Extended physicochemical stability of ready-to-administer fosnetupitant/palonosetron infusion solutions and...

Akynzeo 235 mg/0.25 mg concentrate for solution for infusion contains a fixed-dose combination of fosnetupitant (FNET) and palonosetron (PAL). Prior to administration, the Akynzeo concentrate (20 mL vial) is diluted with 30 mL 0.9% sodium chloride infusion solution (NS). According to the Summary of Product Characteristics, ready-to-administer (RTA) infusion solutions are physicochemically stable for 24 hours stored at room temperature. The aim of the study was to investigate the extended stability of FNET/PAL infusion solutions in polyolefin (PO) infusion bags as well as admixtures with 12 mg dexamethasone (DEX) injection solution, diluted with NS and stored at 25°C.

FNET/PAL (Akynzeo) and FNET/PAL/DEX test solutions were prepared in triplicate in PO bags prefilled with 30 mL and 100 mL NS and stored protected from light at 25°C in a climate chamber for 28 days. Directly after preparation, on day 1, 2, 3, 5, 14 and 28, test solutions were inspected visually and samples were withdrawn. FNET, PAL and DEX concentrations were determined simultaneously by a newly developed and validated stability-indicating high-performance liquid chromatography assay. In parallel, pH values were measured. Subvisible particles were counted on day 5.

Over the 28-day period, FNET and PAL concentrations remained above 99% and above 98% of the initially measured concentrations, respectively. Admixed with DEX, the concentrations of FNET, PAL and DEX remained above 99% of the initially measured concentrations. Results of pH measurement and visual inspection substantiated stability of the test solutions. Subvisible particle counts measured on day 5 of storage fulfilled the specifications of European Pharmacopoeia (Ph. Eur.) 2.9.19.

Reconstituted FNET/PAL (Akynzeo) infusion solutions and FNET/PAL/DEX admixtures diluted with 30 mL and 100 mL NS in prefilled PO bags are physicochemically stable for at least 5 days (subvisible particle count specification fulfilled) and 28 days (subvisible particle count not tested) when stored light-protected at 25°C. Results allow pharmacy-based preparation of RTA FNET/PAL and RTA FNET/PAL/DEX infusion solutions in advance.