Physical Compatibility of Pantoprazole with Selected Medications: DISCUSSION

This study has demonstrated that pantoprazole diluted in NS is physically compatible for up to 12 h at 23°C with 3.3% dextrose and 0.3% sodium chloride for injection and with 12 of 17 drugs diluted in D5W during simulated Y-site administration. Precipitation occurred with mixtures containing pantoprazole and dobutamine or norepinephrine. A colour change and a coloured precipitate were observed when pantoprazole was combined with esmolol, midazolam, or octreotide. The cause of the incompatibility between pantoprazole and these 5 drugs (esmolol, dobutamine, midazolam, norepinephrine, octreotide) may be due to the difference in pH between pantoprazole (pH greater than 8.0) and the other medications (pH less than 4.5).

The protocol used here for investigating potential concentration-dependent physical incompatibility involved an initial test of 9 concentration combinations of pantoprazole with a second drug. If the common method of mixing equal volumes of a more limited number of concentrations of each drug had been used in this study, pantoprazole might have been judged physically compatible with dobutamine, midazolam, octreotide, and norepinephrine. Protocols using limited concentration combinations fail to account for the possibility of a concentration-dependent incompatibility, as was observed in this study (Figures 1 to 5). These figures are similar to those developed by Henry and others5 for calcium salts in the presence of phosphate in total parenteral nutrition solutions; similar compatibility profiles have now been reported for numerous drug combinations.

These results are limited by a lack of chemical stability data. A physically compatible combination may be chemically incompatible, even in the absence of a colour change or the appearance of a precipitate. With 3 of the drugs tested in combination with pantoprazole (esmolol, midazolam, and octreotide) a change in colour was observed during the 12-h period after mixing, a likely indicator of a chemical change. In fact, in mixtures involving all 3 of these drugs a slight change in colour was observed within 15 min. Nonetheless, a clinically relevant degree of decomposition is unlikely to occur during the period of contact after mixing of 2 medications at a Y-site, since contact time in the shared tubing beyond the Y-site is generally extremely short. Viagra Online Canadian Pharmacy

Most Y-sites have less than 15 cm of tubing beyond the point of mixing, but even a relatively long IV tubing set (32 in. or 70 cm in length) of normal diameter will contain less than 2 mL of solution. Therefore, at usual flow rates for the adult clinical setting, the period of contact will be less than 2 or 3 min in most cases, even if the tubing is very long. Under these circumstances clinically important degradation is unlikely to occur. However, in some clinical situations, including pediatric practice or patients with extreme fluid restriction, lower flow rates could result in greater contact time. In situations where prolonged contact (more than 15 min) occurs between the point of first mixing and entry into the body, all drug combinations for which physical compatibility has been confirmed should ideally undergo chemical analysis with a stability-indicating method to confirm the stability of the combination.

Category: Drugs

Tags: compatibility, dobutamine, esmolol, midazolam, norepinephrine, octreotide, pantoprazole, Y-site

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