The compatibility of a low concentration of hydrocortisone sodium succinate with selected drugs during a simulated Y-site administration.

Bolus dose concentrations of hydrocortisone (50mg/mL) are reported to be incompatible with midazolam and ciprofloxacin in Y-site mixing studies. We evaluated the physical and chemical compatibility of low concentrations of hydrocortisone sodium succinate (1 mg/ mL) with midazolam (1 mg/mL and 2mg/mL) and ciprofloxacin (2 mg/mL) solutions during a simulated Y-site administration study. The midazolam 1mg/mL, midazolam 2mg/mL and ciprofloxacin 2mg/mL solutions were individually combined with hydrocortisone sodium succinate 1mg/mL solution in a 1:1 ratio and tested in triplicate. Physical compatibility was evaluated using a previously described method immediately on mixing, after 60 minutes and after 120 minutes. Chemical compatibility was determined by measuring the hydrocortisone sodium succinate concentration of the test solutions 120 minutes after mixing compared with that of a reference sample of hydrocortisone sodium succinate solution. At all time points, when hydrocortisone was mixed with midazolam (1 mg/mL and 2mg/mL) and ciprofloxacin (2 mg/mL), the solutions remained clear, with no haziness, colour change, gas or precipitate formation, thus showing total physical compatibility. There were pharmacologically significant reductions (>10%) in measured hydrocortisone concentration (18.6% with midazolam 2mg/mL, P = 0.06; and 21.3% with ciprofloxacin, P = 0.01) in all of the test samples, as compared with the reference sample. According to currently recommended criteria, combining hydrocortisone sodium succinate at a concentration of 1mg/mL with a 1mg/mL solution of midazolam appears to be both chemically and physically compatible. However, mixing 1mg/mL hydrocortisone sodium succinate with 2mg/mL midazolam or with 2mg/ mL ciprofloxacin cannot be recommended.