Stability of Aprepitant Injectable Emulsion in Alternate Infusion Bags, in Refrigerated Storage, and Admixed with Dexamethasone and Palonosetron

Abstract

Purpose

The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other antiemetics.

Methods

A volume of 18 mL aprepitant injectable emulsion was added to infusion bags (either non-di-(2-ethylhexyl) phthalate [DEHP], polyvinyl chloride [PVC]-containing bags or non-DEHP, non-PVC bags) containing 100, 130, or 250 mL of 0.9% normal saline solution (NSS) or 5% dextrose in water (D5W). Bags were stored at controlled room temperature (20–25°C) for up to 12 hours or refrigerated (2–8°C) for up to 72 hours. Compatibility/stability was also assessed in admixtures combined with either dexamethasone or palonosetron. At specified time points, bags were tested for appearance, pH, assay for aprepitant (ie, percent label claim of aprepitant) and aprepitant-related substances, Z-average particle size, globule size distribution, particulate matter, and DEHP content (PVC bags). In separate analyses to assess microbial burden, bags containing aprepitant were inoculated with seven different organisms and assessed for microbial growth.

Results

There was no detectable impact on the physicochemical properties or potential to promote microbial growth of aprepitant when diluted with various amounts of either NSS or D5W and when admixed with either dexamethasone or palonosetron at room temperature for at least 6 hours or during refrigeration for up to 72 hours in either PVC- or non-PVC-containing bags.

Conclusion

Aprepitant-containing admixtures are stable under these conditions, a finding that may improve patient and provider convenience and reduce medication wastage.

Keywords:

• chemotherapy-induced nausea and vomiting
• di-(2-ethylhexyl) phthalate
• DEHP
• microbial growth
• physicochemical
• polyvinyl chloride
• PVC

Acknowledgments

Medical writing support was provided by Phillip Giannopoulos, PhD, and Bret Fulton, RPh, of SciStrategy Communications, and funded by Heron Therapeutics, Inc. Experimental work was performed by Kimeka Douglas, Sarah Goodnight, and Kevin Jones of Alcami (Wilmington, NC) and Elaine Cung of Analytical Lab Group (Acton, MA). Data aggregation was provided by Will Everett of Heron Therapeutics, Inc.

Abbreviations

5-HT₃, 5-hydroxytryptamine type 3; CFU, colony-forming unit; CINV, chemotherapy-induced nausea and vomiting; CRT, controlled room temperature; D5W, 5% dextrose in water; DEHP, di-2-ethylhexyl phthalate; DLS, dynamic light scattering; FDA, Food and Drug Administration; HEC, highly emetogenic chemotherapy; HPLC, high-performance liquid chromatography; IV, intravenous; LC, label claim; MEC, moderately emetogenic chemotherapy; MRSA, methicillin-resistant S. aureus; NDC, National Drug Code; NK-1, neurokinin-1; NSS, normal saline solution; PFAT5, percent of fat globules larger than 5 µm; PVC, polyvinyl chloride; RT, room temperature; SDA, Sabouraud dextrose sugar; VREF, vancomycin-resistant Enterococcus faecalis.

Disclosure

Thomas Ottoboni and Arlene Santhouse report employment by Heron Therapeutics, Inc. Laura Lerner was an employee for Heron Therapeutics, Inc. at the time the study was conducted. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by Heron Therapeutics, Inc., San Diego, CA, USA.