Physicochemical Stability Of Diluted “Akynzeo^®” Infusion Solutions In Prefilled 0.9% Sodium Chloride Infusion Bags

Background and importance
Akynzeo^® 235 mg/0.25 mg concentrate for solution for infusion contains a combination of fosnetupitant (FOS) and palonosetron (PAL). The medicine is indicated for prevention of acute and delayed chemotherapy-induced nausea and vomiting.
Prior to administration, the Akynzeo^® concentrate (20 mL vial) is diluted with either 30 mL or 100 mL 0.9% sodium chloride infusion solution. According to the SmPC, ready-to-administer (RTA) infusion solutions are physicochemically stable for 24 hours stored at room temperature. To our knowledge, extended stability data are not published yet.

Aim and objectives
Extended stability data of RTA FOS/PAL infusion solutions are prerequisite to implement an efficient pharmacy-based preparation in advance. To fill the gap of extended stability data, the physicochemical in-use stability of RTA FOS/PAL infusion solutions in polyolefin (PO) infusion bags stored at room temperature was investigated.

Materials and methods
RTA FOS/PAL test solutions were prepared in triplicate using prefilled 0.9% sodium chloride PO bags in order to achieve nominal concentrations of FOS 4.7 mg/mL/PAL 5 µg/mL (20 mL Akynzeo^® plus 30 mL 0.9% sodium chloride) and FOS 1.958 mg/mL/PAL 2.08 µg/mL (20 mL Akynzeo^® plus 100 mL 0.9% sodium chloride), respectively. Test solutions were stored protected from light at 25°C in a climate chamber for 14 days. Directly after preparation (h0), after 12 hours (h12), on day 1, 2, 3, 5, 14 test solutions were inspected visually and samples withdrawn. FOS and PAL concentrations were determined by a newly developed and validated stability-indicating HPLC method. In parallel, pH values were measured. Non-visible particles were counted on day 5 in accordance with Ph.Eur. 2.9.19.

Results
FOS concentrations remained above 99% and PAL concentrations remained above 98% of the initially measured concentrations over the 14-day observation period. Results of pH measurement and visual inspection indicated stability of the tests solutions. Non-visible particle counts measured on day 5 of storage fulfilled the specifications of Ph. Eur. 2.9.19.

Conclusion and relevance
RTA FOS/PAL (Akynzeo^®) infusion solutions diluted with 30 mL and 100 mL in prefilled 0.9% sodium chloride PO bags are physicochemically stable for at least 14 days when stored light protected at 25 °C. Results allow pharmacy-based preparation of RTA FOS/PAL infusion solutions in advance.

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