Stability and visual compatibility of daunorubicin and cytarabine during Y-site administration with selected drugs.

e15516 Background: Vyxeos is a daunorubicine plus cytarabine liposome indicated in adults patient with newly diagnosed acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and therapy-related AML (t-AML). The standard protocol is an induction phase on D1, D3 and D5 at 100 mg/m² (expressed in cytarabine) during 90 minutes followed by 2 consolidation cures at 65 mg/m² on D1 and D3. Data provided from manufacturer indicate stability over 4 hours for diluted solution of daunorubicine plus cytarabine. AML-Patients are all receiving complex infusion increasing the risk of Y site incompatibilities. However, there is a lack of data on Y site compatibility of daunorubicine plus cytarabine with others drugs while these phenomena are well described with cytarabine and daunorubicine. The aim of this study was to evaluate stability and container-content interaction over time and visual Y site compatibility with selected drugs. Methods: Physicochemical stability over time was evaluated by Dynamic Light Scattering (DLS) (particle size) and by LC-MS/MS analysis (determination of cytarabine concentration). Daunorubicine plus cytarabine diluted solutions in 0.9% NaCl, final concentration 0.17 mg/mL were stored at 4°C during this study. Container-content interaction was evaluated comparing glass bottle and free-PolyVinylChloride (PVC) bag. Regarding Y site compatibility, a total of 33 drugs were tested. Medication mixtures were analyzed immediately after contact (T=0) and 90 minutes after, stored at room temperature (i.e., 25°C). The particle analyses were performed visually and by DLS. Drugs couple were classified in three categories: compatible, incompatible and variable compatibility when dubious phenomenon was observed. Results: No significative difference was found over time (120h) in term of particle size and chemical stability of cytarabine encapsulated, regardless of the container. This suggests that stability of daunorubicine plus cytarabine could actually be much longer than manufacturer’s recommendations. Most of the tested drugs were compatible. Still, three drugs exhibited visual incompatibilities at T = 0 and T = 90 minutes. However seven drugs presented incompatibilities using LDS. Two combinations presented conflicting data and thus classified as variable compatibility. Conclusions: Polypharmacy is a major concern in AML patients and knowledge and management of daunorubicine plus cytarabine stability and Y site compatibilities are critical to ensure a maximum safety at bedside. At least 10 drugs frequently used in oncology present a variety of incompatibilities with daunorubicine plus cytarabine and therefore should not be co-administered on Y site.