Chlorothiazide sodium is supplied in vials containing lyophilized drug equivalent to 500 mg of chlorothiazide with mannitol 250 mg and sodium hydroxide to adjust the pH.3132; 3133 Each vial should be reconstituted with 18 mL of sterile water for injection to obtain an isotonic solution yielding a concentration of 28 mg/mL of drug.3132; 3133 No less than 18 mL of sterile water for injection should be used for reconstitution.3132; 3133
pH
From 9.2 to 10.7
Trade Name(s)
Sodium Diuril
Chlorothiazide sodium is administered intravenously by direct injection or infusion.3132; 3133 It should not be administered intramuscularly or subcutaneously, and extravasation must be avoided.3132; 3133
Intact vials should be stored between 2 and 25°C3133 or between 20 and 25°C at controlled room temperature;3132 specific product labeling should be consulted for details. Vials are intended for single dose only and unused portions of the reconstituted solution should be discarded. The manufacturers state that the solution should be used immediately after reconstitution.3132; 3133 However, the reconstituted solution has been stated to be stable for 24 hours.7
Chlorothiazide sodium (APP) reconstituted with bacteriostatic water for injection, diluted in dextrose 5% to a chlorothiazide concentration of 10 mg/mL, and packaged as 10 mL in 15-mL polypropylene tubes (BD Biosciences) was physically compatible with less than 6% loss of chlorothiazide in 48 hours at 25°C in the dark.3568
pH Effects
Chlorothiazide sodium appears to be stable at pH 7.5 to 9.5 in dextrose 5%.7 No loss of potency was noted over a 24-hour study period.7
The solubility of chlorothiazide sodium is very pH sensitive.7 Depending on concentration, precipitation occurs at approximately pH 7.4 and below.7 Additives that result in a final pH in this range should not be mixed.7 Chlorothiazide sodium is sufficiently alkaline to raise the pH of unbuffered solutions such as dextrose, saline, and their combinations;7 however, if an acidic buffer is present, such as lactate or acetate buffers, the resultant pH may fall below pH 7.4, causing precipitation.7
Chlorothiazide sodium possesses some alkalizing power.7 Therefore, it should not be combined with drugs known to be unstable in alkaline media.7
Syringes
Chlorothiazide (APP) 25 mg/mL (as the sodium salt) diluted in sterile water for injection was packaged as 0.5 mL in 1-mL polypropylene syringes (Monoject) sealed with luer-tip caps (Becton Dickinson) and stored at 2 to 8°C protected from light for 10 days.3134 Neither changes in color or clarity nor appreciable changes in pH from baseline values occurred.3134 Samples exhibited a loss of approximately 8% by 6 days.3134
For a list of references cited in the text of this monograph, search the monograph titled References.