal formulation of cytarabine and daunorubicin used to treat acute myeloid leukaemia (AML). It is supplied as a lyophilisate. It is reconstituted with water for injection and diluted in 0.9% sodium chloride or 5% glucose (G5) before intravenous administration. According to the SmPC, the product is stable for 4 hours at 2–8°C after reconstitution, or 4 hours after reconstitution and dilution, plus a 90-minute infusion period. Such short shelf-lives limit the scope for advance preparation in centralised compounding units.
In this study, vials were reconstituted with 19 mL water for injection, giving 5 mg/mL cytarabine and 2.2 mg/mL daunorubicin. The solution was then diluted to 0.6 mg/mL in prefilled G5 infusion bags (n=3). Preliminary tests had shown rapid particle formation in 0.9% sodium chloride, so the study was carried out with G5 only. The bags were stored for 14 days at 2–8°C, followed by seven days at 25°C, and sampled at intervals throughout. The total amount of intact cytarabine and daunorubicin was measured by reverse -phase high -performance liquid chromatography (RP-HPLC). The free (non-encapsulated) fraction was determined by gel filtration followed by RP-HPLC. Particle size, size distribution and zeta potential were measured by dynamic light scattering.
Total concentrations of both drugs remained nearly unchanged over the entire storage period, well within the specification of at least 90% of the initial concentration. Leakage from the liposomes was greater for daunorubicin than for cytarabine. Free daunorubicin stayed below the 10% limit during refrigerated storage but rose once the bags were moved to 25°C. It exceeded the specification after two days at room temperature and reached around 13% by day 7. Free cytarabine remained below 3% throughout. The liposomes showed no signs of disintegration or aggregation: particle size stayed at about 120 nm, the polydispersity index stayed at 0.06–0.08 (specification below 0.2), and the zeta potential stayed between -54 and -62 mV.
The authors concluded that free daunorubicin is the stability-limiting parameter. Liposome stability was both temperature-dependent and concentration-dependent. At the lower concentration of 0.3 mg/mL, infusions remained stable for 14 days at 2–8°C but only one additional day at 25°C. The findings do not apply to 0.9% sodium chloride as the vehicle. To ensure both microbiological and physicochemical stability, Vyxeos/G5 infusion bags should be stored refrigerated.
Linxweiler H, Thiesen J, Krämer I. Physicochemical stability of CPX-351 (Vyxeos®) 0.6 mg/mL infusion solutions in prefilled 5% glucose infusion bags. Short communication. GERPAC Congress 2026.
Image: Helen Linxweiler
