Visual compatibility of Vyxeos® during Y-site administration with selected drugs

G. Sicard1, M. Donnette1, N. Martin2, S. Gensollen2, R. Fanciullino1,2 1 SMARTc, CRCM, UMR Inserm 1068, CNRS UMR 7258, Aix Marseille Université U105, Faculté de Pharmacie, Marseille
2 Pharmacie, Hôpital de la Conception, Marseille

Introduction
Vyxeos® 44mg/100mg is a daunorubicine and cytarabine liposome indicated in patient newly diagnosed with acute myeloid leukemia (t-AML) or acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC). 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. Since February 2019, 7 patients have been treated by Vyxeos®) in the hematology department. These patients were all polymedicated and received complex infusion increasing the risk of the appearance of Y site incompatibilities. However, there is a lack of data on Y site compatibility of Vyxeos®) with others drugs while these phenomena are well described with cytarabine and daunorubicine.
The aim of this study is to evaluate the visual Y site compatibility of Vyxeos®) with selected drugs.

Methods
33 drugs were tested. Y-site evaluation was accomplished by mixing 2 mL of Vyxeos®) (in NaCl 0.9% final concentration 0.4 mg/mL) and 2 mL of tested drugs. Medication mixtures were analysed immediately after contact (T=0) and 90 minutes after, stored at room temperature (25°C). The particle analyses were performed visually and by Dynamic Light Scattering (DLS). All the measures were realized in duplicate. Drugs couple were classified in three categories: compatible, incompatible and variable compatibility (when dubious phenomenon appears).

Results
Most of the test drugs were compatible with Vyxeos®). Three drugs exhibited visual incompatibilities with Vyxeos®) at T = 0 and T = 90 minutes: amikacin, vancomycin and trimethoprim-sulfamethoxazole. However seven drugs presented incompatibilities using LDS: amikacin, amiodarone, gentamicin, magnesium chloride, piperacillin-tazobactam, trimethoprim-sulfamethoxazole and vancomycin. The combination with heparin sodium presented conflicting data and thus classified as variable compatibility.

Discussion-Conclusion
Knowledge and management of Vyxeos® Y site compatibilities are a major challenge in pharmaceutical care. This study underlines the drugs who must not been Y site injected with Vyxeos®). Besides, the study shows that DLS method is a more discriminant method as compared with visual analysis to detect incompatibilities.

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