Compatibility of daptomycin with commercially available syringe filters.

Abstract

To the Editor: Cubicin (daptomycin for injection; Cubist Pharmaceuticals, Lexington, MA) is a cyclic lipopeptide antibacterial indicated in the United States for the treatment of complicated skin and skin structure infections and Staphylococcus aureus bloodstream infections, including those with right-sided infective endocarditis.1 Daptomycin’s prescribing information states that parenteral drug products should be inspected visually for particulate matter prior to administration, however, medical inquiries regarding the use of filters after reconstitution are common.1 Cubist conducted a study to evaluate the compatibility of reconstituted daptomycin with 5 commercially available syringe filters, based on comparison of both appearance and high-performance liquid chromatography (HPLC) potency of the filtered solution to an unfiltered control. Compatibility was defined for the filtered samples as no visible difference in the appearance versus the unfiltered control and no more than a 5% decrease in potency from the unfiltered control. Ten vials of daptomycin lot CDC079 were reconstituted with 10 mL of 0.9% sodium chloride for injection USP and pooled into a clear container. Fifteen milliliters of the pooled solution was first removed using an unfiltered syringe and transferred into a scintillation vial as a control sample. Utilizing a syringe with each of the syringe filters listed in Table 1, 15 mL of the pooled solution was withdrawn through the syringe. The filter was subsequently removed, and the filtered material was transferred into 1 of 5 scintillation vials. After visual inspection of each solution, the color and clarity of each were recorded and any discrepancy between the filtered solutions and the control solution was documented. Potency analysis was subsequently performed for each solution by reverse-phase HPLC using a C8 column, with a qualified daptomycin reference standard, lot 010903A. Table 1. Compatibility of daptomycin with selected syringe filters Analysis of the solutions demonstrated that the 5 filters tested did not impact the appearance of the solution (ie, no visual differences were observed between the filtered samples and the unfiltered control) or cause a significant decrease in potency (the percent difference from the control ranged from 0.39% to 2.23%, meeting the acceptance criteria defined in the protocol). All 5 filters evaluated in this study are considered compatible with reconstituted daptomycin.