Physical Compatibility of Pantoprazole with Selected Medications: METHODS

Preparation of Test Mixtures of Drugs

Seventeen drugs (detailed in Table 1), each diluted in D5W at 3 different concentrations, were selected for visual compatibility testing with 3 concentrations of pantoprazole (0.16 mg/mL, 0.40 mg/mL, and 0.80 mg/mL) in NS. The 3 selected concentrations of each drug (noted in Table 1) represent the upper and lower limits of the range usually administered to adult patients and either a midpoint or the most commonly used concentration for adult clinical practice. The pantoprazole was prepared by first reconstituting a 40-mg vial of the drug (Pantoloc IV, lot 3011261; Altana Pharma Inc, Oakville, Ontario) with 10 mL of NS obtained from a 100-mL container of commercial NS (lot W2C06B3; Baxter Corporation, Toronto, Ontario). The reconstituted solution was further diluted with NS to prepare the 3 test solutions (0.16 mg/mL, 0.40 mg/mL, and 0.80 mg/mL). The 17 secondary drugs were initial­ly prepared in accordance with the manufacturer’s instructions and were further diluted in D5W to obtain the 3 test concentrations. To simulate the mixing of drugs during Y-site administration, a set volume (1 mL) of each drug at each concentration, as listed in Table 1, was combined with an equal volume (1 mL) of each concentration of pantoprazole in a clean, dry glass test tube. Thus, a total of 9 concentration combinations were prepared for each secondary drug with pantoprazole. In addition, a mixture of 3.3% dextrose and 0.3% sodium chloride for injection was also tested with the 3 concentrations of pantoprazole. To ensure thorough mixing, all test samples were agitated manually after being combined.

Determination of pH

The pH of each drug at each concentration to be tested was measured to the nearest 0.001 pH unit before the drug was mixed with pantoprazole. The pH meter (Accumet 925, Fisher Scientific, Nepean, Ontario) was standardized on each day on which pH was to be measured with commercially available buffer solutions (Fisher Scientific, Nepean, Ontario). The pH is reported to 2 decimal places.
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Table 1. Tested Concentrations and Initial pH of Medications before Mixing

Lower Limit of Usual

Mid-Range

Upper Limit of Usual

Range for Adult Use

Range for Adult Use

Drug

Manufacturer

Lot No.

Concentration Tested

pH

Concentration Tested

pH

Concentration Tested

pH


Pantoprazole


Altana Pharma Inc


3011261


0.16 mg/mL


8.02


0.40 mg/mL


8.06


0.80 mg/mL


8.25


2:1 NS-D5W
mixture


Baxter Corporation


W2D30A1


4.60


Ampicillin


Novopharm


112123


10 mg/mL


7.89


25 mg/mL


8.11


40 mg/mL


8.32


Cefazolin


Novopharm


3600400


20 mg/mL


4.52


30 mg/mL


4.73


40 mg/mL


4.81


Ceftriaxone


Hoffmann- La Roche Ltd


B24001


20 mg/mL


6.64


30 mg/mL


6.86


40 mg/mL


6.99


Dimenhydrinate


Astra Pharma Inc


E737


0.50 mg/mL


6.34


0.75 mg/mL


6.40


1.00 mg/mL


6.46


Dobutamine


Eli Lilly


5MG15M


1.0 mg/mL*


3.39


2.5 mg/mL*


2.93


4.0 mg/mL*


2.89


Dopamine


Dupont Pharma


1012-07


0.8 mg/mL


4.89


2.0 mg/mL


4.57


3.2 mg/mL


4.31


Epinephrine


Abbott Laboratories


70005NJ


16 pg/mL


5.94


24 pg/mL


5.74


32 pg/mL


5.52


Esmolol


Baxter Corporation


1041-59A


10 mg/mL*


4.21


15 mg/mL*


4.34


20 mg/mL*


4.46


Furosemide


Sabex Inc


112117


1.0 mg/mL


6.51


1.5 mg/mL


6.71


2.0 mg/mL


6.87


Insulin


Eli Lilly


5MR67P


5.0 unit/L


6.64


27.5
unit/L


7.04


50.0
unit/L


7.11


Midazolam


Sabex Inc


110414


1.0 mg/mL*t


3.74


1.5 mg/mL*


3.44


2.0 mg/mL*


3.45


Morphine


Abbott Laboratories


74029NJ


1 mg/mL


4.75


5 mg/mL


4.59


10 mg/mL


5.56


Nitroglycerin


Sabex Inc


109932


100 pg/mL


6.37


250 pg/mL


6.29


400 pg/mL


6.27


Norepinephrine


Sabex Inc


109551


6 pg/mL


6.02


8 pg/mL


5.89


64 pg/mL*


3.43


Octreotide


Novartis Pharma


C1F02611


5.0 pg/mL*


3.49


7.5 pg/mL*


3.51


10.0
pg/mL*


3.54


Potassium chloride


Astra Pharma Inc


E671


0.02
mEq/mL


6.70


0.21
mEq/mL


7.18


4.00
mEq/mL


7.14


Vasopressin


Ferring Inc


0M527


0.4
unit/mL


5.53


0.7
unit/mL


5.66


1.0
unit/mL


4.66

Visual Inspection of Physical Compatibility

Immediately after mixing of each pantoprazole- drug combination, the mixture was inspected visually for particulate matter against a black and then a white background in diffuse fluorescent laboratory light. Each mixture was also inspected for changes in colour and clarity and for evolution of gas. These observations were repeated at 15 min and 1, 4, and 12 h after mixing. All mixtures were stored at room temperature (23°C) throughout the study.  pharmacy uk

For combinations that produced a change in colour or clarity and those in which a precipitate was observed, an expanded range of concentrations was prepared to evaluate the extent of the incompatibility. Physically compatible and incompatible combinations were plotted on a graph to determine the concentration of each drug at the interface between physical compatibility and incompatibility.

Category: Drugs

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

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