Compatibility of argatroban with abciximab, eptifibatide, or tirofiban during simulated Y-site administration

Abstract

Purpose. The physical and chemical compatibility of argatroban with abciximab, eptifibatide, or tirofiban during simulated Y-site administration was studied. Methods. Test solutions of argatroban 1 mg/mL, abciximab 36 μg/mL, eptifibatide 2 mg/mL, and tirofiban 50 μg (as the hydrochloride salt) per milliliter in 5% dextrose injection (D5W) and in 0.9% sodium chloride injection (saline) were prepared in duplicate by using aseptic technique. Argatroban solution was mixed with abciximab, eptifibatide, or tirofiban solution, each at a ratio of 1:1 by volume, and at 4:1 with abciximab solution, 8:1 with tirofiban solution, and 16:1 with eptifibatide solution. Compatibility was evaluated immediately after solution preparation and after storage for four hours at 20–25 °C. Physical compatibility was determined with the unaided eye and with a particle counter, and chemical compatibility was measured with high-performance liquid chromatography. The chemical compatibility of argatroban and abciximab was not tested because of the poor stability or recovery of abciximab in the test diluents. Results. Argatroban was physically compatible with abciximab, eptifibatide, and tirofiban in D5W at each ratio tested and in saline at a 1:1 ratio. Argatroban was chemically compatible with eptifibatide and tirofiban. No significant impurities were detected, except for a single impurity in argatroban–eptifibatide 1:1 admixtures. Conclusion. At concentrations commonly used in practice, argatroban was physically compatible with abciximab and physically and chemically compatible with eptifibatide and tirofiban for four hours at 20–25 °C.